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1.
Patel, Sarju.
Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction.
Degree: PhD, 2016, Worcester Polytechnic Institute
URL: etd-040416-140014
;
https://digitalcommons.wpi.edu/etd-dissertations/473 
► Copper and iron are trace elements that form an indispensable part of many proteins and are crucial for the well-being of all cells. At…
(more)
▼ Copper and iron are trace elements that form an indispensable part of many proteins and are crucial for the well-being of all cells. At the same time, the intracellular levels of these metals require careful regulation, as excess or deficiency may be lethal. P
1B-ATPases are key players in
metal homeostasis. They belong to the superfamily of P-type ATPases, transmembrane proteins present in virtually all life forms, are responsible for solute translocation across biological membranes. The goal of this thesis is to improve our understanding of the structural and functional roles of P
1B-ATPases in
metal homeostasis by focusing on the host-microbe interaction. The thesis first describes the importance of Cu
+ distribution in the outcome of host-microbe interaction. Copper is an important element in host-microbe interactions, acting both as a catalyst in enzymes and as a potential toxin. Cu
+-ATPases drive cytoplasmic Cu
+ efflux and protect bacteria against
metal overload. Many pathogenic and symbiotic bacteria contain multiple Cu
+-ATPase genes within particular genetic environments, suggesting alternative roles for each resulting protein. This hypothesis was tested by characterizing five homologous Cu
+-ATPases present in the symbiotic organism <I>Sinorhizobium meliloti</I>. Mutation of each gene led to different phenotypes and abnormal nodule development in the alfalfa host. Distinct responses were detected in free-living <I>S. meliloti</I> mutant strains exposed to
metal and redox stresses. Differential gene expression was detected under Cu
+, oxygen or nitrosative stress. These observations suggest that CopA1a maintains the cytoplasmic Cu
+ quota and its expression is controlled by Cu
+ levels. CopA1b is also regulated by Cu
+ concentrations and is required during symbiosis for bacteroid maturation. CopA2-like proteins, FixI1 and FixI2, are necessary for the assembly of two different cytochrome <I>c</I> oxidases at different stages of bacterial life. CopA3 is a phylogenetically distinct Cu
+-ATPase that does not contribute to Cu
+ tolerance. It is regulated by redox stress and required during symbiosis. We postulated a model where non-redundant homologous Cu
+-ATPases, operating under distinct regulation, transport Cu
+ to different target proteins. In its second part, the thesis describes the novel Fe
2+-ATPases and their influence in the host-microbe interaction. Little is known about iron efflux transporters in bacterial systems. Recently, the participation of <I>Bacillus subtilis</I> PfeT, a P
1B4-ATPase, in cytoplasmic Fe
2+ efflux has been proposed. We report here the distinct roles of mycobacterial P
1B4-ATPases in the
homeostasis of Co
2+ and Fe
2+. Mutation of <I>Mycobacterium smegmatis ctpJ</I> affects the
homeostasis of both ions. Alternatively, a <I>M. tuberculosis ctpJ</I>…
Advisors/Committee Members: Arne Gericke, Committee Member, José M. Argüello, Advisor, Robert E. Dempski, Committee Member, Reeta Prusty Rao, Committee Member.
Subjects/Keywords: Metal transport; Metal homeostasis; P1B-ATPase
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APA (6th Edition):
Patel, S. (2016). Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction. (Doctoral Dissertation). Worcester Polytechnic Institute. Retrieved from etd-040416-140014 ; https://digitalcommons.wpi.edu/etd-dissertations/473
Chicago Manual of Style (16th Edition):
Patel, Sarju. “Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction.” 2016. Doctoral Dissertation, Worcester Polytechnic Institute. Accessed January 21, 2021.
etd-040416-140014 ; https://digitalcommons.wpi.edu/etd-dissertations/473.
MLA Handbook (7th Edition):
Patel, Sarju. “Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction.” 2016. Web. 21 Jan 2021.
Vancouver:
Patel S. Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction. [Internet] [Doctoral dissertation]. Worcester Polytechnic Institute; 2016. [cited 2021 Jan 21].
Available from: etd-040416-140014 ; https://digitalcommons.wpi.edu/etd-dissertations/473.
Council of Science Editors:
Patel S. Functional Diversity of Homologous P1B-ATPases in Metal Homeostasis and Host-Microbe Interaction. [Doctoral Dissertation]. Worcester Polytechnic Institute; 2016. Available from: etd-040416-140014 ; https://digitalcommons.wpi.edu/etd-dissertations/473
Queen Mary, University of London
2.
Matheou, Christian James.
The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease.
Degree: PhD, 2015, Queen Mary, University of London
URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12901
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775159
► Alzheimer's disease is characterised by the misfolding and aggregation of a native peptide, Aβ, for which there are several isoforms, Aβ(1-40) being the most common,…
(more)
▼ Alzheimer's disease is characterised by the misfolding and aggregation of a native peptide, Aβ, for which there are several isoforms, Aβ(1-40) being the most common, and Aβ(1-42) being most closely associated with Alzheimer's disease. Upon misfolding, Aβ self-associates to form a number of aggregate species. What triggers this process of misfolding-aggregation, and determines which aggregate species forms, is not known. One possible determinant is metal homeostasis, which in Alzheimer's patients is deregulated. Chapter 3 characterises how physiologically relevant levels of Cu2+ influence the misfolding pathway of Aβ. A ThT fluorescence assay found that Cu2+ is able to accelerate formation of Aβ(1-40) amyloid fibres; however, for Aβ(1-42), Cu2+ abolished fibre formation. Electron microscopy revealed that this is because Cu2+ stabilised Aβ(1-42) oligomers. These oligomers more readily disrupted lipid membranes than mature amyloid fibres, suggesting that the elevated levels of Cu2+ and the greater Aβ(1-42) synaptotoxicity in Alzheimer's disease may be related. Chapter 4 investigates the effect of Zn2+ on Aβ misfolding. Trace levels of Zn2+ are demonstrated to entirely abolish fibre growth, for both Aβ(1-40) and Aβ(1-42). It is found that that Zn2+ likely exerts such a dramatic effect through a rapid exchange of Zn2+ between Aβ molecules. Chapter 5 found that Cu2+ accelerated Aβ(1-40) fibre growth regardless of growth conditions, despite growth conditions influencing fibril morphology. It was also found that Cu2+ generated Aβ(1-40) fibres did not exhibit an altered stability, further suggesting that the effect of Cu2+ upon Aβ(1-40) is limited to fibril growth kinetics, in contrast to the effect of Cu2+ on Aβ(1-42), as well as the effect of Zn2+ upon either peptide. The present research has identified a diversity of significant interactions between Aβ, and Cu2+ and Zn2+, highlighting a potential role for these metal ions in Alzheimer's disease.
Subjects/Keywords: Biological and Chemical Sciences; Alzheimer's; metal homeostasis
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APA (6th Edition):
Matheou, C. J. (2015). The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/12901 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775159
Chicago Manual of Style (16th Edition):
Matheou, Christian James. “The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease.” 2015. Doctoral Dissertation, Queen Mary, University of London. Accessed January 21, 2021.
http://qmro.qmul.ac.uk/xmlui/handle/123456789/12901 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775159.
MLA Handbook (7th Edition):
Matheou, Christian James. “The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease.” 2015. Web. 21 Jan 2021.
Vancouver:
Matheou CJ. The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2015. [cited 2021 Jan 21].
Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12901 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775159.
Council of Science Editors:
Matheou CJ. The influence of copper and zinc on the self-assembly of Amyloid-β from Alzheimer's disease. [Doctoral Dissertation]. Queen Mary, University of London; 2015. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12901 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775159
University of Melbourne
3.
Choo, Xin Yi.
Development of novel therapeutic approaches for treatment of Alzheimer's disease.
Degree: 2018, University of Melbourne
URL: http://hdl.handle.net/11343/216470
► AD is a complex disease, involving the perturbation of multiple interrelated biological pathways. Despite being the most common form of neurodegenerative disease, with the number…
(more)
▼ AD is a complex disease, involving the perturbation of multiple interrelated biological pathways. Despite being the most common form of neurodegenerative disease, with the number of patients expected to increase drastically, the aetiology of AD remains unknown. Although genetic factors such as mutations in the APP and PSEN genes, which drive the overproduction of Aβ, are known to cause early on-set familial AD (EOFAD), majority of AD patients (> 95%) who develop clinical symptoms of AD later in life (i.e. late on-set AD (LOAD)) do not carry these mutations. Contrary to earlier assumptions that occurrence of LOAD was sporadic, GWAS and exome sequencing studies have identified genetic variants, in genes that are microglia specific, or highly expressed in microglia, that are associated with increased risk of LOAD, suggesting altered regulation of microglial functions to be involved in the pathogenesis of LOAD. Using microglia isolated from the 5xFAD mouse model of AD, we identified by bulk and single cell RNA-seq that plaque phagocytosing (X04+) and non-plaque phagocytosing (X04-) microglia are distinct microglial populations separable by their transcriptomic signature. Our study suggests that X04+ microglia are a homogenous population of microglia with a distinct gene expression profile associated with amyloid uptake. In contrary, X04- microglia are associated with an age-related transcriptomic profile and may be involved in the over-pruning of synapses in 5xFAD mice. We also demonstrated that microglia can undergo transcriptomic changes upon exposure to different environmental cues.
Although therapeutic approaches that target different pathological features of AD have been evaluated, clinical translation of therapeutics has been very unsuccessful. This could be in part due to potential therapeutics targeting a single disease pathology. To identify new therapeutic candidates for the treatment of AD, this study also explored the use of metal-based compounds as a multi-targeting therapeutic strategy. Five novel metal-based compounds were screened to identify leading compounds that confer neuroprotective, metal-regulating and inflammation-modulating effects in a generic model of neuroinflammation. LM47 was identified as the only leading compound that exerted inflammatory-modulating activity through copper-associated action. Further testing of LM47 showed that the compound was well-tolerated in vivo. However, data by pharmacokinetic study and ICP-MS suggest that the copper free ligand LM46, and not LM47, acts as the active compound in vivo. Treatment of 5xFAD mice with LM46 increased the proportion of X04+ microglia in brain. However, Both LM46 and LM47 treatment of 5xFAD mice induced increased brain Aβ plaque load in the animals. Taken together, findings from our study suggest that improved targeting of specific microglia sub-population in AD could confer therapeutic outcomes.
Subjects/Keywords: Alzheimer's disease; copper; metal homeostasis; neuroinflammtion; microglia
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APA (6th Edition):
Choo, X. Y. (2018). Development of novel therapeutic approaches for treatment of Alzheimer's disease. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/216470
Chicago Manual of Style (16th Edition):
Choo, Xin Yi. “Development of novel therapeutic approaches for treatment of Alzheimer's disease.” 2018. Doctoral Dissertation, University of Melbourne. Accessed January 21, 2021.
http://hdl.handle.net/11343/216470.
MLA Handbook (7th Edition):
Choo, Xin Yi. “Development of novel therapeutic approaches for treatment of Alzheimer's disease.” 2018. Web. 21 Jan 2021.
Vancouver:
Choo XY. Development of novel therapeutic approaches for treatment of Alzheimer's disease. [Internet] [Doctoral dissertation]. University of Melbourne; 2018. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/11343/216470.
Council of Science Editors:
Choo XY. Development of novel therapeutic approaches for treatment of Alzheimer's disease. [Doctoral Dissertation]. University of Melbourne; 2018. Available from: http://hdl.handle.net/11343/216470
Texas A&M University
4.
Aksoy, Emre.
Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity.
Degree: PhD, Molecular and Environmental Plant Sciences, 2014, Texas A&M University
URL: http://hdl.handle.net/1969.1/152841
► The expression of genes that control iron (Fe) uptake and distribution (i.e., Fe utilization- related genes) is under a strict regulation. Fe deficiency strongly induces…
(more)
▼ The expression of genes that control iron (Fe) uptake and distribution (i.e., Fe utilization-
related genes) is under a strict regulation. Fe deficiency strongly induces Fe utilization-
related gene expression; however, little is known about the mechanisms that regulate this
response in plants. In this dissertation, a RNA metabolism factor, RNA POLYMERASE II
CTD-PHOSPHATASE-LIKE1 (CPL1) was shown to localize to the root stele, and to be
involved in the regulation of Fe deficiency responses in Arabidopsis thaliana. An analysis
of multiple cpl1 alleles established that cpl1 mutations enhanced transcriptional responses
of Fe utilization-related genes, e.g. IRON-REGULATED TRANSPORTER1 (IRT1), to low
Fe availability. In addition to the lower Fe content in the roots, but higher Fe content in
the shoots of cpl1-2 plants, the root growth of cpl1-2 showed improved tolerance to Fe
deficiency. Genetic data indicated that cpl1-2 likely activates Fe deficiency responses
upstream of both FE–DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT)-
dependent and -independent signaling pathways. Interestingly, various osmotic
stress/ABA-inducible genes were up-regulated in cpl1-2, and the expression of some
ABA-inducible genes was controlled by Fe availability.
Unlike Fe, accumulation of the heavy-
metal cadmium (Cd) in plants is toxic and it is
absorbed by the roots due to the low selectivity of
metal transporters such as AtIRT1. In
this dissertation, CPL1 was also shown to regulate the transcriptional responses to Cd
toxicity. cpl1-2 showed higher tolerance to the Cd toxicity by enhancing the root-to-shoot
translocation of Cd by an unknown mechanism. A knowledge-based screening resulted
in identification of a putative
metal transporter, OLIGOPEPTIDE TRANSPORTER (OPT),
which was highly induced in cpl1-2 upon exposure to Cd. OPT was localized to the
plastids, indicating a role of plastids in Cd transport and accumulation. The root growth
of opt mutants showed higher tolerance to the Cd toxicity, and the mutants accumulated
less Cd, Fe and Zn, indicating the involvement of OPT in the transport of these metals.
This presented dissertation suggests that 1) CPL1 functions as a negative regulator of the
Fe deficiency signaling at the crosstalk with a branch of the osmotic stress/ABA signaling
pathway, and 2) CPL1 regulates the Cd distribution in plants by repressing the expression
of OPT.
Advisors/Committee Members: Koiwa, Hisashi (advisor), Zhu-Salzman, Keyan (committee member), Pepper, Alan E (committee member), Hirschi, Kendal D (committee member), Finlayson, Scott A (committee member).
Subjects/Keywords: Arabidopsis; cadmium; iron; metal; CTD; RNA metabolism; microarray; homeostasis
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APA ·
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Manager
APA (6th Edition):
Aksoy, E. (2014). Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/152841
Chicago Manual of Style (16th Edition):
Aksoy, Emre. “Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity.” 2014. Doctoral Dissertation, Texas A&M University. Accessed January 21, 2021.
http://hdl.handle.net/1969.1/152841.
MLA Handbook (7th Edition):
Aksoy, Emre. “Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity.” 2014. Web. 21 Jan 2021.
Vancouver:
Aksoy E. Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity. [Internet] [Doctoral dissertation]. Texas A&M University; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1969.1/152841.
Council of Science Editors:
Aksoy E. Arabidopsis Thaliana CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-Like1 (CPL1) Mediates Responses to Iron Deficiency and Cadmium Toxicity. [Doctoral Dissertation]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/152841
University of Miami
5.
Ebanks, Sue C.
The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development.
Degree: PhD, Marine Biology and Fisheries (Marine), 2010, University of Miami
URL: https://scholarlyrepository.miami.edu/oa_dissertations/658
► Freshwater organisms are known to maintain hyperosmotic internal conditions despite outward diffusive loss of ions. The freshwater common pond snail Lymnaea stagnalis faces this…
(more)
▼ Freshwater organisms are known to maintain hyperosmotic internal conditions despite outward diffusive loss of ions. The freshwater common pond snail
Lymnaea stagnalis faces this challenge while additionally attaining the necessary ions for calcification. These are the first documented assessments of the time and mode of recovery for ions lost due to full-body withdrawal in adults of this species. Additionally, this document reports on the physiological and developmental onset of embryonic calcification and the commencement of active acquisition of shell-forming ions from the surrounding environment. The effect of water chemistry and lead (Pb) exposure on embryonic growth, development, and calcium (Ca
2+) acquisition was also tested. Pharmacological and water chemistry manipulations were used to determine mechanisms for embryonic Ca
2+ and HCO
3-/CO
32- acquisition and the sensitivity of those pathways. Lastly,
L. stagnalis, was shown to have a lowest effective concentration of -1 using net Ca
2+ uptake, growth, and developmental endpoints in laboratory and natural waters. This is the lowest effective concentration observed for any organism to date. One of the most insightful findings reported here is the interconnectedness of the pathways for acquisition of Na
+ and Ca
2+ through endogenous production of H
+ and HCO
3- via carbonic anhydrase-catalyzed hydration of metabolic CO
2. The combination of high demand for Ca
2+ throughout early life stages and periodic acute demands for Na
+ recovery following extracellular fluid loss apparently causes
L. stagnalis to be highly sensitive to changes in water chemistry, including [Pb] in the embryos, and possibly pH. The findings reported here warn of the need to establish freshwater environmental indicators and consider raising awareness of the threat of freshwater acidification, which may be greater than that of ocean acidification.
Advisors/Committee Members: Martin Grosell, Christopher M. Wood, David Letson, Christopher Langdon, Lynne Fieber.
Subjects/Keywords: Homeostasis; Calcium; Water Chemistry; Invertebrate; Metal Toxicology; Freshwater Physiology
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APA (6th Edition):
Ebanks, S. C. (2010). The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/658
Chicago Manual of Style (16th Edition):
Ebanks, Sue C. “The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development.” 2010. Doctoral Dissertation, University of Miami. Accessed January 21, 2021.
https://scholarlyrepository.miami.edu/oa_dissertations/658.
MLA Handbook (7th Edition):
Ebanks, Sue C. “The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development.” 2010. Web. 21 Jan 2021.
Vancouver:
Ebanks SC. The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2021 Jan 21].
Available from: https://scholarlyrepository.miami.edu/oa_dissertations/658.
Council of Science Editors:
Ebanks SC. The Common Pond Snail Lymnaea stagnalis: Extracellular Fluid Recovery in Adults and Calcification and Lead Sensitivity During Embryonic Development. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/658
York University
6.
Chandrapalan, Theanuga.
Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio).
Degree: MSc -MS, Biology, 2019, York University
URL: https://yorkspace.library.yorku.ca/xmlui/handle/10315/36794
► Iron (Fe) is an essential trace metal for development; however, its level in the body must be maintained within physiological range. In the present study,…
(more)
▼ Iron (Fe) is an essential trace
metal for development; however, its level in the body must be maintained within physiological range. In the present study, the effects of dietary Fe on growth, trace
metal homeostasis, and the expression of various
metal transporting genes were investigated during development in zebrafish (Danio rerio). The results demonstrated that growth and whole body Fe content were substantially higher in 14 dpf larvae fed high Fe diets. Interestingly, prolonged exposure to high Fe increased mortality but did not affect the levels of Fe and other trace metals (e.g., Zn2+, Cu2+, Mn2+, Ni2+) in 28 dpf larvae. Molecular analysis revealed that exposure to high dietary Fe induced differential changes in the mRNA expression levels of various
metal transporters (e.g., dmt1, zip8, and zip14). These findings suggested that the maintenance of
metal homeostasis following Fe exposure was likely associated with the dynamic regulation of
metal transporting proteins.
Advisors/Committee Members: Kwong, Raymond (advisor).
Subjects/Keywords: Biology; Iron; Metal homeostasis; Dietary exposure; Development; Zebrafish
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APA (6th Edition):
Chandrapalan, T. (2019). Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio). (Masters Thesis). York University. Retrieved from https://yorkspace.library.yorku.ca/xmlui/handle/10315/36794
Chicago Manual of Style (16th Edition):
Chandrapalan, Theanuga. “Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio).” 2019. Masters Thesis, York University. Accessed January 21, 2021.
https://yorkspace.library.yorku.ca/xmlui/handle/10315/36794.
MLA Handbook (7th Edition):
Chandrapalan, Theanuga. “Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio).” 2019. Web. 21 Jan 2021.
Vancouver:
Chandrapalan T. Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio). [Internet] [Masters thesis]. York University; 2019. [cited 2021 Jan 21].
Available from: https://yorkspace.library.yorku.ca/xmlui/handle/10315/36794.
Council of Science Editors:
Chandrapalan T. Influence of Dietary Iron Exposure on the Physiological Regulation of Iron and other Trace Metals During Development in Zebrafish (Danio Rerio). [Masters Thesis]. York University; 2019. Available from: https://yorkspace.library.yorku.ca/xmlui/handle/10315/36794
University of Toronto
7.
Lacasse, Michael Joseph.
Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation.
Degree: PhD, 2019, University of Toronto
URL: http://hdl.handle.net/1807/102758
► [NiFe]-hydrogenases catalyze the reversible oxidation of hydrogen gas at a bimetallic active site and are important enzymes in bacteria and archaea for anaerobic growth and…
(more)
▼ [NiFe]-hydrogenases catalyze the reversible oxidation of hydrogen gas at a bimetallic active site and are important enzymes in bacteria and archaea for anaerobic growth and pathogenesis. The maturation of [NiFe]-hydrogenase requires at least seven dedicated accessory proteins to assemble and insert the components of the NiFe(CN)2CO catalytic site. The penultimate maturation step is the delivery of nickel to a primed hydrogenase precursor protein, a process that is accomplished by the metallochaperone proteins HypA, HypB, and SlyD. This delivery process is supported by proteins that import, export, regulate, and store nickel to ensure a sufficient supply while also mitigating the innate toxicity of this transition metal.
In this work, nickel delivery to the [NiFe]-hydrogenase in Escherichia coli was examined using microbiological, biochemical, spectroscopic, and computational methods. The results demonstrate that protein-protein interactions between the metallochaperones afford layers of nickel selectivity. The protein complexes HypA-HypB and SlyD-HypB are modulated by the GTPase cycle of HypB and mediate the selective release of nickel over zinc. In addition, characterization of the metal-binding sites of HypA and HypB revealed different binding modalities, suggesting distinct acquisition and release mechanisms for these metallochaperones. This thesis also describes the development and employment of a high-throughput whole-cell [NiFe]-hydrogenase assay. The assay was used to screen the Keio collection of single gene deletion strains of E. coli and uncovered, for the first time, eutK as a component of the nickel delivery pathway and nickel homeostasis. The assay was also used to determine extracellular nickel concentrations required to bypass the nickel uptake and delivery processes to validate those systems as potential therapeutic targets, setting the stage for the search for small molecules that inhibit the biosynthesis of [NiFe]-hydrogenase. Together, this work gives insight into several aspects of the crucial nickel delivery process that bacteria use to produce [NiFe]-hydrogenase.
2020-11-13 00:00:00
Advisors/Committee Members: Zamble, Deborah B, Chemistry.
Subjects/Keywords: Escherichia coli; Hydrogenase; Metal Homeostasis; Metallochaperones; Nickel; 0487
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APA (6th Edition):
Lacasse, M. J. (2019). Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/102758
Chicago Manual of Style (16th Edition):
Lacasse, Michael Joseph. “Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation.” 2019. Doctoral Dissertation, University of Toronto. Accessed January 21, 2021.
http://hdl.handle.net/1807/102758.
MLA Handbook (7th Edition):
Lacasse, Michael Joseph. “Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation.” 2019. Web. 21 Jan 2021.
Vancouver:
Lacasse MJ. Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation. [Internet] [Doctoral dissertation]. University of Toronto; 2019. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1807/102758.
Council of Science Editors:
Lacasse MJ. Investigation of Escherichia coli [NiFe]-Hydrogenase Maturation. [Doctoral Dissertation]. University of Toronto; 2019. Available from: http://hdl.handle.net/1807/102758
Texas A&M University
8.
McCormick, Sean P.
The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems.
Degree: PhD, Chemistry, 2014, Texas A&M University
URL: http://hdl.handle.net/1969.1/154123
► Eukaryotic cells contain low-molecular-mass metal complexes (LMMMCs), defined as having masses between 200 – 10,000 Da, but these so-called labile or chelatable metal pools are…
(more)
▼ Eukaryotic cells contain low-molecular-mass
metal complexes (LMMMCs), defined as having masses between 200 – 10,000 Da, but these so-called labile or chelatable
metal pools are poorly defined in terms of structures and functions. LMMMCs are thought to participate in
metal-ion regulation, trafficking, storage and/or signaling in cells. These cellular processes are often dysfunctional in
metal-associated diseases. The objective of these studies was to detect and characterize LMMMCs in eukaryotic cells, organelles and tissues. A novel liquid chromatography system in a cold inert-atmosphere glove box was interfaced with an in-line inductively coupled plasma mass spectrometer, and this LC-ICP-MS system was used to detect LMMMCs in yeast cells, mitochondria, and vacuoles as well as in mouse brain and liver cells and mitochondria. In each biological system, this separations technique was applied to detect numerous LMMMCs. The molecular mass and concentration of such species were estimated.
In yeast, the previously reported mismetallation of MnSOD2 was examined in the mutant strain Δmtm1. A combination of SEC and AEX chromatography revealed that the degree of mismetallation of the SOD2 protein, in which Fe replace Mn in the active site, was no greater in Δmtm1 cells than in WT cells. The mitochondria of such mutant cells did exhibit an intense chromatography peak of Mn corresponding to at mass of 2000 – 3000 Da. Mitochondria from WT cells exhibited a similar species, but at much lower intensity. This was the only Mn species present, suggesting that it was the used to metallate apo-SOD2.
Mitochondria isolated from WT yeast cells contained 6 Co, 3 Cu, 2 Mn, 5 Fe and 3 Zn LMMMCs and approximately 6 P- and S- LLM species. Some of the P- and S- LMMCs probably arose from compounds like ATP, ADP, etc. Molecular masses of the LMM Cu peaks were higher (> 5 kDa) than for the LMM complexes of other transition metals. Zinc, Mn, and Fe had multiple species of interest which demonstrate the presence and labiality of the metals in pools.
The same separation system was utilized to examine mice brain LMM extracts were found to contain > 30 LMMMCs. Eleven Co, 2 Cu, 5 Mn, 4 Mo, 3 Fe and 2 Zn LLM complexes were detected. Most Cu and Zn complexes appeared to be protein-bound with masses ranging from 4–20 kDa. In these systems, Co was the only
metal for which the aqueous complex was reproducibly observed.
A second mouse study used the LC-ICP-MS system to examine the forms of iron present in mouse plasma. Chromatograms exhibited ~6 Fe-associated peaks that were assigned to ferritin, transferrin, and hemopexin, respectively; the other 3 peaks could not be assigned. The LC-ICP-MS experiment demonstrates that numerous Fe-containing species coexist with transferrin in healthy WT mouse plasma.
Advisors/Committee Members: Lindahl, Paul A (advisor), Barondeau, David P (committee member), Hilty, Christian (committee member), Pellois, Jean-Philippe (committee member).
Subjects/Keywords: Labile Metal Pools; Metal Pools; LC-ICP-MS; Metal Speciation; Yeast; Mice Brain; mtm1p; MnSOD; metal trafficking; metal homeostasis; Bioanalytical; Manganese Pool; Low Molecular Mass Metal Complexes; LMM; LMMMCs
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APA (6th Edition):
McCormick, S. P. (2014). The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/154123
Chicago Manual of Style (16th Edition):
McCormick, Sean P. “The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems.” 2014. Doctoral Dissertation, Texas A&M University. Accessed January 21, 2021.
http://hdl.handle.net/1969.1/154123.
MLA Handbook (7th Edition):
McCormick, Sean P. “The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems.” 2014. Web. 21 Jan 2021.
Vancouver:
McCormick SP. The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems. [Internet] [Doctoral dissertation]. Texas A&M University; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1969.1/154123.
Council of Science Editors:
McCormick SP. The Application of LC-ICP-MS to Study Metal Ion Homeostasis in Biological Systems. [Doctoral Dissertation]. Texas A&M University; 2014. Available from: http://hdl.handle.net/1969.1/154123
9.
Avalos, Ana M.
HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana.
Degree: MS, 2004, Worcester Polytechnic Institute
URL: etd-0429104-112415
;
https://digitalcommons.wpi.edu/etd-theses/492
► Metal homeostasis in plants is regulated by diverse mechanisms that act together to maintain optimal metal ion concentrations inside the cell. P1B-ATPases are heavy metal…
(more)
▼ Metal homeostasis in plants is regulated by diverse mechanisms that act together to maintain optimal
metal ion concentrations inside the cell. P1B-ATPases are heavy
metal transport ATPases that are likely to be related to these processes. The sequencing of the genome of Arabidopsis thaliana revealed the presence of eight putative P1B-ATPases, HMA1-8. The main goal in this work is to characterize of the role of P1B-ATPases in plant
metal homeostasis. Toward this goal, the P1B-ATPases HMA1 and HMA6 from Arabidopsis thaliana were cloned from leaves and sequenced. Results from RT-PCR experiments show ubiquitous expression in planta of this two ATPases, except for HMA1 that does not express in roots. Upon Cu2+ exposure during growth, expression of HMA6 increases in seedlings. HMA1 expression increases when seedlings are grown in high Cu2+ and Co2+ media, and decreases when grown in high concentrations of Zn2+ and Ni2+. hma1-1 plants have smaller size and less chlorophyll content than WT plants. Growth is affected in hma1-1 seedlings when grown in Zn2+, Mn2+, Fe2+, Co2+ and Cu2+ deficient media, or when these metals are in excess. Moreover, hma1-1 plants show an increase in Zn2+, Mn2+ and Fe2+ content in whole plants compared to WT plants. Mutant plants also show increased levels of HMA3 and HMA4 transcripts (Zn2+/Cd2+/Pb2+ P1B-ATPases), upregulation of metallothioneins 1a and 2b, downregulation of metallothionein 1c, and a decrease in the phytochellatin synthases 1 and 2 transcripts, compared to WT plants. Homozygous for mutation in HMA6 seems to be lethal, given that none was recovered after screening. These results indicate HMA1 and HMA6 as essential components of plant
metal homeostasis in Arabidopsis thaliana.
Advisors/Committee Members: José M. Argüello, Advisor, ;.
Subjects/Keywords: plant metal homeostasis; P1B ATPases; Metal ions; Homeostasis; Carrier proteins; Arabidopsis thaliana
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APA (6th Edition):
Avalos, A. M. (2004). HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana. (Thesis). Worcester Polytechnic Institute. Retrieved from etd-0429104-112415 ; https://digitalcommons.wpi.edu/etd-theses/492
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Avalos, Ana M. “HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana.” 2004. Thesis, Worcester Polytechnic Institute. Accessed January 21, 2021.
etd-0429104-112415 ; https://digitalcommons.wpi.edu/etd-theses/492.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Avalos, Ana M. “HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana.” 2004. Web. 21 Jan 2021.
Vancouver:
Avalos AM. HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana. [Internet] [Thesis]. Worcester Polytechnic Institute; 2004. [cited 2021 Jan 21].
Available from: etd-0429104-112415 ; https://digitalcommons.wpi.edu/etd-theses/492.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Avalos AM. HMA1 and HMA6 are essential components of metal homeostasis in Arabidopsis thaliana. [Thesis]. Worcester Polytechnic Institute; 2004. Available from: etd-0429104-112415 ; https://digitalcommons.wpi.edu/etd-theses/492
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
NSYSU
10.
Wu, Tsung-meng.
Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity.
Degree: PhD, Marine Biology, 2009, NSYSU
URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1228109-120140
► This is the first research by using suppression subtractive hybridization (SSH) to analysis the gene expression in marine macroalga Ulva fasciata Delile against excess copper…
(more)
▼ This is the first research by using suppression subtractive hybridization (SSH) to analysis the gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity, and it gives us a comprehensive understanding of the tolerant mechanism while macroalgae face to the excess copper. Suppression subtractive hybridization was used to identify genes differentially expressed following exposure to 50 μM CuSO4 for 6- 12h in a marine macroalga Ulva fasciata Delile. In this work, 69 genes were identified, of which 55 were up-regulated and 14 were down-regulated. According to the database of Gene Ontology (GO), these genes were classified into 10 categories as follows: 1. Transcription; 2. Translation, ribosomal structure and biogenesis; 3. Posttranslational modification, protein turnover, chaperones; 4. Photosynthesis; 5. Cell redox
homeostasis; 6. Stress; 7. Metabolism; 8. Energy production and conversion; 9. Transport; 10. Function unknown. According to the results, we suggest that the responses of U. fasciata against excess copper toxicity are mainly through increase of the energy production for providing sufficient energy to many metabolic pathways, and control of the Fe
homeostasis and redox form of thiol groups for maintaining the cellular redox
homeostasis, moreover, expression of photosynthetic genes for letting the photosynthesis work. In addition, to scavenge the ROS is by expression of stress-related genes, meanwhile, the proteins, DNA and lipids damaged by ROS (reactive oxygen species) and copper are repaired by expression of the other categorical genes. Over and above, the genes expressing in the metabolism category might maintain the amino acids
homeostasis and increase the purine content, and subsequently increase the tolerant capacity of U. fasciata against excess copper toxicity. In addition, the concentrations of antioxidants and the activities and gene expression of antioxidant enzymes were determined in Ulva fasciata Delile by a 4-day exposure to 0, 5, 10, 20 and 50 μM CuSO4. These results demonstrate that the maintenance of antioxidant
homeostasis and the induction of activities of antioxidant enzymes via enhanced gene expression are used by U. fasciata to cope with the Cu-induced oxidative stress, but the defense capacity cannot sufficiently alleviate oxidative damage occurring under the condition of higher Cu concentrations. Moreover, according to the results from the expression of genes involved in the control of redox
homeostasis and antioxidant defense was studied in macroalga Ulva fasciata Delile in response to CuSO4 (5 and 50 μM) and ROS (H2O2 and O2Ë-), we suggest that ROS involved in up-regulation of antioxidant defense-related genes and the expression of genes of antioxidant defense enzymes and UfMsrA (methionine sulfoxide reductase A) are associated with long-term adaptation of U. fasciata to Cu excess and transcription of redox- related genes and UfGr (glutathione reductase) is up-regulated for short-term acclimation. Promoters play a key role in regulating gene…
Advisors/Committee Members: Hao-Jen Huang (chair), Zin-Huang Liu (chair), Kuo-Chen Yeh (chair), Ming-Tsair Chan (chair), Yi-Ting Hsu (chair), Tse-Min Lee (committee member), Ching-Huei Kao (chair).
Subjects/Keywords: Ulva fasciata; copper; heavy metal; oxidative stress; redox homeostasis; gene expression; suppression subtractive hybridization
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APA (6th Edition):
Wu, T. (2009). Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1228109-120140
Chicago Manual of Style (16th Edition):
Wu, Tsung-meng. “Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity.” 2009. Doctoral Dissertation, NSYSU. Accessed January 21, 2021.
http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1228109-120140.
MLA Handbook (7th Edition):
Wu, Tsung-meng. “Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity.” 2009. Web. 21 Jan 2021.
Vancouver:
Wu T. Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity. [Internet] [Doctoral dissertation]. NSYSU; 2009. [cited 2021 Jan 21].
Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1228109-120140.
Council of Science Editors:
Wu T. Gene expression in marine macroalga Ulva fasciata Delile against excess copper toxicity. [Doctoral Dissertation]. NSYSU; 2009. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1228109-120140
University of Michigan
11.
Tebo, Alison G.
De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis.
Degree: PhD, Chemical Biology, 2015, University of Michigan
URL: http://hdl.handle.net/2027.42/113513
► Protein design is a powerful way to interrogate the basic requirements for function of metal sites by systematically incorporating elements important for function. Single-stranded three-helix…
(more)
▼ Protein design is a powerful way to interrogate the basic requirements for function of
metal sites by systematically incorporating elements important for function. Single-stranded three-helix bundles with either thiolate-rich sites for spectroscopic characterization and electron transfer, or histidine-rich sites for redox catalysis are described.
Using a previous design, two constructs were designed to incorporate a fourth cysteine residue to investigate thiolate-rich sites involved in
metal ion
homeostasis and electron transfer. Rational re-design replaced a putative coordinating histidine with a cysteine. A second construct embedded a CXXC binding motif into the helical scaffold. These two constructs show different UV-visisble, 113Cd NMR, and 111mCd PAC, which indicate that they form different proportions of CdS3O and CdS4. The spectroscopy of these sites sheds light on how Cd(II) bindis to CadC and suggests a dynamic site in fast exchange with the solvent.
Previous attempts at the design of a rubredoxin site have focused on reproducing the peptide fold around or using flexible loop regions to define the site in addition to canonical CXXC motifs. However, the use of CXXC motifs embedded in an α-helical scaffold produces a rubredoxin site that reproduces the Mössbauer, MCD, and EPR of rubredoxin without the use of loop regions. This successful design is the largest deviation from consensus rubredoxin and zinc finger folds reported.
Electron transfer rates through a de novo designed scaffold were studied by the design and synthesis of a ruthenium trisbipyridine derivative appended to an exterior cysteine residues. A redox-active tyrosine in the 70th position is implicated as a relay amino acid from the iron center and absence of the tyrosine decreases the rate of electron transfer from the
metal site. This is the first photo-generated tyrosine radical in a designed protein.
A construct, which was previously reported for CO2 hydration, is substituted with copper and its spectroscopic and nitrite reductase activity are studied. This is the first demonstration of nitrite reductase activity in a single-stranded designed peptide.
This thesis provides insight into designed proteins and their applications and lays the groundwork for further studies to progress towards a unified multifunctional redox protein.
Advisors/Committee Members: Aukauloo, Ally (committee member), Pecoraro, Vincent L. (committee member), Fierke, Carol A. (committee member), Lehnert, Nicolai (committee member), Ballou, David P. (committee member).
Subjects/Keywords: metal homeostasis; electron transfer protein; laser flash photolysis; tyrosine radical; nitrite reductase; Chemistry; Science
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APA ·
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CSE |
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Manager
APA (6th Edition):
Tebo, A. G. (2015). De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/113513
Chicago Manual of Style (16th Edition):
Tebo, Alison G. “De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis.” 2015. Doctoral Dissertation, University of Michigan. Accessed January 21, 2021.
http://hdl.handle.net/2027.42/113513.
MLA Handbook (7th Edition):
Tebo, Alison G. “De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis.” 2015. Web. 21 Jan 2021.
Vancouver:
Tebo AG. De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis. [Internet] [Doctoral dissertation]. University of Michigan; 2015. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/2027.42/113513.
Council of Science Editors:
Tebo AG. De Novo Designed Metallopeptides to Investigate Metal Ion Homeostasis, Electron Transfer, and Redox Catalysis. [Doctoral Dissertation]. University of Michigan; 2015. Available from: http://hdl.handle.net/2027.42/113513
12.
Han, Thi-Hong-Liên.
Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress.
Degree: Docteur es, Chimie. Physico-Chimie, 2016, Sorbonne Paris Cité
URL: http://www.theses.fr/2016USPCC288
► La frataxine est une protéine mitochondriale bien conservée de la bactérie à l’homme. La déficience de la frataxine chez l’homme entraine une maladie neurodégénérative grave,…
(more)
▼ La frataxine est une protéine mitochondriale bien conservée de la bactérie à l’homme. La déficience de la frataxine chez l’homme entraine une maladie neurodégénérative grave, appelée Ataxie de Friedreich. Cette protéine a été découverte dans les années 90s et depuis sa fonction physiologique exacte n’est toujours pas connue. La frataxine joue un rôle important dans la biosynthèse des centres Fe-S dans l’homéostasie du fer et/ou dans la protection contre le stress oxydant. Dans cette thèse, nous nous intéressons aux interactions entre la protéine et d’autres molécules, comme certains métaux mitochondriaux ou protéines pour mieux comprendre la fonction de la frataxine dans la cellule. Lors de ce travail, la frataxine de levure (Yfh1) a été synthétisée par la technique de l’ADN recombinant, puis purifiée pour les études physico-chimiques. La flavohémoglobine (Yhb1)qui joue le rôle important dans la détoxification de NO (un agent du stress oxydatif et nitrosatif) a été aussi exprimée et purifiée selon le même principe. Ensuite, nous avons étudié la thermodynamique et la cinétique de la complexation de Yfh1 par les métaux mitochondriaux comme Fe, Cu, Mn, Zn, ainsi qu’avec les protéines impliquées dans le système antioxydant comme les superoxydes dismutases, CuZnSOD et MnSOD, et la flavohémoglobine. Ces résultats montrent tout d’abord que Yfh1 interagit avec tous les métaux mitochondriaux,néanmoins elle présente une meilleure affinité pour le cuivre et le manganèse. Par la suite, nous mettons en évidence le rôle remarquable de la frataxine dans le système antioxydant. Nous attribuons ainsi à la frataxine un rôle de protéine multifonctionnelle : « régulateur » dans le métabolisme des métaux.
The frataxin is a mitochondrial protein which is highly conserved during the evolution. The deficiency of frataxinin human induces a neurodegenerative disease: Friedreich’s ataxia. This protein was discovered in the nineties.However, its functions are always opened questions. It has been shown that frataxin participates in the assemblyof Fe-S cluster, as well as the iron homeostasis and cellular antioxidant system. The interactions between frataxinand others molecules, such as metals or proteins, are necessary for a better understanding of protein’s functions.In this work, we synthesized a yeast frataxin homologue (Yfh1) by DNA recombinant technique, and thenpurified it for cell free studies. Yeast flavohemoglobin (Yhb1), which is responsible for the detoxification of NO(an oxidative and nitrosative stress agent), was also isolated. We started by determining the thermodynamics andkinetics of the physiological interaction between Yfh1 and mitochondrial metals, such as Fe, Cu, Mn and Zn, aswell as the interaction with the gatekeepers in the anti-oxidative stress such as superoxide dismutases, CuZnSOD& MnSOD, and Yhb1. We underline here, in the first part the unspecific interaction of Yfh1 with mitochondrialmetals, and more especially the higher affinity of Yfh1 for copper and manganese than for iron. We also confirmthe remarkable…
Advisors/Committee Members: Ha-Duong, Nguyêt-Thanh (thesis director), El Hage Chahine, Jean-Michel (thesis director).
Subjects/Keywords: Homéostasie métallique; Métaux mitochondriaux; Relaxation chimique; Metal homeostasis; Mitochondrial metals; Relaxation chemistry
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APA ·
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APA (6th Edition):
Han, T. (2016). Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2016USPCC288
Chicago Manual of Style (16th Edition):
Han, Thi-Hong-Liên. “Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress.” 2016. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 21, 2021.
http://www.theses.fr/2016USPCC288.
MLA Handbook (7th Edition):
Han, Thi-Hong-Liên. “Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress.” 2016. Web. 21 Jan 2021.
Vancouver:
Han T. Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2016. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2016USPCC288.
Council of Science Editors:
Han T. Etudes de la fonction de la frataxine : relations avec l'homéostasie métallique et le stress oxydant. : Functional studies of Frataxin : relations with metal homeostasis and oxidatives stress. [Doctoral Dissertation]. Sorbonne Paris Cité; 2016. Available from: http://www.theses.fr/2016USPCC288
University of Minnesota
13.
Tian, Hui.
Phloem functions revealed by the nakr1-1 mutant.
Degree: Plant Biological Sciences, 2011, University of Minnesota
URL: http://purl.umn.edu/101986
► Na+ is a non- essential element for plant growth. Na+ accumulation within plants, especially the shoot tissue causes osmotic stress and Na+-specific toxicity that threatens…
(more)
▼ Na+ is a non- essential element for plant growth. Na+ accumulation within
plants, especially the shoot tissue causes osmotic stress and Na+-specific
toxicity that threatens plant survival and reduces crop yield. The control of Na+
accumulation in the shoot is mainly at the root level, by regulating net Na+
uptake into roots and Na+ transport from root to the shoot. My thesis work is
mainly on the characterization of a fast neutron mutagenized Arabidopsis
mutant, nakr1-1, that accumulates Na+ and K+ in the shoot tissue and has
pleiotrophic developmental phenotypes (including short roots, late flowering and
loss of apical dominance). Using traditional mapping together with DNA- chip
based mapping, a 7-bp deletion was identified that caused loss- of- function
mutation of a gene encoding a putative heavy-metal-binding protein. The metalbinding
feature of the protein was confirmed by elemental analysis of maltose
binding protein (MBP)- tagged NaKR1 expressed and purified from Escherichia
coli. AtNaKR1 was specifically expressed in the phloem companion cells.
NaKR1 protein was phloem mobile and unloaded at the phloem terminal into
the proximal root meristem region. nakr1-1 mutation caused severe phloem
function defects as demonstrated by less efficient 14C- sucrose loading and
starch accumulation in rosette leaves. Phloem function defects were also
responsible for the Na+/K+ accumulation in the shoot tissue based on the
reciprocal grafting results together with ICP- MS analyses. Moreover elemental
analysis of xylem sap indicated Na+ and K+ accumulation phenotypes were not
caused by increased root- to- shoot transport of Na+ and K+. nakr1-1 mutation affects root meristem maintenance after germination as revealed by study of
root meristem size, cell pattern and starch accumulation in root columella cells
and quiescent center activity. My work provided evidence that phloem
recirculation plays more important roles than had been suggested by previous
literature in controlling shoot Na+ accumulation. Understanding how Na+ and K+
redistribution is regulated might have potential application in improving salinity
tolerance of crop plants and the improvement of seed quality.
Subjects/Keywords: Companion cell; Heavy metal binding protein; Na+/ K+ homeostasis; Mobile; Phloem specific; Root Meristem
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tian, H. (2011). Phloem functions revealed by the nakr1-1 mutant. (Thesis). University of Minnesota. Retrieved from http://purl.umn.edu/101986
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tian, Hui. “Phloem functions revealed by the nakr1-1 mutant.” 2011. Thesis, University of Minnesota. Accessed January 21, 2021.
http://purl.umn.edu/101986.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tian, Hui. “Phloem functions revealed by the nakr1-1 mutant.” 2011. Web. 21 Jan 2021.
Vancouver:
Tian H. Phloem functions revealed by the nakr1-1 mutant. [Internet] [Thesis]. University of Minnesota; 2011. [cited 2021 Jan 21].
Available from: http://purl.umn.edu/101986.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tian H. Phloem functions revealed by the nakr1-1 mutant. [Thesis]. University of Minnesota; 2011. Available from: http://purl.umn.edu/101986
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Duke University
14.
Hunsaker, Elizabeth.
Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
.
Degree: 2019, Duke University
URL: http://hdl.handle.net/10161/20106
► Maintenance of metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more metal cofactors.…
(more)
▼ Maintenance of
metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more
metal cofactors. We show that the opportunistic fungal pathogen Candida albicans becomes sensitized to both Cu limitation and Cu elevation during exposure in liquid culture to the antifungal drug fluconazole, a widely prescribed antifungal agent. Cu supplementation reduces tolerance of C. albicans to fluconazole in a way that does not require formation of a Cu–fluconazole complex. Rather, our data point to a less obvious relationship between drug stress and Cu availability that gives rise to
metal-mediated outcomes of drug treatment. qRT-PCR, EPR, fluorescence, and ICP-MS studies demonstrate that C. albicans extensively remodels its
metal homeostasis networks to respond to treatment with fluconazole. These adaptation strategies include increased Cu import and storage, increased retention of Fe, Mn, and Zn, altered utilization of Cu- and Mn-dependent enzymes, mobilization of intracellular Fe stores, and increased production of the heme prosthetic group utilized by the enzyme target of fluconazole. Furthermore, RNA-seq analysis reveals that co-treatment with fluconazole and Cu gives rise to unique patterns of gene expression that illustrate the profound impacts of small fluctuations in Cu availability on the transcriptomic response to fluconazole stress. Finally, we show that fluconazole causes substantial changes to the metalloproteome of C. albicans, most notably to the levels of Cu proteins. The findings offer a new perspective for thinking about fungal response to drug stress that pushes cells out of their
metal homeostatic zones, leading them to enact
metal-associated adaptation mechanisms to restore
homeostasis to survive.
Advisors/Committee Members: Franz, Katherine J (advisor).
Subjects/Keywords: Chemistry;
Inorganic chemistry;
Microbiology;
Candida albicans;
Copper;
Drug stress;
Fungal infection;
Metal homeostasis
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APA (6th Edition):
Hunsaker, E. (2019). Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/20106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hunsaker, Elizabeth. “Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
.” 2019. Thesis, Duke University. Accessed January 21, 2021.
http://hdl.handle.net/10161/20106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hunsaker, Elizabeth. “Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
.” 2019. Web. 21 Jan 2021.
Vancouver:
Hunsaker E. Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
. [Internet] [Thesis]. Duke University; 2019. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10161/20106.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hunsaker E. Insight into the Role of Metal Homeostasis in Fungal Adaptation to Drug Stress
. [Thesis]. Duke University; 2019. Available from: http://hdl.handle.net/10161/20106
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
15.
Carballido Lopez, Ana Yaiza.
Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2018, Université de Strasbourg
URL: http://www.theses.fr/2018STRAJ008
► Les métaux biologiques jouent un rôle clé en tant que cofacteurs, contribuant à la structuration des macromolécules et catalysant les réactions biochimiques dans les cellules.…
(more)
▼ Les métaux biologiques jouent un rôle clé en tant que cofacteurs, contribuant à la structuration des macromolécules et catalysant les réactions biochimiques dans les cellules. Ils sont nécessaires pour une croissance bactérienne optimale mais deviennent toxiques lorsqu'ils sont présents en excès. Par conséquent, l'homéostasie de ces métaux doit être finement régulée, et tout déséquilibre dans leur concentration pourrait affecter la viabilité cellulaire. Lors de cette thèse nous avons investigué les mécanismes moléculaires impliqués dans l'homéostasie du Fe chez Pseudomonas aeruginosa, en étudiant les deux principaux sidérophores produits par cette bactérie, pyoverdine (PVD) et pyochéline (PCH). Avec notre approche, nous avons identifié des nouveaux mécanismes de régulation des voies d’acquisition du fer par PVD et PCH. Nous avons également étudié comment d'autres métaux biologiques peuvent interférer avec ces voies, et le Co a montré une forte propension à pirater et à polluer la voie PCH.
Biological metals (Fe, Zn, Co, Ni, Mn, Cu) play a key role by acting as co-factors, contributing to macromolecule structuration, and catalyzing biochemical reactions into the cells. They are required for optimal bacterial growth but also become toxic when present in excess. Consequently, the homeostasis of these metals has to be finely regulated, and any disequilibrium in their concentration into bacteria could affect cell viability. We have further investigated the molecular mechanisms implicated in Fe homeostasis in Pseudomonas aeruginosa involving the two major siderophores produced by this bacterium, pyoverdine (PVD) and pyochelin (PCH). With our approach we identified new regulation mechanisms of both PVD and PCH pathways. In parallel, we have also investigated how other biological metals than Fe can interfere with these iron uptake pathways. Our data showed a strong propensity of Co to pirate and pollute the PCH iron uptake pathway.
Advisors/Committee Members: Schalk, Isabelle (thesis director).
Subjects/Keywords: Métal; Homéostasie; Cobalt; Fer; Pyochéline; Pyoverdine; P. aeruginosa; Régulation; Metal; Homeostasis; Cobalt; Iron; Pyochelin; Pyoverdine; P. aeruginosa; Regulation; 579.3; 572.4
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APA (6th Edition):
Carballido Lopez, A. Y. (2018). Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2018STRAJ008
Chicago Manual of Style (16th Edition):
Carballido Lopez, Ana Yaiza. “Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa.” 2018. Doctoral Dissertation, Université de Strasbourg. Accessed January 21, 2021.
http://www.theses.fr/2018STRAJ008.
MLA Handbook (7th Edition):
Carballido Lopez, Ana Yaiza. “Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa.” 2018. Web. 21 Jan 2021.
Vancouver:
Carballido Lopez AY. Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2018. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2018STRAJ008.
Council of Science Editors:
Carballido Lopez AY. Rôle des voies d'import du fer impliquant des sidérophores dans l'homéostasie de métaux biologiques autres que le fer chez Pseudomonas aeruginosa : Role of pyoverdine and pyochelin siderophores in the homeostasis of biological metals different than iron in Pseudomonas aeruginosa. [Doctoral Dissertation]. Université de Strasbourg; 2018. Available from: http://www.theses.fr/2018STRAJ008
McMaster University
16.
Moldovan, Nataliya.
MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS.
Degree: MSc, 2012, McMaster University
URL: http://hdl.handle.net/11375/12372
► Transition metals, such as iron, manganese, and copper are essential in the development and function of biological systems. However, disrupted levels of transition metals…
(more)
▼ Transition metals, such as iron, manganese, and copper are essential in the development and function of biological systems. However, disrupted levels of transition metals are highly cytotoxic, and metal homeostasis is strictly maintained in cells under normal conditions. The neuropathology of several brain disorders, such as Alzheimer’s disease and Parkinson’s disease has been linked to altered metal levels. This work focused on the measurement of iron, manganese, and copper, with the aim of better elucidating their role in brain disease. Two experiments were carried out in C57Bl/6 mice looking at metal homeostasis: 1. following manganese injections typically administered in manganese-enhanced MRI animal studies, and 2. following copper deficiency in a cuprizone model of demyelination. Metal measurements were made in the brain and visceral organs using X-ray fluorescence to measure iron and copper concentrations, and neutron activation analysis to measure manganese concentrations. In the MEMRI study in this work, in addition to the expected manganese concentration increases in brain regions, a statistically significant decrease in iron concentration in the thalamus was found. This change in iron levels in the thalamus following manganese injections should serve as a caution that care should be taken when interpreting signal changes in brain regions. The cuprizone study in this thesis confirmed that copper levels are reduced following cuprizone administration. Surprisingly, manganese concentrations were significantly higher in several brain regions that have demyelination in this model, but not iron or copper. The mechanism of cuprizone toxicity was related to manganese neurotoxicity that may contribute to demyelination.
Master of Science (MSc)
Advisors/Committee Members: Bock, Nicholas, Farquharson, Michael, Valliant, John, Medical Physics.
Subjects/Keywords: transition metal homeostasis; cuprizone; manganese enhanced MRI; manganese overexposure; demyelination; x-ray fluorescence; neutron activation analysis; Medical Biophysics; Medical Biophysics
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APA (6th Edition):
Moldovan, N. (2012). MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/12372
Chicago Manual of Style (16th Edition):
Moldovan, Nataliya. “MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS.” 2012. Masters Thesis, McMaster University. Accessed January 21, 2021.
http://hdl.handle.net/11375/12372.
MLA Handbook (7th Edition):
Moldovan, Nataliya. “MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS.” 2012. Web. 21 Jan 2021.
Vancouver:
Moldovan N. MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS. [Internet] [Masters thesis]. McMaster University; 2012. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/11375/12372.
Council of Science Editors:
Moldovan N. MEASUREMENT OF TRANSITION METALS IN THE RODENT BRAIN USING X-RAY FLUORESCENCE AND NEUTRON ACTIVATION ANALYSIS. [Masters Thesis]. McMaster University; 2012. Available from: http://hdl.handle.net/11375/12372
University of Western Ontario
17.
Pinter, Tyler B. J.
Reactions between Zinc Metallothionein and Carbonic Anhydrase.
Degree: 2015, University of Western Ontario
URL: https://ir.lib.uwo.ca/etd/3212
► More than 25% of proteins require metal ion cofactors for structure or function. The interactions between metalloproteins have largely been overlooked, though these interactions ultimately…
(more)
▼ More than 25% of proteins require metal ion cofactors for structure or function. The interactions between metalloproteins have largely been overlooked, though these interactions ultimately govern metal localization and control metal ion homeostasis. Mammalian metallothionein (MT) is a small, cysteine-rich metalloprotein that binds numerous metal ions per protein strand. Up to seven divalent metals, such as zinc or cadmium, are wrapped into a clustered two-domain structure. This unusually high metal content places MT as an attractive candidate for studying interactions with other metal-binding proteins. This present study investigates the metal transfer reactions between MTs and other metalloproteins, using carbonic anhydrase (CA) as a putative zinc-dependent enzyme.
This thesis presents electrospray ionization mass spectrometric (ESI-MS) data showing the competitive zinc metallation reactions between apoCA and various apoMTs. Modelling of the ESI-MS data is used to determine the reaction parameters and those parameters are shown to be reflected directly in the raw data. These results demonstrate how MT can act as a homeostatic buffer of metal ions, by binding them with different affinities. The kinetics of the metal transfers between zinc MTs and cadmium or zinc CA show that the rates of metal transfer between the two metalloproteins is directly dependent on the metal content of the MT. Further studies on the domain specific properties of MT using shortened MT domain fragment proteins show that: (i) there is no significant degree of domain specificity in metal binding to apoMTs; (ii) the weakest bound metal ion is located within the N-terminal domain of the intact MT protein; (iii) the highest affinity binding site is located within the C-terminal domain; and, (iv) domain-domain interactions within the MT peptide strand modulate metal binding affinities. Taken together, these results support the homeostatic roles of metallothionein proteins while also challenging the mechanisms for metal binding and release to apoenzymes.
Subjects/Keywords: Metal homeostasis; zinc; cadmium; metallothionein; carbonic anhydrase; electrospray ionization mass spectrometry; Analytical Chemistry; Biochemistry; Chemistry; Inorganic Chemistry
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APA (6th Edition):
Pinter, T. B. J. (2015). Reactions between Zinc Metallothionein and Carbonic Anhydrase. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3212
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pinter, Tyler B J. “Reactions between Zinc Metallothionein and Carbonic Anhydrase.” 2015. Thesis, University of Western Ontario. Accessed January 21, 2021.
https://ir.lib.uwo.ca/etd/3212.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pinter, Tyler B J. “Reactions between Zinc Metallothionein and Carbonic Anhydrase.” 2015. Web. 21 Jan 2021.
Vancouver:
Pinter TBJ. Reactions between Zinc Metallothionein and Carbonic Anhydrase. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Jan 21].
Available from: https://ir.lib.uwo.ca/etd/3212.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pinter TBJ. Reactions between Zinc Metallothionein and Carbonic Anhydrase. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/3212
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
18.
Kaluarachchi, Harini.
SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli.
Degree: 2011, University of Toronto
URL: http://hdl.handle.net/1807/31797
► SlyD is a protein involved in [NiFe]-hydrogenase enzyme maturation and, together with HypB and HypA proteins, contributes to the nickel delivery step. To understand the…
(more)
▼ SlyD is a protein involved in [NiFe]-hydrogenase enzyme maturation and, together with HypB and HypA proteins, contributes to the nickel delivery step. To understand the molecular details of this in vivo function, the nickel-binding activity of SlyD was investigated in vitro. SlyD is a monomeric protein that can chelate up to 7 nickel ions with an affinity in the sub-nanomolar range. By truncation and mutagenesis studies we show that the unique C-terminal metal-binding domain of this protein is required for Ni(II) binding and that the protein coordinates this metal non-cooperatively. This activity of SlyD supports the proposed in vivo role of SlyD in nickel homeostasis.
In addition to nickel, SlyD can bind a variety of other types of transition metals. Therefore it was feasible that the protein contributes to homeostasis of metals other than nickel. To test this hypothesis, the metal selectivity of the protein was examined. The preference of SlyD for the metals examined could be ordered as follows, Mn(II), Fe(II) < Co(II) < Ni(II) ~ Zn(II) << Cu(I) indicating that the affinity of SlyD for the different metals follows the Irving-Williams series of metal-complex stabilities. Although the protein is unable to overcome the large thermodynamic preference in vitro for Cu(I) and exclude Zn(II) chelation, in vivo studies suggest a Ni(II)-specific function for the protein.
To understand the function of SlyD as a metallochaperone, its interaction with HypB was investigated. This investigation revealed that SlyD plays a role in Ni(II) storage in E. coli and can function as a Ni(II)-donor to HypB. This study also revealed that SlyD can modulate the metal-binding as well as the GTPase activities of HypB. Based on the experimental data, a role for the HypB-SlyD complex in [NiFe]-hydrogenase biosynthesis is presented.
PhD
Advisors/Committee Members: Zamble, Deborah, Chemistry.
Subjects/Keywords: SlyD; Metal homeostasis; [NiFe]-hydrogenase; Metallochaperone; 0487
…transition metals was investigated in vitro and its role in
metal homeostasis in vivo was examined… …binding to SlyD .. …..
.......33
Figure 2-8
SlyD metal sites can compete with… …103
Figure 4-2
Metal transfer detection via ESI-MS .
113
Figure 4-3… …modulates the high-affinity metal site of HypB …
...116
Figure 4-6
Monitoring metal… …118
Figure 4-7
Metal release from HypB using different acceptors ..
...119…
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APA ·
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APA (6th Edition):
Kaluarachchi, H. (2011). SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/31797
Chicago Manual of Style (16th Edition):
Kaluarachchi, Harini. “SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli.” 2011. Doctoral Dissertation, University of Toronto. Accessed January 21, 2021.
http://hdl.handle.net/1807/31797.
MLA Handbook (7th Edition):
Kaluarachchi, Harini. “SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli.” 2011. Web. 21 Jan 2021.
Vancouver:
Kaluarachchi H. SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli. [Internet] [Doctoral dissertation]. University of Toronto; 2011. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1807/31797.
Council of Science Editors:
Kaluarachchi H. SlyD, A Ni(II) Metallochaperone for [NiFe]-hydrogenase Biosynthesis in Escherichia coli. [Doctoral Dissertation]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/31797
19.
Moulin, Pauline.
Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae.
Degree: Docteur es, Sciences de la Vie et de la Santé, 2017, Université François-Rabelais de Tours
URL: http://www.theses.fr/2017TOUR3308
► Dans cette étude, le transporteur ABC de zinc de Streptococcus agalactiae, première cause d’infections materno-foetale en France, a été caractérisé. Nous avons montré que ce…
(more)
▼ Dans cette étude, le transporteur ABC de zinc de Streptococcus agalactiae, première cause d’infections materno-foetale en France, a été caractérisé. Nous avons montré que ce transporteur se compose, du complexe perméase-ATPase AdcCB, associé à trois protéines membranaires Lmb, AdcA et AdcAII redondantes dans la fixation de zinc. Ce transporteur comporte également deux protéines Sht et ShtII, retrouvées au niveau de la paroi, et nécessaires aux protéines Lmb et AdcAII pour la capture de zinc. L’absence d’un transporteur fonctionnel, par la triple délétion des gènes lmb, adcA et adcAII ou du complexe adcCB, a révélé une inhibition de la croissance et une perturbation de la division de la bactérie lorsqu’elle se trouve dans un environnement carencé en zinc. De plus, nous avons montré que ce transporteur de zinc participe à la survie de la bactérie en milieux biologiques humains, comme le liquide amniotique ou le LCR, où la bactérie est retrouvée lors d’infections, suggérant l’importance du transporteur lors du processus infectieux. Ces résultats ont mis en évidence, pour la première fois, que le zinc assure des fonctions biologiques vitales pour S. agalactiae et que, dans des conditions de forte carence en zinc, le transporteur Adc/Lmb représente le principal système d’acquisition de zinc de la bactérie.
In this study, the zinc-ABC transporter of Streptococcus agalactiae, the first cause of materno-foetal infections in France, was characterized. We showed that this transporter is composed of an AdcCB permease-ATPase complex in association with three membrane-associated proteins Lmb, AdcA and AdcAII, which are redundant in zinc-binding. This transporter also possesses two proteins Sht and ShtII, which are associated to the cell wall, and that are necessary for the Lmb and AdcAII proteins for zinc capture. The absence of a functional transporter, by the triple deletion of the lmb, adcA and adcAII genes or the adcCB complex, revealed a growth inhibition and a disruption of the division of the bacterium when it is in a zinc-restricted environment. Furthermore, we showed that the zinc-ABC transporter contributes to the survival of the bacterium in human biological fluids, as the amniotic fluid or the cerebrospinal fluid, where the bacterium is found during infections, suggesting the importance of the transporter during the infectious process. These results hightlighted, for the first time, that zinc has biologically vital functions in S. agalactiae and that, under high zinc deficiency conditions, the Adc/Lmb transporter is the main zinc acquisition system of the bacterium.
Advisors/Committee Members: Mereghetti, Laurent (thesis director).
Subjects/Keywords: Streptococcus agalactiae; Transporteur ABC; Homéostasie du zinc; Protéine fixatrice de métaux; Streptococcus agalactiae; ABC transporter; Zinc homeostasis; Metal-binding protein
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APA (6th Edition):
Moulin, P. (2017). Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2017TOUR3308
Chicago Manual of Style (16th Edition):
Moulin, Pauline. “Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae.” 2017. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 21, 2021.
http://www.theses.fr/2017TOUR3308.
MLA Handbook (7th Edition):
Moulin, Pauline. “Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae.” 2017. Web. 21 Jan 2021.
Vancouver:
Moulin P. Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2017. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2017TOUR3308.
Council of Science Editors:
Moulin P. Caractérisation du transporteur de zinc Adc/Lmb de Streptococcus agalactiae : Characterization of the ADC/LMB zinc transporter of Streptococcus agalactiae. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2017. Available from: http://www.theses.fr/2017TOUR3308
20.
Hensley, Mart Patrick.
Zinc Homeostasis in E. coli.
Degree: PhD, Chemistry, 2012, Miami University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=miami1333655875
► The homeostasis of transition metal ions is critical to the survival of all organisms. Zinc (Zn(II)) is one of the most important transition metals found…
(more)
▼ The
homeostasis of transition
metal ions is critical
to the survival of all organisms. Zinc (Zn(II)) is one of the most
important transition metals found in biological systems; however,
the
homeostasis of this
metal is poorly understood. Previous
studies have shown that intracellular Zn(II) levels in E. coli are
in the low millimolar range, yet there is less than one “free”
(unbound) Zn(II) ion per cell. There must exist in the E. coli cell
a mechanism for the delivery and insertion of Zn(II) into proteins.
The cytoplasmic transport of other transitions metals, such as
copper, iron, nickel, manganese, and arsenic, is accomplished by a
group of proteins called metallochaperones. No such
metallochaperone has been identified for Zn(II). Since none of the
available models for intracellular Zn(II) transport are able to
explain adequately Zn(II)
homeostasis in E. coli, we hypothesized a
new model. This model proposes that Zn(II) is delivered to Zn(II)
metalloproteins as the proteins are translated and exiting the
ribosome. In the co-translational model for Zn(II)
homeostasis, the
first datum that must be accounted for is the constant presence of
0.2 mM Zn(II) in E. coli. In Chapter 2 it is shown that the
ribosome binds significant amounts of Zn(II). This ribosomal
storage accounts for millimolar amounts of intracellular Zn(II). In
Chapters 3 and 4 studies on several ribosomal proteins (L31, L13,
L22, L24, and L29) are presented in an effort to identify Zn(II)
binding proteins that could transfer Zn(II) to nascent proteins.
Our data show that soluble L31 adopts a unique Zn(II) binding motif
containing one cysteine and histidine. This Zn(II) binding site is
reminiscent of the Cu(I) binding site of ATX1, a copper
metallochaperone. Close examination of the E. coli ribosome crystal
structures shows that L31 does not bind Zn(II) with the same
binding site as in solution. By accounting for all known data about
Zn(II)
homeostasis in E. coli, it is hypothesized that ribosomal
protein L31, while in solution and not bound to the ribosome, acts
as a Zn(II) metallochaperone, delivering Zn(II) to nascent proteins
as they exit the ribosome.
Advisors/Committee Members: Crowder, Michael (Advisor), Makaroff, Christopher (Committee Chair).
Subjects/Keywords: Biochemistry; Zinc homeostasis; metal ion transport
…is not. Metal ion homeostasis has been most extensively studied in
E. coli (12, 23… …of Zn(II) homeostasis is unprecedented in the literature for any metal ion… …and Helman, J., D. (2005) Metal ion homeostasis in Bacillus subtilis. Curr.
Opin… …it is estimated that one out of every three proteins requires
a metal cofactor (1)… …metal ions are essential for the viability of cells; however, these same
metals are toxic if…
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APA ·
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APA (6th Edition):
Hensley, M. P. (2012). Zinc Homeostasis in E. coli. (Doctoral Dissertation). Miami University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=miami1333655875
Chicago Manual of Style (16th Edition):
Hensley, Mart Patrick. “Zinc Homeostasis in E. coli.” 2012. Doctoral Dissertation, Miami University. Accessed January 21, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=miami1333655875.
MLA Handbook (7th Edition):
Hensley, Mart Patrick. “Zinc Homeostasis in E. coli.” 2012. Web. 21 Jan 2021.
Vancouver:
Hensley MP. Zinc Homeostasis in E. coli. [Internet] [Doctoral dissertation]. Miami University; 2012. [cited 2021 Jan 21].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1333655875.
Council of Science Editors:
Hensley MP. Zinc Homeostasis in E. coli. [Doctoral Dissertation]. Miami University; 2012. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1333655875
21.
Sydor, Andrew.
Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA.
Degree: 2013, University of Toronto
URL: http://hdl.handle.net/1807/43738
► The biosynthesis of [NiFe]-hydrogenase and urease in Helicobacter pylori requires several accessory proteins for proper assembly of the nickel-containing active sites. Critical to the maturation…
(more)
▼ The biosynthesis of [NiFe]-hydrogenase and urease in Helicobacter pylori requires several accessory proteins for proper assembly of the nickel-containing active sites. Critical to the maturation of both enzymes in H. pylori is the GTPase HypB. In this work, the metal-binding properties of H. pylori HypB (HpHypB) were investigated and a link between metal binding and the other biochemical properties of HpHypB was established. HpHypB binds stoichiometric nickel or zinc with nanomolar affinities, in partially overlapping sites located between two major GTPase motifs. Upon metal binding, the GTP hydrolysis activity and oligomeric properties of the protein are modulated. Furthermore, the stoichiometry and affinity of the nickel is altered when HpHypB is bound to nucleotide, a change not observed for zinc. Mutagenesis of the metal ligands suggest that a conserved cysteine is responsible for transducing the metal-bound state to altered GTPase activity and a conserved histidine is a required nickel ligand only in the nucleotide-bound state. Together, these results suggest that the metal-binding and GTP hydrolysis properties of HpHypB are intimately linked and may comprise a mechanism through which the [NiFe]-hydrogenase and urease maturation pathways can discriminate between Ni(II) and Zn(II). Characterization of the Escherichia coli GTPase YjiA, a member of the same GTPase family as HpHypB, demonstrated that YjiA can bind Ni(II), Zn(II), or Co(II) at a site in a similar location as in HpHypB. Metal binding also regulates the GTPase activity and oligomerization of YjiA. This finding suggests that metal-responsive GTPase activity may be a trait of this family of GTPases. Together, this work describes a unique link between the metal-binding and biochemical properties of the G3E GTPases and provides insight into the role of HpHypB in [NiFe]-hydrogenase and urease maturation.
PhD
Advisors/Committee Members: Zamble, Deborah, Chemistry.
Subjects/Keywords: bioinorganic; nickel; nickel homeostasis; [NiFe]-hydrogeanse; GTPase; metal homeostasis; metal binding; 0487
…requirements and avoid toxic buildup of the metal, organisms
have evolved complex nickel homeostasis… …Table 2-2
Stoichiometry of metal binding to WT and mutant HpHypB . 53
Table 2-3… …binding to WT, H107A, and C142S HpHypB …. 95
Table 3-8
Stoichiometry of metal binding to WT… …refinement statistics …. 134
Table 4-4
Stoichiometry of metal binding to WT and mutant YjiA… …nickel homeostasis 2
Figure 1-2
Structure of the Escherichia coli NikA…
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APA (6th Edition):
Sydor, A. (2013). Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/43738
Chicago Manual of Style (16th Edition):
Sydor, Andrew. “Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA.” 2013. Doctoral Dissertation, University of Toronto. Accessed January 21, 2021.
http://hdl.handle.net/1807/43738.
MLA Handbook (7th Edition):
Sydor, Andrew. “Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA.” 2013. Web. 21 Jan 2021.
Vancouver:
Sydor A. Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA. [Internet] [Doctoral dissertation]. University of Toronto; 2013. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1807/43738.
Council of Science Editors:
Sydor A. Metal Binding and Response of Helicobacter pylori HypB and Escherichia coli YjiA. [Doctoral Dissertation]. University of Toronto; 2013. Available from: http://hdl.handle.net/1807/43738
Université de Grenoble
22.
Trepreau, Juliette.
Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34.
Degree: Docteur es, Chimie biologie, 2011, Université de Grenoble
URL: http://www.theses.fr/2011GRENV061
► CnrX est un senseur périplasmique, ancré à la membrane, appartenant au complexe CnrYXH qui contribue à réguler l'expression des gènes impliqués dans la résistance au…
(more)
▼ CnrX est un senseur périplasmique, ancré à la membrane, appartenant au complexe CnrYXH qui contribue à réguler l'expression des gènes impliqués dans la résistance au nickel et au cobalt chez Cupriavidus metallidurans CH34. La résistance est induite par la libération de CnrH, un facteur sigma de type ECF (Extracytoplasmic Function), par le complexe CnrYX en réponse à Ni et Co. Nous avons cherché à comprendre la manière dont CnrXs, le domaine senseur de CnrX, détecte les ions métalliques, les stratégies utilisées pour sélectionner spécifiquement Ni ou Co ainsi que la nature du signal engendré par cette interaction. Les techniques spectroscopiques et biophysiques telles que l'UV-visible, la RPE, le XAS et l'ITC ont permis d'étudier les sites métalliques en solution. Le dimère de CnrXs possède quatre sites de liaison au cobalt. Deux des sites (sites F) sont retrouvés dans la protéine entière dont nous avons maintenant un excellent modèle avec le mutant CnrXs-H32A. Les deux autres sites (sites E) ont un signal spectroscopique atypique probablement dû à la formation d'un complexe binucléaire de cobalt. Nous présentons également des structures à haute résolution de CnrXs dans ses formes apo et métallées par le nickel, cobalt ou zinc. Nous avons établi que la forme zinc est la forme inactive de la protéine et que le mécanisme de détection est engendrée par la substitution du zinc par le nickel et le cobalt dans le site F, conduisant à une modification majeure du site de liaison au métal. Tandis que le zinc est pentacoordiné dans une sphère 3N2O, Ni et Co recrutent le soufre de la seule méthionine (Met123) comme sixième ligand pour former un site octaédrique. Nous suggérons que Met123 soit l'interrupteur moléculaire dont la liaison avec le métal fait évoluer la structure de la protéine vers une conformation active. A notre connaissance, ces résultats constituent la première étude structurale et spectroscopique d'un senseur de métal périplasmique impliqué dans un système de transduction du signal dépendant d'un facteur sigma de type ECF.
CnrX is the membrane-anchored periplasmic sensor of the CnrYXH complex that contributes to regulate the expression of the genes involved in cobalt and nickel resistance in Cupriavidus metallidurans CH34. This resistance is induced by the release of the ExtraCytoplasmic Function (ECF) sigma factor CnrH from the CnrYX complex upon sensing of Ni or Co. We addressed the metal sensing mechanisms of CnrXs, the strategies used to select Ni or Co and the nature of the signal onset. Biophysical and spectroscopic techniques allowed us to study the metal binding sites in solution. The CnrXs dimer contains four cobalt binding sites. Two (F sites) are present in the full-length protein which H32A-CnrXs mutant is an excellent model of. The two other sites have an unusual spectroscopic signal that might be due to the formation of a binuclear cobalt complex. We present also high-resolution structures of CnrXs in the apo, Ni-, Co-, and Zn-bound forms. We propose that Zn-bound CnrX typifies the resting state…
Advisors/Committee Members: Covès, Jacques (thesis director), Maillard, Antoine (thesis director).
Subjects/Keywords: Transduction du signal; Homéostasie des métaux (nickel and cobalt; Facteur sigma ECF; Cupriavidus metallidurans CH34; Senseur de métaux; Résistance aux métaux; Signal transduction; Metal homeostasis (nickel/cobalt); ECF sigma factor; Cupriavidus metallidurans CH34; Metal sensor; Metal resistance; 570
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APA (6th Edition):
Trepreau, J. (2011). Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34. (Doctoral Dissertation). Université de Grenoble. Retrieved from http://www.theses.fr/2011GRENV061
Chicago Manual of Style (16th Edition):
Trepreau, Juliette. “Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34.” 2011. Doctoral Dissertation, Université de Grenoble. Accessed January 21, 2021.
http://www.theses.fr/2011GRENV061.
MLA Handbook (7th Edition):
Trepreau, Juliette. “Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34.” 2011. Web. 21 Jan 2021.
Vancouver:
Trepreau J. Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34. [Internet] [Doctoral dissertation]. Université de Grenoble; 2011. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2011GRENV061.
Council of Science Editors:
Trepreau J. Perception du stress métallique (nickel/cobalt) par le système de signalisation transmembranaire Cnr chez Cupriavidus metallidurans CH34 : Metal sensing (nickel/cobalt) by the transmembrane signalisation system Cnr of Cupriavidus metallidurans CH34. [Doctoral Dissertation]. Université de Grenoble; 2011. Available from: http://www.theses.fr/2011GRENV061
23.
Gault, Manon.
L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms.
Degree: Docteur es, Microbiologie, 2014, INSA Lyon
URL: http://www.theses.fr/2014ISAL0130
► Les métaux sont indispensables à la vie cellulaire car ils sont constitutifs des protéines. Les ions Ni, font partie intégrante des hydrogénases, enzymes primordiales pour…
(more)
▼ Les métaux sont indispensables à la vie cellulaire car ils sont constitutifs des protéines. Les ions Ni, font partie intégrante des hydrogénases, enzymes primordiales pour le métabolisme énergétique. Paradoxalement, en excès, les métaux deviennent toxiques pour la cellule. Les bactéries luttent contre cette toxicité en produisant des systèmes de résistance ou d’adaptation. Les cellules procaryotes peuvent équilibrer les teneurs en métaux en contrôlant leur entrée ou leur efflux grâce à la biogenèse de transporteurs spécifiques. L’objectif de ces travaux de thèse a consisté à comprendre les mécanismes principaux permettant à la bactérie modèle Escherichia coli de s’adapter à de fortes variations en ions métalliques, en prenant comme modèle un stress provoqué par un excès d’ions Ni. Afin d’appréhender l’ensemble de la réponse cellulaire, l’effet de ce stress a été évalué sur l’expression de l’ensemble des gènes d’E. coli par des approches de transcriptomique couplées à une validation fonctionnelle. L’excès d’ions Ni induit le système d’efflux RcnRAB. En plus de la pompe d’efflux RcnA, ce système comporte une protéine périplasmique, RcnB, qui module le trafic des ions Ni ou Co via RcnA. Ces travaux ont montré que RcnB n’interagit pas avec les ions Ni ou Co mais de façon inattendue avec les ions Cu, définissant une nouvelle classe de cupro-protéines. Nous montrons que si RcnB n’intervient pas dans le contrôle de l’homéostasie du Cu, l’interaction avec ces ions est essentielle à sa fonction dans la modulation de l’efflux des ions Ni et Co. Ces résultats suggèrent des connexions entre les différents systèmes de maintien des homéostasies métalliques. Les résultats d’analyse transcriptomique montrent une forte modulation de l’expression des gènes impliqués dans les homéostasies du Cu et du Fe en présence d’un excès d’ions Ni, corrélée à une augmentation cellulaire de leur teneur mesurée par spectrométrie plasma. Ces métaux sont responsables de la production d’espèces réactives oxygénées entraînant de sérieux dégâts cellulaires, une des cibles privilégiée étant l’ADN. Nous montrons que les ions Ni ne provoquent pas de cassures de l’ADN et n’ont pas d’effet mutagène, par contre ils provoquent une modification importante de l’état de repliement de l’ADN. Nous proposons que ce relâchement de l’ADN soit dû à l’induction indirecte d’un stress oxydant. Ces travaux ont aboutis à l’identification du premier système de transport spécifique des ions Ni à travers la membrane externe chez E. coli. En résumé, un excès d’ions Ni affecte les systèmes spécifiques d’entrée et d’efflux des ions métalliques troublant les teneurs intracellulaires des autres métaux comme le Cu et le Fe. Ces métaux sont en partie responsables de la production de ROS létaux pour les cellules bactériennes. L’excès de Ni va induire une profonde reprogrammation génétique entraînant des changements physiologiques multifactoriels importants pour la survie bactérienne dans ces conditions de stress.
Metals are necessary components of all living cells because they are…
Advisors/Committee Members: Rodrigue, Agnès (thesis director).
Subjects/Keywords: Biosciences; Microbiologie; Escherichia coli; Métal; Homéostasie; Transcriptome; Mobilité cellulaire; Stress oxydant; Biosciences; Microbiology; Escherichia coli; Metal; Homeostasis; Transcriptome; Cellular mobility; Oxidative stress; DNA - Deoxyribonucleic acid; 579.307 2
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APA ·
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CSE |
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APA (6th Edition):
Gault, M. (2014). L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms. (Doctoral Dissertation). INSA Lyon. Retrieved from http://www.theses.fr/2014ISAL0130
Chicago Manual of Style (16th Edition):
Gault, Manon. “L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms.” 2014. Doctoral Dissertation, INSA Lyon. Accessed January 21, 2021.
http://www.theses.fr/2014ISAL0130.
MLA Handbook (7th Edition):
Gault, Manon. “L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms.” 2014. Web. 21 Jan 2021.
Vancouver:
Gault M. L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms. [Internet] [Doctoral dissertation]. INSA Lyon; 2014. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2014ISAL0130.
Council of Science Editors:
Gault M. L’homéostasie des métaux chez la bactérie Escherichia coli : de l’analyse générale d’un stress sur l’expression des gènes, à la compréhension des mécanismes moléculaires : Metal homeostasis in the bacterium E. coli : from the transcriptomic analysis of a stress, to the understanding of the molecular mechanisms. [Doctoral Dissertation]. INSA Lyon; 2014. Available from: http://www.theses.fr/2014ISAL0130
University of Illinois – Urbana-Champaign
24.
Grillo, Anthony Steven.
Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies.
Degree: PhD, Chemistry, 2017, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/99210
► Traditional approaches in the pharmaceutical industry center around the development of small molecule therapeutics that bind to and inhibit overactive protein function. This has been…
(more)
▼ Traditional approaches in the pharmaceutical industry center around the development of small molecule therapeutics that bind to and inhibit overactive protein function. This has been transformational in the treatment of diseases resulting from an excess of protein function, however, thousands of diseases are alternatively caused by a deficiency of protein function and thus remain incurable. A major subset of these are characterized by mutations in critical ion channels and transporters, such as microcytic anemias, cystic fibrosis, and cardiovascular diseases. Deficiencies of these ion transporting proteins diminish ion flux in distinct sites and directions. Noting the many features that make small molecules advantageous as drugs, we asked can small molecules that imperfectly replicate the function of these missing proteins be sufficient to restore physiology in protein-deficient organisms.
Since the networks of active and passive ion transporting proteins remain active, we hypothesized an imperfect small molecule ion transporter could restore site- and direction-selective transport by leveraging ion gradients that selectively buildup in ion-transport protein deficiencies, thereby restoring physiology to the protein deficient organism. Iron is a critical cofactor in all forms of life, yet its excess is paradoxically toxic. Organisms have thus developed sophisticated homeostatic networks of iron-transport proteins and their regulators to maintain iron at levels sufficient for normal iron-dependent physiological processes without causing ferritoxicity. Acquired or congenital deficiencies of proteins involved in iron transport,
homeostasis, or metabolism often impede the movement of iron into, within, and/or out of cells and are associated with more than 25 Mendelian diseases. We therefore asked whether a small molecule iron transporter could leverage transmembrane gradients of the labile iron pool that selectively build up in such situations to restore the movement of iron into, within, and/or out of cells and thereby enable its use in endogenous iron-dependent physiological processes.
We first used iron-deficient yeast as a discovery platform to find a small molecule candidate. In a modified functional complementation assay, the small molecule natural product, hinokitiol, restored growth to yeast missing the iron transporting complex Fet3Ftr1. Hinokitiol promoted iron uptake, and concomitantly restored cell growth back to wild-type levels. In contrast to water soluble iron chelators, hinokitiol:iron complexes are lipid soluble, and readily diffuse through lipid membranes. Extensive biophysical studies suggest this growth restoration can be attributed to the capacity for hinokitiol to promote the transmembrane transport of iron.
Encouraged by these results, we next tested the capacity for hinokitiol to promote gut iron absorption and/or hemoglobinization in cells and animals missing three different iron-transport proteins by promoting iron mobilization and utilization. Hinokitiol restored the uptake and…
Advisors/Committee Members: Burke, Martin D (advisor), Burke, Martin D (Committee Chair), Denmark, Scott E (committee member), Mitchell, Douglas A (committee member), Zimmerman, Steven C (committee member).
Subjects/Keywords: Hinokitiol; Iron transport; Divalent metal transporter 1 (DMT1); Ferroportin-1 (FPN1); Mitoferrin 1 (MFRN1); Small molecule iron transporter; Iron transporter; Molecular prosthetic; Molecular prosthetics; Iron biology; Hemoglobinization; Iron homeostasis
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Grillo, A. S. (2017). Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99210
Chicago Manual of Style (16th Edition):
Grillo, Anthony Steven. “Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 21, 2021.
http://hdl.handle.net/2142/99210.
MLA Handbook (7th Edition):
Grillo, Anthony Steven. “Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies.” 2017. Web. 21 Jan 2021.
Vancouver:
Grillo AS. Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/2142/99210.
Council of Science Editors:
Grillo AS. Restored iron transport by a small molecule promotes absorption and hemoglobinization: discovery, development, and mechanistic studies. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99210
Georgia State University
25.
Toukoki, Chadia.
MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus.
Degree: PhD, Biology, 2009, Georgia State University
URL: https://scholarworks.gsu.edu/biology_diss/66
► Group A Streptococcus (GAS) is a common pathogen of the human skin and mucosal surfaces and is capable of producing a variety of diseases. This…
(more)
▼ Group A Streptococcus (GAS) is a common pathogen of the human skin and mucosal surfaces and is capable of producing a variety of diseases. This dissertation investigates the function of a metalloregulator named MtsR in GAS physiology and disease process. An mtsR mutant was constructed and analyzed. Consistent with MtsR role in iron uptake regulation, the mtsR mutant accumulates more iron (80 ± 22.5%) than the wild type strain. Inactivation of mtsR results in
constitutive transcription of the sia (Streptococcal Iron Acquisition) operon, which is negatively regulated by iron in the parent strain. We identified the promoter that controls the expression of the sia operon (Pshr) and used it as a model to study MtsR interaction with DNA. Electrophoretic mobility gel shift assays (EMSAs) demonstrated that MtsR binds to the shr upstream region specifically and in an iron and manganese dependent manner. DNase I footprint analysis revealed that MtsR protects a 69 bp segment in Pshr that includes 2 inverted repeats, overlapping the core promoter elements. A global transcriptional analysis determined that MtsR modulates
the expression of 64 genes, of which 44 were upregulated and 20 were downregulated in the
mtsR mutant. MtsR controls genes with diverse functions including immune evasion, colonization, dissemination,
metal homeostasis, nucleic acid and amino acid metabolism, and protein stability. MtsR functions as a dual regulator as it binds to the promoters of the repressed genes ska, aroE, and nrdF.2, as well as the upstream region of the positively regulated genes mga, emm49, and pyrF. A 16 bp MtsR-binding consensus region was identified in all of the
promoters that are directly regulated by MtsR. In conclusion, we have demonstrated that MtsR
is a global regulator in GAS that controls the expression of vital virulence factors and genes
involved in
metal transport, virulence and metabolic pathways.
Advisors/Committee Members: Zehava Eichenbaum - Chair, John Houghton, Chung-Dar Lu, Phang C. Tai.
Subjects/Keywords: Iron regulation; Sia operon; Metal homeostasis; Virulence; Microarray; Streptococcus pyogenes; Biology
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APA (6th Edition):
Toukoki, C. (2009). MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus. (Doctoral Dissertation). Georgia State University. Retrieved from https://scholarworks.gsu.edu/biology_diss/66
Chicago Manual of Style (16th Edition):
Toukoki, Chadia. “MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus.” 2009. Doctoral Dissertation, Georgia State University. Accessed January 21, 2021.
https://scholarworks.gsu.edu/biology_diss/66.
MLA Handbook (7th Edition):
Toukoki, Chadia. “MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus.” 2009. Web. 21 Jan 2021.
Vancouver:
Toukoki C. MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus. [Internet] [Doctoral dissertation]. Georgia State University; 2009. [cited 2021 Jan 21].
Available from: https://scholarworks.gsu.edu/biology_diss/66.
Council of Science Editors:
Toukoki C. MTSR is a Dual Regulator that Controls Virulence Genes and Metabolic Functions in Addition to Metal Homeostasis in Group A Streptococcus. [Doctoral Dissertation]. Georgia State University; 2009. Available from: https://scholarworks.gsu.edu/biology_diss/66
Miami University
26.
Sigdel, Tara.
A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches.
Degree: PhD, Chemistry, 2005, Miami University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584
► Zinc is a transition metal that exists exclusively in the +2 oxidation state in biological systems (Zn(II)). Zn(II) serves as a catalytic cofactor in members…
(more)
▼ Zinc is a transition
metal that exists exclusively in
the +2 oxidation state in biological systems (Zn(II)). Zn(II)
serves as a catalytic cofactor in members from all classes of
enzymes and as a structural component in dozens of proteins.
Despite being essential for the structural/catalytic properties of
many cellular proteins, excess Zn(II) is toxic to cells. Recent
reports demonstrate that E. coli cells contain low millimolar
concentrations of Zn(II); however, subsequent studies reveal that
there are no pools of free Zn(II) in the cytoplasm of the cell.
Several groups have hypothesized the existence of
Zn(II)-metallochaperones, which bind and deliver Zn(II) ions;
however, no such proteins have yet been identified. This
dissertation describes our efforts to identify the
Zn(II)-responsive proteins in E. coli by using proteomics (2D gels
coupled with peptide identification) and genomics (cDNA
microarrays). Proteomic studies identified a number of proteins
with differential expression levels in response to extracellular
Zn(II) levels; however, none of the identified proteins have
previously been associated with Zn(II) transport. cDNA microarrays
identified a number of differentially-expressed transcripts in
response to stress by Zn(II) excess and deficiency, and several of
the corresponding proteins were hypothesized to be
Zn(II)-metallochaperones. One candidate protein, YodA, was cloned,
over-expressed, and used as bait in a pulldown assay. Comparisons
of results from the proteomic and genomic approaches demonstrate a
surprising lack of consistency, which indicates that caution should
be used when applying these techniques to study global protein/RNA
changes in response to external stimuli. In summary, this
dissertation describes an approach to probe for the Zn(II)
metallome of an organism, and this approach can be extended to
other organisms to better understand the homeostatic pathways used
to maintain intracellular
metal ion concentrations.
Advisors/Committee Members: Crowder, Michael (Advisor).
Subjects/Keywords: E. Coli; Zinc transport and homeostasis; Proteomics; cDNA microarray; 2D gel; metal transport
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APA ·
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MLA ·
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CSE |
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APA (6th Edition):
Sigdel, T. (2005). A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches. (Doctoral Dissertation). Miami University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584
Chicago Manual of Style (16th Edition):
Sigdel, Tara. “A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches.” 2005. Doctoral Dissertation, Miami University. Accessed January 21, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584.
MLA Handbook (7th Edition):
Sigdel, Tara. “A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches.” 2005. Web. 21 Jan 2021.
Vancouver:
Sigdel T. A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches. [Internet] [Doctoral dissertation]. Miami University; 2005. [cited 2021 Jan 21].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584.
Council of Science Editors:
Sigdel T. A Search for Zn(II) Metallochaperones in E. coli, Proteomic
and Genomic Approaches. [Doctoral Dissertation]. Miami University; 2005. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584
27.
Nery, Camille Reyes.
Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae.
Degree: Biochemistry & Molecular Biology, 2013, UCLA
URL: http://www.escholarship.org/uc/item/34r7x122
► The transition metals iron and zinc are essential requirements for all living organisms. They participate in a variety of critical metabolic pathways, enzymatic activity, and…
(more)
▼ The transition metals iron and zinc are essential requirements for all living organisms. They participate in a variety of critical metabolic pathways, enzymatic activity, and provide structural support for countless proteins. Metal ion imbalance can be detrimental to organisms, as metal deficiency can alter many biological processes while metal excess can lead to toxicity. To alleviate these detrimental situations, the yeast Saccharomyces cerevisiae has developed tightly controlled regulatory mechanisms for the proper expression of proteins that control import, export, and storage of these essential metals. This regulation is required to ensure the efficient uptake, transport, and storage of specific metal ions during periods of metal concentration fluctuations. The work presented in the first chapter of this dissertation identifies the use of cryptic transcription as a means for regulatory control of the subtelomeric metal genes ZRT1 and FIT3. These transcripts arise from promoter units upstream of the ZRT1/FIT3 transcription unit and extend into the open reading frame (ORF). We show that these transcripts are degraded by the cytoplasmic Non-Sense Mediated Decay (NMD) Pathway and are only stabilized in the absence of the NMD Pathway; hence termed Cytoplasmically Degraded Cryptic Unstable Transcripts (CD-CUTs). We further show that these CD-CUTs act to prevent expression of ZRT1 by interfering with RNA polymerase II binding and activator binding (Zap1p) to the ZRT1 promoter unit. As we identified the use of CD-CUTs to mediate the repression of ZRT1/FIT3 during normal zinc/iron conditions, the mechanistic mode of action of these transcripts remained elusive. In an attempt to identify how a cytoplasmically degraded transcript can mediate transcription in the nucleus, we chose to study the cytoplasmic trafficking of these species. In chapter two, we show that the export of the ZRT1/FIT3 CD-CUTs is likely mediated by the SR-type mRNA export factor Hrb1p and dependent on the essential mRNA export factor Mex67p. Lastly, we identify an additional mode of regulation for the iron transport gene FIT3 by the glucose repressor Mig1p. Mig1p has been extensively characterized as a repressor of glucose responsive genes and in chapter three, we show that this regulation can be applied to iron regulation. We believe that Mig1p regulates the repression of FIT3 during conditions of normal iron and/or after switch back to normal iron conditions following iron starvation to prevent the deleterious expression of FIT3, thereby preventing the potentially harmful effects of iron toxicity.
Subjects/Keywords: Biochemistry; Molecular biology; Cryptic Transcription; FIT3; Glucose repressor; Metal Homeostasis; Metal Transport Genes; mRNA export
…of Metal Homeostasis
Genes (PloS Genetics, 2011). Many thanks to PloS Genetics… …Mediates Repression of Subtelomeric Metal Homeostasis Genes,
PLoS Genetics 7(6)… …Cryptic Transcription Mediates Transcription of Metal
Homeostasis Genes
1… …intergenic regions lie upstream of many
subtelomeric genes involved in metal homeostasis; namely… …used as a
mechanism for regulatory control of genes involved in metal homeostasis and not…
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APA (6th Edition):
Nery, C. R. (2013). Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/34r7x122
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Nery, Camille Reyes. “Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae.” 2013. Thesis, UCLA. Accessed January 21, 2021.
http://www.escholarship.org/uc/item/34r7x122.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nery, Camille Reyes. “Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae.” 2013. Web. 21 Jan 2021.
Vancouver:
Nery CR. Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae. [Internet] [Thesis]. UCLA; 2013. [cited 2021 Jan 21].
Available from: http://www.escholarship.org/uc/item/34r7x122.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nery CR. Novel Repression Mechanisms for Metal Transport Genes in Saccharomyces cerevisiae. [Thesis]. UCLA; 2013. Available from: http://www.escholarship.org/uc/item/34r7x122
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Michigan
28.
Passalacqua, Karla Diane.
Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis.
Degree: PhD, Microbiology, 2007, University of Michigan
URL: http://hdl.handle.net/2027.42/126958
► Bacillus anthracis, the causative agent of the disease anthrax, is a gram-positive bacterium found in soil habitats worldwide and exists in two morphologies: infectious, inert…
(more)
▼ Bacillus anthracis, the causative agent of the disease anthrax, is a gram-positive bacterium found in soil habitats worldwide and exists in two morphologies: infectious, inert spores and replicative vegetative bacilli. We hypothesize that protective antioxidant enzymes and
metal uptake systems contribute to bacterial fitness during the establishment of disease. We undertook in vitro physiological studies of B. anthracis on both global and local scales to define the roles that superoxide dismutases (SODs) play in this microbe's biology and to better characterize the connection between bacterial oxidative stress and
metal ion
homeostasis. The creation of multiple sod deletion (Deltasod ) mutants showed that of the four putative B. anthracis sods, sodA1 encodes the predominantly active enzyme responsible for protection from oxidative insults. The SODA1 and SODA2 paralogs form active homodimers and heterodimers, but only slight physiological redundancy exists between the two. A third paralog, SOD15, is differentially expressed upon entry into stationary/sporulation phase, and is a member of a four-gene operon that may be involved in bacterial morphology. However, the SODs are not essential for survival within a mouse model of inhalational anthrax. The global transcriptional profiles of B. anthracis to physiological redox perturbations imposed by hydrogen peroxide and paraquat showed that whereas hydrogen peroxide results in a response mainly defined by DNA metabolism, endogenous superoxide elicits a response indicative of
metal ion
homeostasis imbalances. B. anthracis produces two iron-chelating siderophores: petrobactin and bacillibactin. We found that transcriptional control of the genes needed for synthesis of these two metabolites is unique, and that end-point metabolite yields vary depending on
metal availability and oxygenation. Lastly, we found that manganese availability protects B. anthracis from oxidative damage to proteins, and that mutants lacking both sodA1 and sodA2 are sensitive to manganese and iron limitation, connecting antioxidant capability,
metal homeostasis, and metabolic efficiency. These in vitro observations shed light on the multiple physiological capabilities of B. anthracis and reveal the many ways that this microorganism is able to efficiently establish disease.
Advisors/Committee Members: Hanna, Philip C. (advisor).
Subjects/Keywords: Anthrax; Approaches; Bacillus Anthracis; Bacterial; Characterization; Global; Local; Metal Ion Homeostasis; Microarrays; Oxidative Stress; Siderophores; Study; Superoxide Dismutases
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❌
APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Passalacqua, K. D. (2007). Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/126958
Chicago Manual of Style (16th Edition):
Passalacqua, Karla Diane. “Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis.” 2007. Doctoral Dissertation, University of Michigan. Accessed January 21, 2021.
http://hdl.handle.net/2027.42/126958.
MLA Handbook (7th Edition):
Passalacqua, Karla Diane. “Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis.” 2007. Web. 21 Jan 2021.
Vancouver:
Passalacqua KD. Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis. [Internet] [Doctoral dissertation]. University of Michigan; 2007. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/2027.42/126958.
Council of Science Editors:
Passalacqua KD. Characterization of the superoxide dismutases of Bacillus anthracis: Global and local approaches to the study of bacterial oxidative stress and metal ion homeostasis. [Doctoral Dissertation]. University of Michigan; 2007. Available from: http://hdl.handle.net/2027.42/126958
IUPUI
29.
LeVora, Jennifer K.
THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS.
Degree: 2012, IUPUI
URL: http://hdl.handle.net/1805/3177
► Indiana University-Purdue University Indianapolis (IUPUI)
The etiology of many neurodegenerative diseases is unknown, but a number of studies indicate that a combination of both genetic…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
The etiology of many neurodegenerative diseases is unknown, but a number of studies indicate that a combination of both genetic and environmental factors contribute to the progression of disease. Exposure to environmental metals, such as Mn2+, Fe2+, Cu2+, and Al3+, has been shown to increase cell death that is characteristic of neurodegenerative disorders such as AD, PD, Wilson’s disease and Menkes disease. These metals are important in numerous biological processes in the brain and their homeostasis is regulated through multiple mechanisms of transport, storage, and secretion. The vertebrate divalent metal transporter-1 (DMT-1) has been implicated in transport and homeostasis of these divalent cations. In these studies I utilize Caenorhabditis elegans (C. elegans) to show that long term exposure to Mn2+ decreases animal viability in a dose-dependent manner, and I demonstrate that C. elegans homologues to DMT-1, SMF-1, SMF-2, and SMF-3, play specific roles in divalent metal ion-induced DA neurodegeneration. I show that SMF-1 contributes to Fe2+-induced DA neuron degeneration, SMF-3 contributes to Al3+-induced DA neuron degeneration, and both SMF-2 and DAT-1 contribute to Cu2+-induced DA neuron cell death. These studies utilize C. elegans as a powerful model to characterize molecules and pathways involved in metal toxicity and metal-induced DA neuron degeneration.
Advisors/Committee Members: Nass, Richard M., Nicol, Grant D., Hingtgen, Cynthia M., 1966-.
Subjects/Keywords: dopamine; C. elegans; SMF; aluminum; copper; Parkinson's Disease; Dopamine; Neurotoxicology; Cell death; Parkinson's disease; Metal ions – Physiological effect; Nervous system – Degeneration – Molecular aspects; Oxidative stress; Metals – Toxicology; Homeostasis; Caenorhabditis elegans; Mitochondrial pathology; Copper – Physiological effect; Hepatolenticular degeneration; Alzheimer's disease
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
LeVora, J. K. (2012). THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/3177
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
LeVora, Jennifer K. “THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS.” 2012. Thesis, IUPUI. Accessed January 21, 2021.
http://hdl.handle.net/1805/3177.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
LeVora, Jennifer K. “THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS.” 2012. Web. 21 Jan 2021.
Vancouver:
LeVora JK. THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS. [Internet] [Thesis]. IUPUI; 2012. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1805/3177.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
LeVora JK. THE ROLE OF SMF 1, SMF-2, SMF-3 IN METAL-INDUCED WHOLE ANIMAL VULNERABILITY AND DOPAMINE NEURON DEGENERATION IN CAENORHABDITIS ELEGANS. [Thesis]. IUPUI; 2012. Available from: http://hdl.handle.net/1805/3177
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Duke University
30.
Haas, Kathryn Louise.
Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
.
Degree: 2010, Duke University
URL: http://hdl.handle.net/10161/2373
► Mechanisms of copper homeostasis are of great interest partly due to their connection to debilitating genetic and neurological disorders. The family of high-affinity copper…
(more)
▼ Mechanisms of copper
homeostasis are of great interest partly due to their connection to debilitating genetic and neurological disorders. The family of high-affinity copper transporters (Ctr) is responsible for extracellular copper acquisition and internalization in yeast, plants, and mammals, including human. The extracellular domain of the human high-affinity copper transporter (hCtr1) contains essential Cu-binding methionine-rich MXXM and MXM (Mets) motifs that are important for copper acquisition and transport. The hCtr1 extracellular domain also contains potential copper binding histidine (His) clusters, including a high-affinity Cu(II) ATCUN site. As of yet, extracellular His clusters have no established significance for hCtr1 function. We have made model peptides based on the extracellular copper acquisition domain of hCtr1 that is rich in His residues and Mets motifs. The peptides' Cu(I) and Cu(II) binding properties have been characterized by UV-Vis and mass spectrometry. Our findings have been extended to a mouse cell model and we show that His residues are important for hCtr1 function likely because of their contribution to strong copper-binding sites in the hCtr1 extracellular domain responsible for copper acquisition.
Copper's pro-oxidant property is also medicinally promising if it can be harnessed to induce oxidative stress as a cancer chemotherapy strategy. Our lab has designed a photocleavable caged copper complex that can selectively release redox-active copper in response to light. The thermodynamic copper binding properties of these potential chemotherapeutics have been characterized
Advisors/Committee Members: Franz, Katherine J (advisor).
Subjects/Keywords: Chemistry, Inorganic;
Chemistry, Biochemistry;
Caged Copper;
Copper;
Copper Transport;
Ctr1;
Membrane Protein;
Metal Homeostasis
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Haas, K. L. (2010). Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/2373
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Haas, Kathryn Louise. “Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
.” 2010. Thesis, Duke University. Accessed January 21, 2021.
http://hdl.handle.net/10161/2373.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Haas, Kathryn Louise. “Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
.” 2010. Web. 21 Jan 2021.
Vancouver:
Haas KL. Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
. [Internet] [Thesis]. Duke University; 2010. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10161/2373.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Haas KL. Copper at the Interface of Chemistry and Biology: New Insights into hCtr1 Function and the Role of Histidine in Human Cellular Copper Acquisition
. [Thesis]. Duke University; 2010. Available from: http://hdl.handle.net/10161/2373
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
◁ [1] [2] ▶
. 
Open Access Theses and Dissertations
