subject:(Multidrug resistance associated protein 4)

Queens University

1. Miah, Mohammad Fahad. Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) .

Degree: Pathology and Molecular Medicine, 2015, Queens University

URL: http://hdl.handle.net/1974/13589

► Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. In polarized cells, MRP4 localizes… (more)

▼ Multidrug resistance protein 4 (MRP4) is a member of subfamily C of the ATP-binding cassette superfamily of membrane transport proteins. In polarized cells, MRP4 localizes to the apical or basolateral plasma membrane depending on the tissue type. To gain insight into mechanisms regulating MRP4 plasma membrane trafficking, its interactions with the PDZ domain-containing CortBP1, a member of Shank2 family of adapter proteins, were investigated. Since CortBP1 is known to recruit proteins involved in endocytosis, it was hypothesized that CortBP1 plays a role in MRP4 internalization from the plasma membrane. Ectopic expression of CortBP1 led to decreased total MRP4 levels in HEK293T cells and cell surface biotinylation experiments and confocal microscopy showed that this decrease was at the plasma membrane. Pull-down experiments indicated that the interaction between CortBP1 and MRP4 requires the last four amino acids 1322ETAL of the transporter. They also suggested that MRP4 may exist in a complex with CortBP1 and endocytic proteins. In SH-SY5Y and BE(2)-C human neuroblastoma cells, RNAi-mediated knockdown of endogenous SHANK2 isoforms (including CORTBP1) resulted in increased total MRP4 levels. Confocal microscopy of SHANK2-depleted BE(2)-C cells suggested that this increase occurred at the plasma membrane. These observations demonstrate that the internalization of plasma membrane MRP4 is regulated by CortBP1, and possibly other SHANK2 family members. In addition to PDZ domain-containing adapter proteins, N-glycans can regulate the apical membrane localization of some proteins. Whether this is true for MRP4 is unknown. Based on in silico analyses and topological models of human MRP4, it was hypothesized that it is glycosylated at Asn746 and Asn754. Single substitutions of these Asn residues with Gln (N746Q, N754Q) increased the electrophoretic mobility of MRP4; double substitutions (N746/754Q) increased its mobility further such that it was comparable to wild-type MRP4 deglycosylated with PNGase F. Importantly, confocal microscopy indicated that the apical membrane localization of the single and double Asn mutants in polarized LLC-PK1 cells was comparable to wild-type MRP4. This suggests that N-glycans are not required for apical membrane localization of MRP4, at least in LLC-PK1 cells. Overall, the results of these studies provide novel insights into the membrane trafficking of MRP4.

Subjects/Keywords: Multidrug Resistance Protein 4 ; Membrane Protein Trafficking

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Miah, M. F. (2015). Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/13589

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Miah, Mohammad Fahad. “Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) .” 2015. Thesis, Queens University. Accessed April 10, 2021. http://hdl.handle.net/1974/13589.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Miah, Mohammad Fahad. “Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) .” 2015. Web. 10 Apr 2021.

Vancouver:

Miah MF. Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) . [Internet] [Thesis]. Queens University; 2015. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1974/13589.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Miah MF. Investigations into the Plasma Membrane Trafficking of Multidrug Resistance Protein 4 (ABCC4/MRP4) . [Thesis]. Queens University; 2015. Available from: http://hdl.handle.net/1974/13589

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Carillion, Aude. Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom.

Degree: Docteur es, Physiologie et Physiopathologie, 2015, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2015PA066485

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Les travaux présentés dans ce mémoire ont pour objectif d’approfondir la compréhension de l’altération de la réponse à la stimulation des récepteurs β-adrénergiques dans plusieurs… (more)

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Les travaux présentés dans ce mémoire ont pour objectif d’approfondir la compréhension de l’altération de la réponse à la stimulation des récepteurs β-adrénergiques dans plusieurs contextes physiopathologiques. La première étude confirme l’existence d’une dysfonction β-adrénergique à l’échelle du cardiomyocyte au cours de la sénescence. Elle met en lumière le rôle de la protéine MRP4 (multidrug resistance associated protein 4) dans cette diminution de réponse inotrope positive à l’isoprotérénol. La deuxième étude évalue la réponse à la stimulation des récepteurs β-adrénergiques dans le syndrome métabolique et montre que la dysfonction est modérée dans ce contexte même en cas de diabète associé à l’obésité. Ces résultats fonctionnels sont expliqués par la diminution d’expression des récepteurs β1- et β2-adrénergiques mais l’absence de surexpression du récepteur β3-adrénergique comme observée dans le diabète de type 1. La troisième étude analyse le rôle de l’atorvastatine sur la réponse β-adrénergique chez les diabétiques et les mécanismes de modulation de cette réponse par une étude du transcriptome cardiaque. Elle montre également que l’inhibition de la production d’oxyde nitrite améliore la réponse β-adrénergique. La quatrième étude a expliqué une part de la dysfonction β-adrénergique chez les diabétiques par la surexpression de MRP4. L’inhibition de MRP4 a permis de restaurer la réponse à l’isoprotérénol au cours de la cardiopathie diabétique. Au total, l’ensemble de nos travaux poursuit la description des mécanismes de la dysfonction β-adrénergique dans la sénescence et le diabète et souligne le rôle de MRP4.

The studies presented in this report looked for a better understanding of the altered response to stimulation of the β-adrenergic receptors in several physiopathological contexts. The first study confirms the alteration of the β-adrenergic response at the cardiomyocyte level in the senescent cardiomyopathy. The role of MRP4 (multidrug resistance associated protein 4) in the reduced inotropic response to isoproterenol is emphasized. The second study evaluates the response to β-adrenoceptors stimulation in the metabolic syndrome and shows mild dysfunction in this context even in obesity associate with diabetes. These functional results are explained by a reduced expression of β1- and β2-adrenergic receptors but no overexpression of β3-adrenoceptor as observed in type 1 diabetes. The third study analyzes the role of atorvastatin on the β-adrenergic response in the diabetic cardiomyopathy and the mechanisms involved by study of the cardiac transcriptome. The inhibition of nitrite oxide production improves the response to β-adrenoceptors stimulation in diabetic heart. The fourth study explained part of the β-adrenergic dysfunction in the diabetic cardiomyopathy by the overexpression of MRP4. The inhibition of this protein restored the response to isoproterenol during diabetic cardiomyopathy. All together the present results carry on with description of the mechanisms involved in the β-adrenergic dysfunction in…

Advisors/Committee Members: Amour, Julien (thesis director), Riou, Bruno (thesis director).

Subjects/Keywords: Stimulation β-adrénergique; Sénescente; Cardiopathie diabétique; Syndrome métabolique; Multidrug resistance associated protein 4; MRP4; Βeta-adrenergic stimulation; Aging; 572.4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Carillion, A. (2015). Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2015PA066485

Chicago Manual of Style (16^th Edition):

Carillion, Aude. “Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom.” 2015. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed April 10, 2021. http://www.theses.fr/2015PA066485.

MLA Handbook (7^th Edition):

Carillion, Aude. “Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom.” 2015. Web. 10 Apr 2021.

Vancouver:

Carillion A. Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. [cited 2021 Apr 10]. Available from: http://www.theses.fr/2015PA066485.

Council of Science Editors:

Carillion A. Physiopathologie de la dysfonction bêta-adrénergique et rôle de la protéine MRP4 au cours du vieillissement, du diabète et du syndrome métabolique : Physiopathology of beta-adrenergic dysfunction and role of MRP4 during aging, diabetes mellitus and metabolic syndrom. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. Available from: http://www.theses.fr/2015PA066485

Texas State University – San Marcos

3. Freeman, Kris Ray. Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum.

Degree: MS, Biology, 2013, Texas State University – San Marcos

URL: https://digital.library.txstate.edu/handle/10877/6336

► Multidrug resistance protein 4 (MRP4) is a transmembrane efflux protein capable of substrate-specific transport of endogenous and xenobiotic molecules across the cell membrane, including several… (more)

Subjects/Keywords: MRP4; Multidrug Resistance Protein 4; Proteomic; Knockout; Biomarkers; Inflammation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Freeman, K. R. (2013). Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum. (Masters Thesis). Texas State University – San Marcos. Retrieved from https://digital.library.txstate.edu/handle/10877/6336

Chicago Manual of Style (16^th Edition):

Freeman, Kris Ray. “Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum.” 2013. Masters Thesis, Texas State University – San Marcos. Accessed April 10, 2021. https://digital.library.txstate.edu/handle/10877/6336.

MLA Handbook (7^th Edition):

Freeman, Kris Ray. “Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum.” 2013. Web. 10 Apr 2021.

Vancouver:

Freeman KR. Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum. [Internet] [Masters thesis]. Texas State University – San Marcos; 2013. [cited 2021 Apr 10]. Available from: https://digital.library.txstate.edu/handle/10877/6336.

Council of Science Editors:

Freeman KR. Proteomic Comparison Between Mrp4 Knockout and Wild Type Mouse Brain, Liver, Kidney and Serum. [Masters Thesis]. Texas State University – San Marcos; 2013. Available from: https://digital.library.txstate.edu/handle/10877/6336

University of the Western Cape

4. Witbooi, Christopher Jerome. In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates .

Degree: 2015, University of the Western Cape

URL: http://hdl.handle.net/11394/5347

► Retinoblastoma Binding Protein 6 (RBBP6) is a RING finger-containing protein which plays a critical role in the 3'-end processing of mRNA transcripts. It is a… (more)

▼ Retinoblastoma Binding Protein 6 (RBBP6) is a RING finger-containing protein which plays a critical role in the 3'-end processing of mRNA transcripts. It is a constituent of the human pre-mRNA processing complex but also interacts directly with core splicing-associated proteins. RBBP6 also interacts with both major tumour suppressor proteins p53 and pRb and is known to play a critical role in suppression of p53 during development, in cooperation with MDM2. Through its RING finger it interacts with the C-terminus of the oncogenic protein Y-Box Binding Protein 1 (YB-1) both in vitro and in vivo, catalysing its ubiquitination and degradation in the proteasome. YB-1 is closely associated with tumour progression, poor patient prognosis and chemotherapeutic resistance, making it a promising target for therapeutic intervention. Unpublished data from our laboratory suggests that RBBP6 is able to poly-ubiquitinate YB-1 in vitro, using UbcH1 as the ubiquitin- conjugating enzyme (E2). This study aims to identify RBBP6 RING protein-protein interactions involved in the down regulation of YB-1 by RBBP6. These interactions include the C-terminal fragment of YB-1 (substrate), MDM2 (E3) and UbcH1 (E2). The C-terminal fragment of YB-1, denoted YB-1₂₂₀₋₃₂₄, was successfully cloned and expressed in bacteria and demonstrated to interact directly with the RBBP6 RING finger domain in in vitro affinity pull down assays. This is in good agreement with our unpublished data that RBBP6 is able to ubiquitinate full length YB-1 as well as the YB-1₂₂₀₋₃₂₄ fragment. UbcH1 was successfully expressed and shown to interact directly with RBBP6 RING in in vitro affinity pull down assays. This is also in agreement with our data showing that RBBP6 is able to ubiquitinate YB-1 using UbcH1 as E2. ¹⁵N-labelled samples of RBBP6 RING was successfully expressed in bacteria and used to investigate the putative interaction with UbcH1 in NMR-based chemical shift perturbation assays. However no interaction was observed, possibly because the sample of UbcH1 was subsequently found using mass spectrometery to be partially degraded. GST-tagged RBBP6 RING was able to precipitate MDM2 from HeLa lysate. This extends previous reports that full length RBBP6 and MDM2 interact directly and play a role in the suppression of p53 during development. The result was validated by showing that GST-MDM2 was able to precipitate RBBP6 RING in in vitro. This study includes a side project which involved the cloning and expression of DWNN-GG. GST-HADWNN-GG was successfully cloned and expressed in bacteria. An HA tag was included immediately upstream of DWNN-GG for immunodetection using anti-HA antibodies; the construct was designed in such as way that it could be re-used to generate HA-tagged versions of existing constructs cloned into pGEX-6P-2. The above findings lay the foundation for future structural and functional studies of the involvement of RBBP6 in regulation of the cancer-related proteins p53 and YB-1, which may have far-reaching consequences in the fight against cancer. Advisors/Committee Members: Pugh, David J.R (advisor).

Subjects/Keywords: Retinoblastoma Binding Protein 6 (RBBP6); Cancer; Ubiquitination; ; Polymerase chain reaction; Multidrug Resistance-Associated Proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Witbooi, C. J. (2015). In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/5347

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Witbooi, Christopher Jerome. “In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates .” 2015. Thesis, University of the Western Cape. Accessed April 10, 2021. http://hdl.handle.net/11394/5347.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Witbooi, Christopher Jerome. “In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates .” 2015. Web. 10 Apr 2021.

Vancouver:

Witbooi CJ. In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates . [Internet] [Thesis]. University of the Western Cape; 2015. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/11394/5347.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Witbooi CJ. In vitro investigation of putative interactions between the RING finger domain of Retinoblastoma Binding Protein 6 (RBBP6) and various substrates . [Thesis]. University of the Western Cape; 2015. Available from: http://hdl.handle.net/11394/5347

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. ZHANG JING. Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines.

Degree: 2009, National University of Singapore

URL: http://scholarbank.nus.edu.sg/handle/10635/16338

Subjects/Keywords: cyclophosphamide; ifosfamide; multidrug-associated protein 4(MRP4/ABCC4)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

JING, Z. (2009). Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/16338

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

JING, ZHANG. “Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines.” 2009. Thesis, National University of Singapore. Accessed April 10, 2021. http://scholarbank.nus.edu.sg/handle/10635/16338.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

JING, ZHANG. “Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines.” 2009. Web. 10 Apr 2021.

Vancouver:

JING Z. Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines. [Internet] [Thesis]. National University of Singapore; 2009. [cited 2021 Apr 10]. Available from: http://scholarbank.nus.edu.sg/handle/10635/16338.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

JING Z. Role of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the resistance and toxicity of oxazaphosphorines. [Thesis]. National University of Singapore; 2009. Available from: http://scholarbank.nus.edu.sg/handle/10635/16338

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Technology, Sydney

6. Lu, Jamie Fung. Microparticles mediate trait dominance in cancer.

Degree: 2015, University of Technology, Sydney

URL: http://hdl.handle.net/10453/44200

► Multidrug resistance (MDR) persists to be a major hindrance to the successful treatment in clinical oncology and is the cause of over 90% of treatment… (more)

▼ Multidrug resistance (MDR) persists to be a major hindrance to the successful treatment in clinical oncology and is the cause of over 90% of treatment failure in cancer. The two main membrane spanning proteins, P-glycoprotein (ABCB1/P-gp) and Multidrug Resistance-associated protein 1 (ABCC1/MRP1) are responsible for the efflux of a plethora of unrelated anti-cancer drugs out of cells, resulting in MDR. Cancer cells overexpressing these efflux proteins are insensitive to chemotherapeutic treatments by maintaining sub-lethal intracellular cytotoxic drug concentrations. Given their enormous substrate profile, of which there is significant overlap, the expression of either efflux protein would result in a poor prognosis. In some cancers, the overexpression of these proteins is correlated with clinical stage, with early stage tumours expressing one efflux transporter and substituted by another transporter at an advanced stage. Our group has established the transfer and dissemination of ABC-transporter mediated MDR via a subset of extracellular vesicles known as microparticles (MPs). This study investigates the molecular mechanisms governing the alteration and acquisition of MDR traits in cancer cell populations via MPs. Spontaneously shed MPs from cancer cells represent a prominent modality for intercellular communication by virtue of their capacity to transport and disseminate bioactive cargo through the vasculature. Their ability to carry large membrane spanning proteins and nucleic acids, imparts their capacity to confer MDR among otherwise drug sensitive tumour cells. Herein, the study validates the MP-transfer and functionality of MRP1 in drug sensitive acute leukaemia cells. The study also introduces MP-mediated trait dominance and demonstrate the re-templating of a pre-existing MDR phenotype in recipient cells. To validate the transfer and translation of MP packaged nucleic acids, a novel methodology was developed, abolishing the requirement for labelled probes and interspecies models. Using, surface peptide shaving, detection of MP packaged P-gp was removed and showed transcript translation of transferred ABCB1 in drug sensitive recipient cells after more than 24 h. Finally, the study identifies transcript suppression mechanisms involved in MP-mediated trait dominance and identify a novel relationship between the function of miRNA with a non-target mRNA transcript. Specifically, the presence of a rival transcript ABCB1 facilitates the ABCC1 suppression by miR-326. These findings substantially advance our understanding on the molecular mechanisms leading to the alteration of MDR traits and can be translated into clinical oncology by providing prognostic information and additional therapeutic targets.

Subjects/Keywords: Multidrug resistance (MDR).; P-glycoprotein (ABCB1/P-gp).; Multidrug Resistance-associated protein 1 (ABCC1/MRP1).; Chemotherapeutic treatments.; ABC-transporter mediated MDR.; Microparticles (MPs).; MP-mediated trait dominance .

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lu, J. F. (2015). Microparticles mediate trait dominance in cancer. (Thesis). University of Technology, Sydney. Retrieved from http://hdl.handle.net/10453/44200

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lu, Jamie Fung. “Microparticles mediate trait dominance in cancer.” 2015. Thesis, University of Technology, Sydney. Accessed April 10, 2021. http://hdl.handle.net/10453/44200.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lu, Jamie Fung. “Microparticles mediate trait dominance in cancer.” 2015. Web. 10 Apr 2021.

Vancouver:

Lu JF. Microparticles mediate trait dominance in cancer. [Internet] [Thesis]. University of Technology, Sydney; 2015. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/10453/44200.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lu JF. Microparticles mediate trait dominance in cancer. [Thesis]. University of Technology, Sydney; 2015. Available from: http://hdl.handle.net/10453/44200

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Clemson University

7. Green, Benjamin. FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION.

Degree: MS, Biological Sciences, 2010, Clemson University

URL: https://tigerprints.clemson.edu/all_theses/893

► The multidrug-resistance associated protein 2 (MRP2) is a membrane-bound transporter responsible for the efflux of a variety of drugs and endogenous compounds. MDCK cells transfected… (more)

Subjects/Keywords: : Multidrug resistance-associated protein 2; fosinopril; methotrexate; Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Green, B. (2010). FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION. (Masters Thesis). Clemson University. Retrieved from https://tigerprints.clemson.edu/all_theses/893

Chicago Manual of Style (16^th Edition):

Green, Benjamin. “FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION.” 2010. Masters Thesis, Clemson University. Accessed April 10, 2021. https://tigerprints.clemson.edu/all_theses/893.

MLA Handbook (7^th Edition):

Green, Benjamin. “FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION.” 2010. Web. 10 Apr 2021.

Vancouver:

Green B. FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION. [Internet] [Masters thesis]. Clemson University; 2010. [cited 2021 Apr 10]. Available from: https://tigerprints.clemson.edu/all_theses/893.

Council of Science Editors:

Green B. FOSINOPRIL, A POTENTIAL SUBSTRATE FOR MRP2, COMPETES WITH SEVERAL HIGH USE PHARMACEUTICALS FOR ELIMINATION. [Masters Thesis]. Clemson University; 2010. Available from: https://tigerprints.clemson.edu/all_theses/893

Queens University

8. Slot, Andrew Johannes. Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates .

Degree: Pathology and Molecular Medicine, 2015, Queens University

URL: http://hdl.handle.net/1974/12748

► The multidrug resistance protein 1 (MRP1) and MRP2 mediate the ATP-dependent cellular efflux of a diverse set of organic molecules including many glutathione (GSH) conjugates.… (more)

▼ The multidrug resistance protein 1 (MRP1) and MRP2 mediate the ATP-dependent cellular efflux of a diverse set of organic molecules including many glutathione (GSH) conjugates. In the present study, a series of GSH conjugated quinones (some of which have been shown to be toxic) were investigated for their ability to interact with human MRP1 and MRP2 using membrane vesicles enriched for these transporters.Several structurally and biologically distinct classes of endogenous (e.g. estradiol) and exogenous (e.g. hydroquinone (HQ),N-methyl-α-methyldopamine (N-Me-α-MeDA), and caffeic acid (CA)) GSH conjugated metabolites inhibited both MRP1- and MRP2-mediated vesicular transport of the prototypic MRPsubstrate (17β-estradiol-17β-D-glucuronide (E217βG)). The relative inhibitory potencies of the metabolites with respect to MRP1 versus MRP2 differed by approximately 10-fold, with the exception of4-hydroxy-2-(glutathion-S-yl)-17β-estradiol (4-OH-2-GS-E2), which differed by 300-fold. The catechol estradiols, N-Me-α-MeDA, and CA metabolites competitively inhibited MRP1-mediated E217βG transport and thus, are potential substrates for this transporter. The estradiol metabolites 2-hydroxy-1-(glutathion-S-yl)-17β-estradiol(2-OH-1-GS-E2) and 4-OH-2-GS-E2were bothsubsequently shown to besubstrates of MRP1 and MRP2by means ofa substrate depletion assay and a vesicular accumulation assay using HPLC with electrochemical detection. Transport of 2-OH-1-GS-E2 by MRP1 was inhibited by several MRP1 substrates (e.g. E217βG, leukotriene C4, and GSH disulfide) and modulators (e.g. MK571 and S-decyl-GSH). The chemically reactiveGSH-conjugated HQ metabolites also inhibited MRP1-mediated vesicular transport of E217βGwith IC50values ranging from 3 – 30 μM. To determine whether these compounds might modify MRP1, MRP1-enriched membrane vesicles were incubated with 2,5-(glutathion-S-yl)-hydroquinone (2,5-GS-HQ) and then immunoblotted with a MRP1-specific monoclonal antibody.An apparentreduction in the electrophoretic mobility of immuno-reactive bands relative to untreated vesicles was observed. However, subsequent limited trypsin digests did not show any differences in the digestion profiles between 2,5-GS-HQ-treated and control vesicles, suggesting no significant differences in protein structure with respect to accessible trypsin cleavage sites. Further experiments are needed to demonstrateMRP1 adduction by 2,5-GS-HQ.In conclusion, the data presented here are the first to show that reactive GSH-conjugated catechol and quinone metabolites can be substrates and modulators of MRP1 and MRP2 in vitro.

Subjects/Keywords: Multidrug Resistance Protein ; Glutathione ; Quinone ; Conjugate

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APA (6^th Edition):

Slot, A. J. (2015). Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/12748

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Slot, Andrew Johannes. “Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates .” 2015. Thesis, Queens University. Accessed April 10, 2021. http://hdl.handle.net/1974/12748.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Slot, Andrew Johannes. “Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates .” 2015. Web. 10 Apr 2021.

Vancouver:

Slot AJ. Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates . [Internet] [Thesis]. Queens University; 2015. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1974/12748.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Slot AJ. Modulation of Human Multidrug Resistance Proteins by Reactive Quinone-based Glutathione Conjugates . [Thesis]. Queens University; 2015. Available from: http://hdl.handle.net/1974/12748

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

NSYSU

9. Hsieh, Li-Chen. Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer.

Degree: Master, Institute of Medical Science and Technology, 2016, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0729116-142939

► Recently, multidrug-resistant (MDR) is one of the major challenges in cancer therapy when the patients have been treated with the chemotherapy. Among potential factors associated… (more)

Subjects/Keywords: Photodynamic therapy; Adeno-associated virus; Multidrug Resistance; Iron oxide nanoparticles; KillerRed

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APA (6^th Edition):

Hsieh, L. (2016). Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0729116-142939

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hsieh, Li-Chen. “Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer.” 2016. Thesis, NSYSU. Accessed April 10, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0729116-142939.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hsieh, Li-Chen. “Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer.” 2016. Web. 10 Apr 2021.

Vancouver:

Hsieh L. Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer. [Internet] [Thesis]. NSYSU; 2016. [cited 2021 Apr 10]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0729116-142939.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hsieh L. Light-triggered Oncolytic Virotherapy Overcome Multidrug Resistance Cancer. [Thesis]. NSYSU; 2016. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0729116-142939

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Kansas

10. Mitra, Pallabi. ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION.

Degree: PhD, Pharmaceutical Chemistry, 2009, University of Kansas

URL: http://hdl.handle.net/1808/6185

► The trophoblast cell layer constitutes the rate-determining barrier for trans-placental transfer. Several isoforms of the sulfotransferase enzymes are functional in placenta but there is only… (more)

▼ The trophoblast cell layer constitutes the rate-determining barrier for trans-placental transfer. Several isoforms of the sulfotransferase enzymes are functional in placenta but there is only limited information available on the utility of cultured trophoblast cells for studying placental sulfation. We examined the expression and activities of four sulfotransferase isoforms (SULT1A1, SULT1A3, SULT1E1, and SULT2A1) in primary cytotrophoblast cells and the trophoblast-like BeWo cell line. These isoforms have been reported to be functional in human placenta. Our results indicated that the phenolic sulfotransferase isoforms, SULT1A1 and SULT1A3, are functional in BeWo, as well as in the primary cytotrophoblast cells. SULT2A1 and SULT1E1 are not functional in either cell type. We also found that chronic exposure to the industrial chemical bisphenol A inhibited SULT1A1 activity. A U-shaped dose-response curve was observed with inhibition (~30-40%) being observed only at intermediate concentrations (10-100 nM). These results suggested that trophoblast cells may be used as a suitable in vitro tool to determine the effect of endogenous or exogenous substances on placental sulfotransferase activity. Altered metabolic activity has the chance of altering fetal exposure to drugs and other substances in the maternal circulation. Studies performed in BeWo cells also suggested that one of the roles of the placental efflux transporters is the elimination of sulfate metabolites. The multidrug resistance-associated proteins (MRPs) played a major role in the elimination of 4-nitrophenyl sulfate and acetaminophen sulfate across the basolateral (fetal-facing) and apical (maternal-facing) trophoblast membranes respectively. The breast cancer resistance protein (BCRP) played a minor role in the elimination of these two sulfate conjugates across the apical membrane. Advisors/Committee Members: Audus, Kenneth L (advisor), Krise, Jeffrey P. (cmtemember), Lunte, Susan M. (cmtemember), Siahaan, Teruna J. (cmtemember), Soares, Michael J (cmtemember).

Subjects/Keywords: Pharmaceutical chemistry; Bisphenol a; Breast cancer resistance protein (bcrp); Multidrug resistance-associated protein (mrp); Placenta; Sulfotransferase enzymes; Trophoblast

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mitra, P. (2009). ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/6185

Chicago Manual of Style (16^th Edition):

Mitra, Pallabi. “ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION.” 2009. Doctoral Dissertation, University of Kansas. Accessed April 10, 2021. http://hdl.handle.net/1808/6185.

MLA Handbook (7^th Edition):

Mitra, Pallabi. “ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION.” 2009. Web. 10 Apr 2021.

Vancouver:

Mitra P. ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION. [Internet] [Doctoral dissertation]. University of Kansas; 2009. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1808/6185.

Council of Science Editors:

Mitra P. ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION. [Doctoral Dissertation]. University of Kansas; 2009. Available from: http://hdl.handle.net/1808/6185

University of Manitoba

11. Wang, Jie. Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection.

Degree: Physiology and Pathophysiology, 2018, University of Manitoba

URL: http://hdl.handle.net/1993/33048

► Background: Doxorubicin is an anti-cancer drug that is widely used in chemotherapy. However, doxorubicin-induced cardiotoxicity is a major risk factor for cancer patients and survivors,… (more)

▼ Background: Doxorubicin is an anti-cancer drug that is widely used in chemotherapy. However, doxorubicin-induced cardiotoxicity is a major risk factor for cancer patients and survivors, and can lead to heart failure. Dexrazoxane is the only approved drug to offer protection against doxorubicin-induced cardiotoxicity, but its use is limited. Strategies are needed to protect the heart against doxorubicin-induced cardiotoxicity and still allow its effective treatment of cancer. Fibroblast growth factors (FGFs) are a family of 23 multifunctional proteins, with properties that include effects on cell growth, survival, efflux transport, and cytoprotection. FGF-16 is the only member of the family that is produced preferentially by postnatal cardiac myocytes. Production of cardiac-specific proteins, including α-actin, troponin I, and myosin light chain 2, are often targeted negatively by doxorubicin due to effects at the transcriptional level. In addition, evidence including from FGF-16 null mice that were stressed through chronic high blood pressure, suggests FGF-16 contributes to the maintenance of a healthy myocardium and may have cardioprotective properties. Hypothesis: FGF-16 synthesis (transcription) is an early target of doxorubicin, and decreased endogenous FGF-16 levels will decrease cardiac myocyte survival and, as a result, may contribute to a decreased resistance to heart damage. Thus, maintaining and/or increasing cardiac FGF-16 levels will increase resistance to doxorubicin-induced cardiotoxicity. This is due, at least in part, to a specific effect on efflux drug transport consistent with a decrease in intracellular doxorubicin concentration in cardiac myocytes. Approaches and Results: Using quantitative polymerase chain reaction, FGF-16 messenger RNA levels were significantly decreased within 6 hours of doxorubicin treatment in both 8-week-old rat hearts and neonatal rat cardiac myocytes. The latter was linked to decreased transcription factor Csx/Nkx2.5 association with the FGF-16 gene promoter, based on the results of transient gene transfer, protein binding, and RNA stability assays. Together with the relatively short FGF-16 mRNA half-life (~1.75 hours), FGF-16 is an early target of doxorubicin-induced cardiotoxicity. Furthermore, a decrease in FGF-16 production using FGF-16 siRNA “knockdown” was linked to reduced cardiac myocyte survival, while an increase in FGF-16 levels using adenoviral delivery was associated with resistance to doxorubicin-induced cardiac dysfunction and cardiac myocyte death; the latter corresponded to an increase in efflux transport of calcein AM and doxorubicin. Discussion: Observations made demonstrate that postnatal cardiac-specific FGF-16 synthesis is an early target of acute doxorubicin-induced cardiotoxicity due to a negative effect on the cardiac transcription factor Csx/Nkx2.5 and the relatively unstable FGF-16 transcripts. Endogenous FGF-16 helps maintain neonatal cardiac myocyte viability, while exogenous FGF-16 is protective by, at least in part, upregulation of… Advisors/Committee Members: Cattini, Peter A. (Physiology and Pathophysiology) (supervisor), Czubryt, Michael (Physiology and Pathophysiology) Nachtigal, Mark (Biochemistry and Medical Genetics) Kardami, Elissavet (Human Anatomy and Cell Science) Fernig, David (University of Liverpool) (examiningcommittee).

Subjects/Keywords: Fibroblast growth factor 16; doxorubicin; multidrug resistance protein 1; cardioprotection

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APA (6^th Edition):

Wang, J. (2018). Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/33048

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Jie. “Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection.” 2018. Thesis, University of Manitoba. Accessed April 10, 2021. http://hdl.handle.net/1993/33048.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Jie. “Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection.” 2018. Web. 10 Apr 2021.

Vancouver:

Wang J. Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection. [Internet] [Thesis]. University of Manitoba; 2018. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1993/33048.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang J. Fibroblast growth factor-16 and acute doxorubicin cardiotoxicity: a target for early protection. [Thesis]. University of Manitoba; 2018. Available from: http://hdl.handle.net/1993/33048

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University

12. Wang, Xiaoqian. Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) .

Degree: Pathology and Molecular Medicine, 2008, Queens University

URL: http://hdl.handle.net/1974/1610

► Multidrug resistance protein 1 (MRP1) is an integral membrane protein belonging to the ATP-binding cassette (ABC) superfamily that utilizes ATP binding and hydrolysis to transport… (more)

▼ Multidrug resistance protein 1 (MRP1) is an integral membrane protein belonging to the ATP-binding cassette (ABC) superfamily that utilizes ATP binding and hydrolysis to transport various endogenous substrates and/or xenobiotics across membranes against a concentration gradient. The overall goal of my research was to examine the nucleotide and protein interactions of MRP1 using various biochemical methods. In the first study, Cu2+(Ph)3 which promotes cross-linking of two nearby Cys residues and limited proteolysis were used to study conformational changes of MRP1 at different stages of ATP binding and hydrolysis at the nucleotide binding domains (NBDs). The limited trypsin digestion patterns indicated that some Cys residues of MRP1 could be cross-linked in the nucleotide-free state and that the Cys cross-linked MRP1 was more susceptible to trypsinolysis. Furthermore, binding of ATP, AMP-PNP, and trapping of ADP by MRP1 prevented the cross-linking events from occurring, but binding of ATPγS did not. However, the ATPγS-bound MRP1, like nucleotide-free MRP1, showed enhanced sensitivity towards trypsinolysis. These studies show that the two ATP analogs, AMP-PNP and ATPγS, interact with MRP1 in different ways. In the second study, the interaction of MRP1 with other cellular proteins was examined. An in vivo chemical cross-linking approach combined with affinity purification and MS analysis was initially used to identify protein partners directly interacting with MRP1. When this approach proved unsuccessful, a second approach involving immunoaffinity purification of MRP1-containing complexes followed by MS analysis was adopted. Six potential candidate interacting protein partners of MRP1 were identified via this approach and two of them, FUS and drebrin, were further characterized by co-immunoprecipitation and colocalization experiments. FUS seems unlikely to be an important binding partner of MRP1 since confocal and subcellular fractionation studies showed it to be exclusively localized in the nucleus. On the other hand, drebrin depletion by siRNA knock-down resulted in a moderate decrease in MRP1 overall expression levels although the membrane localization of MRP1 remained unchanged.

Subjects/Keywords: protein interaction ; multidrug resistance

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APA (6^th Edition):

Wang, X. (2008). Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/1610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Xiaoqian. “Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) .” 2008. Thesis, Queens University. Accessed April 10, 2021. http://hdl.handle.net/1974/1610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Xiaoqian. “Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) .” 2008. Web. 10 Apr 2021.

Vancouver:

Wang X. Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) . [Internet] [Thesis]. Queens University; 2008. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1974/1610.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang X. Biochemical Characterization of Nucleotide and Protein Interactions of Human Multidrug Resistance Protein 1 (MRP1/ABCC1) . [Thesis]. Queens University; 2008. Available from: http://hdl.handle.net/1974/1610

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ottawa

13. Rainey, Jenna. The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta .

Degree: 2011, University of Ottawa

URL: http://hdl.handle.net/10393/19961

► Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety… (more)

Subjects/Keywords: Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp); Breast Cancer Resistance Protein (BCRP); Human Placenta

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APA (6^th Edition):

Rainey, J. (2011). The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/19961

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rainey, Jenna. “The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta .” 2011. Thesis, University of Ottawa. Accessed April 10, 2021. http://hdl.handle.net/10393/19961.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rainey, Jenna. “The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta .” 2011. Web. 10 Apr 2021.

Vancouver:

Rainey J. The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta . [Internet] [Thesis]. University of Ottawa; 2011. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/10393/19961.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rainey J. The Regulation of Multidrug Resistance Phosphoglycoprotein (MDR1/P-gp) and Breast Cancer Resistance Protein (BCRP) in the Human Placenta . [Thesis]. University of Ottawa; 2011. Available from: http://hdl.handle.net/10393/19961

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

14. 渡辺, 喬之. Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構.

Degree: 博士(医薬学), 2013, Chiba University / 千葉大学

URL: http://opac.ll.chiba-u.jp/da/curator/900118747/

研究科: 千葉大学大学院医学薬学府

学位:千大院医薬博甲第医薬58号

Advisors/Committee Members: 千葉大学大学院医学薬学府.

Subjects/Keywords: arsenic; toxicity; metabolism; multidrug-resistance associated protein; ヒ素; 毒性; 代謝; 多剤耐性タンパク

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APA (6^th Edition):

渡辺, �. (2013). Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構. (Thesis). Chiba University / 千葉大学. Retrieved from http://opac.ll.chiba-u.jp/da/curator/900118747/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

渡辺, 喬之. “Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構.” 2013. Thesis, Chiba University / 千葉大学. Accessed April 10, 2021. http://opac.ll.chiba-u.jp/da/curator/900118747/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

渡辺, 喬之. “Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構.” 2013. Web. 10 Apr 2021.

Vancouver:

渡辺 �. Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構. [Internet] [Thesis]. Chiba University / 千葉大学; 2013. [cited 2021 Apr 10]. Available from: http://opac.ll.chiba-u.jp/da/curator/900118747/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

渡辺 �. Modulatiion of arsenic toxicity via MRPs in cells : 多剤耐性タンパクMRPsを介した細胞のヒ素毒性調節機構. [Thesis]. Chiba University / 千葉大学; 2013. Available from: http://opac.ll.chiba-u.jp/da/curator/900118747/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

15. Park, Han-A. Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant.

Degree: PhD, Human Ecology: Human Nutrition, 2010, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291061955

► Natural vitamin E exists as the well known tocopherols and poorly studied tocotrienols. α-Tocotrienol (TCT) represents the most potent neuroprotective form of vitamin E.… (more)

▼ Natural vitamin E exists as the well known tocopherols and poorly studied tocotrienols. α-Tocotrienol (TCT) represents the most potent neuroprotective form of vitamin E. This work addresses a novel molecular mechanism by which α-TCT may be protective against stroke. Reduced glutathione (GSH) is a low molecular weight intracellular thiol in all aerobic cells. Under conditions of oxidative stress such as during stroke, large amounts of GSH are rapidly oxidized to glutathione disulfide (GSSG). The current study demonstrates that elevation of intracellular GSSG concentration may trigger neural cell death via a 12-lipoxygenase (12-Lox) dependent mechanism. Furthermore, this work elucidates that α-TCT may improve GSSG clearance in cells subjected to oxidative stress via upregulaton of multidrug resistance-associated protein 1 (MRP1) in the stroke-affected brain. Objective: This dissertation addresses three specific aims: (i) determine the role of intracellular GSSG in neural cell death; (ii) characterize the significance of MRP1 as a GSSG efflux pathway in experimental stroke; and (iii) determine the MRP1-dependent neuroprotective property of α-TCT against stroke Experimental approach and results: To elucidate the specific significance of GSSG in neural cell death, intracellular GSSG was specifically elevated by single cell microinjection. Control HT4 neural cells were microinjected with either the corresponding reduced form GSH or the vehicle (PBS). GSSG, but not GSH, caused cell death at pathophysiologically relevant concentrations. GSSG-induced death of the neural cells was protected in the presence of 12-Lox inhibitor or α-TCT. GSSG-dependent glutathionylation of 12-Lox emerged a critical player in neural cell death. Next, to test whether impaired cellular clearance of GSSG aggravates stroke-induced brain injury in vivo, middle cerebral artery occlusion (MCAO) was performed in MRP1-/- mice. Larger stroke-induced lesion in MRP-/- mice recognized a protective role of MRP1. In vitro, protection against glutamate-induced neurotoxicity by α-TCT was attenuated under conditions of MRP1 knockdown suggesting a role of MRP1 in α-TCT-dependent neuroprotection. In vivo studies demonstrated that oral supplementation of α-TCT protected brain against stroke-induced injury. MRP1 expression was elevated in the stroke affected tissue of α-TCT-supplemented mice. Efforts to elucidate the underlying mechanism identified MRP1 as a target of miR-199a-5p. In α-TCT supplemented mice, miR-199a-5p was downregulated in the stroke-affected tissue. This work recognizes MRP1 as a protective factor against stroke. Conclusions: Work in this dissertation adds a new dimension to the current understanding of the molecular bases of α-TCT neuroprotection by identifying MRP1 as a α-TCT-sensitive target and by unveiling the general prospect that oral α-TCT may regulate microRNA expression in stroke-affected brain tissue. Advisors/Committee Members: Sen, Chandan (Advisor).

Subjects/Keywords: Molecular Biology; Neurobiology; Nutrition; &945; -tocotrienol; glutathione disulfide; multidrug resistance-associated protein 1; stroke; 12-lipoxygenase

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APA (6^th Edition):

Park, H. (2010). Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1291061955

Chicago Manual of Style (16^th Edition):

Park, Han-A. “Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant.” 2010. Doctoral Dissertation, The Ohio State University. Accessed April 10, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1291061955.

MLA Handbook (7^th Edition):

Park, Han-A. “Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant.” 2010. Web. 10 Apr 2021.

Vancouver:

Park H. Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant. [Internet] [Doctoral dissertation]. The Ohio State University; 2010. [cited 2021 Apr 10]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291061955.

Council of Science Editors:

Park H. Natural Vitamin E, α-Tocotrienol, as a Neuroprotectant. [Doctoral Dissertation]. The Ohio State University; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291061955

University of Kentucky

16. Ye, Cui. STABILITY STUDIES OF MEMBRANE PROTEINS.

Degree: 2014, University of Kentucky

URL: https://uknowledge.uky.edu/chemistry_etds/33

► The World Health Organization has identified antimicrobial resistance as one of the top three threats to human health. Gram-negative bacteria such as Escherichia coli are… (more)

▼ The World Health Organization has identified antimicrobial resistance as one of the top three threats to human health. Gram-negative bacteria such as Escherichia coli are intrinsically more resistant to antimicrobials. There are very few drugs either on the market or in the pharmaceutical pipeline targeting Gram-negative pathogens. Two mechanisms, the protection of the outer membrane and the active efflux by the multidrug transporters, play important roles in conferring multidrug resistance to Gram-negative bacteria. My work focuses on two main directions, each aligning with one of the known multidrug resistance mechanisms. The first direction of my research is in the area of the biogenesis of the bacterial outer membrane. The outer membrane serves as a permeability barrier in Gram-negative bacteria. Antibiotics cross the membrane barrier mainly via diffusion into the lipid bilayer or channels formed by outer membrane proteins. Therefore, bacterial drug resistance is closely correlated with the integrity of the outer membrane, which depends on the correct folding of the outer membrane proteins. The folding of the outer membrane proteins has been studied extensively in dilute buffer solution. However, the cell periplasm, where the folding actually occurs, is a crowded environment. In Chapter 2, effects of the macromolecular crowding on the folding mechanisms of two bacterial outer membrane proteins (OmpA and OmpT) were examined. Our results suggested that the periplasmic domain of OmpA improved the efficiency of the OmpA maturation under the crowding condition, while refolding of OmpT was barely affected by the crowding. The second direction of my research focuses on the major multidrug efflux transporter in Gram-negative bacteria, AcrB. AcrB is an obligate trimer, which exists and functions exclusively in a trimeric state. In Chapter 3, the unfolding of the AcrB trimer was investigated. Our results revealed that sodium dodecyl sulfate induced unfolding of the trimeric AcrB started with a local structural rearrangement. While the refolding of secondary structure in individual monomers could be achieved, the re-association of the trimer might be the limiting factor to obtain folded wild type AcrB. In Chapter 4, the correlation between the AcrB trimer stability and the transporter activity was studied. A non-linear correlation was observed, in which the threshold trimer stability was required to maintain the efflux activity. Finally, in Chapter 5, the stability of another inner membrane protein, AqpZ, was studied. AqpZ was remarkably stable. Several molecular engineering approaches were tested to improve the thermal stability of the protein.

Subjects/Keywords: Multidrug resistance; multidrug efflux pump; outer membrane proteins; protein stability; AcrB; Biochemistry; Molecular Biology; Structural Biology

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APA (6^th Edition):

Ye, C. (2014). STABILITY STUDIES OF MEMBRANE PROTEINS. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/chemistry_etds/33

Chicago Manual of Style (16^th Edition):

Ye, Cui. “STABILITY STUDIES OF MEMBRANE PROTEINS.” 2014. Doctoral Dissertation, University of Kentucky. Accessed April 10, 2021. https://uknowledge.uky.edu/chemistry_etds/33.

MLA Handbook (7^th Edition):

Ye, Cui. “STABILITY STUDIES OF MEMBRANE PROTEINS.” 2014. Web. 10 Apr 2021.

Vancouver:

Ye C. STABILITY STUDIES OF MEMBRANE PROTEINS. [Internet] [Doctoral dissertation]. University of Kentucky; 2014. [cited 2021 Apr 10]. Available from: https://uknowledge.uky.edu/chemistry_etds/33.

Council of Science Editors:

Ye C. STABILITY STUDIES OF MEMBRANE PROTEINS. [Doctoral Dissertation]. University of Kentucky; 2014. Available from: https://uknowledge.uky.edu/chemistry_etds/33

Rutgers University

17. Udasin, Ronald G., 1987-. Resistance to vesicant injury by efflux transporters.

Degree: PhD, Toxicology, 2015, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48705/

►

Sulfur mustard and nitrogen mustard (mechlorethamine, HN2) are potent vesicants used in chemical warfare and cancer chemotherapy that primarily target skin, eye, and lung. These… (more)

▼

Sulfur mustard and nitrogen mustard (mechlorethamine, HN2) are potent vesicants used in chemical warfare and cancer chemotherapy that primarily target skin, eye, and lung. These electrophilic, bifunctional alkylating agents cause oxidative stress and persistent tissue damage. Toxicity of related mustards, chlorambucil and melphalan, is limited by clearance from cells by multidrug resistance-associated protein 1 (MRP1/Mrp1), a transmembrane ATPase that stimulates efflux of glutathione-conjugated electrophiles. HN2 causes injury by covalently modifying biomolecules including glutathione. Monofunctional glutathione adducts contribute to cytotoxicity or are exported by MRP1/Mrp1. In A549 lung epithelial cells, which express MRP1 and MRP2, HN2 inhibits growth (IC5o = 0.18 µM), and inhibition of MRPs by MK-571 increases sensitivity to HN2 (IC50 = 0.045 µM). Similar effects are seen for other bifunctional mustards chlorambucil and melphalan. Using human embryonic kidney (HEK) 293 cells overexpressing MRP1 and MRP2, we determined that MRP1 provides resistance to HN2 while MRP2 does not protect the cells. HN2 inhibited MRP functional activity in both A549 cells and HEK cells overexpressing MRP1, and increased sensitivity to growth inhibition induced by MRP1/Mrp1 substrates etoposide, methotrexate, and vincristine in A549 cells. PAM212 cells and primary mouse keratinocytes express Mrp1 mRNA and protein. Activation of the transcription factor Nrf2 by sulforaphane increased Mrp1 mRNA, protein expression and activity in PAM212 cells and protected cells against HN2-induced growth inhibition (IC50 = 1 and 13 µM without and with sulforaphane, respectively). This protection was reversed by MK-571 (IC50 = 0.63 µM). Sulforaphane increased Mrp1 mRNA and protein expression and activity and decreased HN2 growth inhibition in primary keratinocytes (IC50 = 1.4 and 4.8 µM without and with sulforaphane, respectively). This attenuation was reversed by MK-571 (IC50 = 0.27 µM). MK-571 increases HN2-induced cytotoxicity in primary mouse keratinocytes (growth inhibition IC50 = 1.4 and 0.48 µM, without and with MK-571, respectively). Sulforaphane did not protect keratinocytes from Nrf2-/- mice (IC50 = 0.31 and 0.14 µM without and with sulforaphane, respectively). These data show MRP1/Mrp1-mediated efflux is important for regulating HN2 injury. Inhibiting MRP1/Mrp1 may increase mustard efficacy in cancer chemotherapy, while enhancing transport may represent a promising route to mitigate vesicant-induced cytotoxicity.

Advisors/Committee Members: Guo, Grace (chair), Laskin, Jeffrey D (internal member), Aleksunes, Lauren M (internal member), Gallo, Michael A (internal member), Gordon, Marion (internal member), Heindel, Ned D (outside member).

Subjects/Keywords: Multidrug resistance; Chemotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Udasin, Ronald G., 1. (2015). Resistance to vesicant injury by efflux transporters. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48705/

Chicago Manual of Style (16^th Edition):

Udasin, Ronald G., 1987-. “Resistance to vesicant injury by efflux transporters.” 2015. Doctoral Dissertation, Rutgers University. Accessed April 10, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/48705/.

MLA Handbook (7^th Edition):

Udasin, Ronald G., 1987-. “Resistance to vesicant injury by efflux transporters.” 2015. Web. 10 Apr 2021.

Vancouver:

Udasin, Ronald G. 1. Resistance to vesicant injury by efflux transporters. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Apr 10]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48705/.

Council of Science Editors:

Udasin, Ronald G. 1. Resistance to vesicant injury by efflux transporters. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48705/

University of Toronto

18. Tan, Kah Poh. Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities.

Degree: 2008, University of Toronto

URL: http://hdl.handle.net/1807/17287

►

Exposure to toxic bile acids (BA) and retinoic acids (RA) is implicated in toxicities related to excessive oxidative stress. This thesis examined roles and mechanisms… (more)

▼

Exposure to toxic bile acids (BA) and retinoic acids (RA) is implicated in toxicities related to excessive oxidative stress. This thesis examined roles and mechanisms of the oxidative stress-responsive nuclear factor (erythroid 2-like) factor 2 (Nrf2) in adaptive cell defense against BA and RA toxicities. Using liver cells and mouse models, many antioxidant proteins known to be Nrf2 target genes, particularly the rate-limiting enzyme for glutathione (GSH) biosynthesis, i.e., glutamate-cysteine ligase subunits (GCLM/GCLC), were induced by BA [lithocholic acid (LCA)] or RA (all-trans, 9-cis and 13-cis) treatment. Evidence for increased Nrf2 transactivation by LCA and all-trans-RA was exemplified in HepG2 by: (1) reduced constitutive and inducible expression of GCLM/GCLC upon Nrf2 silencing via small-interfering RNA; (2) increased inducible expression of GCLM/GCLC genes by Nrf2 overexpression, but overexpression of dominant-negative Nrf2 decreased it; (3) increased nuclear accumulation of Nrf2 as signature event of receptor activation; (4) enhanced Nrf2-dependent antioxidant-response-element (ARE) reporter activity as indicative of increased Nrf2 transactivation; and (5) increased Nrf2 occupancy to AREs of GCLM and GCLC. Additionally, in BA-treated HepG2 cells, we observed concomitant increases of many ATP-binding cassette (ABC) transporters (MRPs 1-5, MDR1 and BCRP) in parallel with increased cellular efflux. Nrf2 silencing in HepG2 cells decreased constitutive and inducible expression of MRP2, MRP3 and ABCG2. However, Nrf2-silenced mouse hepatoma cells, Hepa1c1c7, and Nrf2-/- mice had decreased constitutive and/or inducible expression of Mrps 1-4, suggesting species differences in Nrf2-dependent regulation of hepatic ABC transporters. Protection by Nrf2 against BA and RA toxicities was confirmed by observations that Nrf2 silencing increased cell susceptibility to BA- and RA-induced cell death. Moreover, Nrf2-/- mice suffered more severe liver injury than the wildtype. Increased GSH and efflux activity following increased GCLM/GCLC and ABC transporters, respectively, can mitigate LCA toxicity. Activation of MEK1-ERK1/2 MAPK was shown to primarily mediate Nrf2 transactivation and LCA-induced expression of antioxidant proteins and Nrf2-dependent and -independent ABC transporters. In conclusion, Nrf2 activation by BA and RA led to coordinated induction of antioxidant and ABC proteins, thereby counteracting resultant oxidative cytotoxicity. The potential of targeting Nrf2 in management of BA and RA toxicities merits further investigation.

PhD

Advisors/Committee Members: Ito, Shinya, Pharmacology.

Subjects/Keywords: oxidative stress; glutathione; bile acid; Nrf2; retinoic acid; cholestasis; ATP-binding cassette transporters; mitogen activated protein kinase; multidrug resistance associated proteins; adaptive response; antioxidants; thioredoxin reductase; 4-hydroxynonenal; lipid peroxidation; glutathione S-transferase; liver toxicity; antioxidant response element; cell defense; 0383

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tan, K. P. (2008). Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/17287

Chicago Manual of Style (16^th Edition):

Tan, Kah Poh. “Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities.” 2008. Doctoral Dissertation, University of Toronto. Accessed April 10, 2021. http://hdl.handle.net/1807/17287.

MLA Handbook (7^th Edition):

Tan, Kah Poh. “Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities.” 2008. Web. 10 Apr 2021.

Vancouver:

Tan KP. Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities. [Internet] [Doctoral dissertation]. University of Toronto; 2008. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1807/17287.

Council of Science Editors:

Tan KP. Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities. [Doctoral Dissertation]. University of Toronto; 2008. Available from: http://hdl.handle.net/1807/17287

University of Tennessee – Knoxville

19. Samuels, Ronita. An Epidemiologic Study of Antimicrobial Resistance.

Degree: 2019, University of Tennessee – Knoxville

URL: https://trace.tennessee.edu/utk_graddiss/5703

► The emergence of antimicrobial resistant bacteria has become a serious public health concern. The use of antimicrobials for prophylaxis make it important to estimate the… (more)

▼ The emergence of antimicrobial resistant bacteria has become a serious public health concern. The use of antimicrobials for prophylaxis make it important to estimate the magnitude of the problem in the animal population. The aim of the second chapter in this study is to investigate the burden and patterns of antimicrobial resistance (AMR) among equine Staphylococcus samples submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) from 1993 to 2009. The proportion of resistant isolates by animal breed, species of organism, sample source, and time period were computed. Chi-square and Cochran-Armitage trend tests were used to identify significant associations and temporal trends, respectively. Logistic regression models were used to investigate predictors of AMR and multidrug resistance (MDR).In addition to the problem of antimicrobial resistant bacteria, appropriate usage of antimicrobials is also a global public health concern where opinions regarding appropriate use vary greatly amongst veterinarians. Therefore, the objectives of the third chapter of this study are to investigate the opinions, knowledge and perceptions of veterinarians in Kentucky regarding AMR and antimicrobial prescription practices as well as to identify predictors of their knowledge and opinions. This cross-sectional study uses a 30-question survey questionnaire administered to members of the Kentucky Veterinary Medical Association (KVMA). The proportion of responses to survey questions and 95% confidence intervals were computed. Predictors of improper use of antimicrobials and antimicrobial prescription practices of the respondents as well as their colleagues were investigated using multinomial logistic regression models.The appropriate usage of antimicrobials is also an important topic in developing countries such as South Africa. Thus, the fourth chapter in this study investigates the knowledge, prescription practices and attitudes towards AMR among veterinarians in the City of Tshwane, Metropolitan Municipality. A 30-question survey was administered and the percentages of responses to survey questions and their 95% confidence intervals will be computed. Ordinary logistic models are used to investigate predictors of knowledge of antimicrobial resistance and antimicrobial prescription practices of respondents. Predictors of antimicrobial prescription practices of respondents’ colleagues are identified using multinomial logistic models.

Subjects/Keywords: Antimicrobial Resistance; multidrug resistance; Staphylococcus

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APA (6^th Edition):

Samuels, R. (2019). An Epidemiologic Study of Antimicrobial Resistance. (Doctoral Dissertation). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_graddiss/5703

Chicago Manual of Style (16^th Edition):

Samuels, Ronita. “An Epidemiologic Study of Antimicrobial Resistance.” 2019. Doctoral Dissertation, University of Tennessee – Knoxville. Accessed April 10, 2021. https://trace.tennessee.edu/utk_graddiss/5703.

MLA Handbook (7^th Edition):

Samuels, Ronita. “An Epidemiologic Study of Antimicrobial Resistance.” 2019. Web. 10 Apr 2021.

Vancouver:

Samuels R. An Epidemiologic Study of Antimicrobial Resistance. [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2019. [cited 2021 Apr 10]. Available from: https://trace.tennessee.edu/utk_graddiss/5703.

Council of Science Editors:

Samuels R. An Epidemiologic Study of Antimicrobial Resistance. [Doctoral Dissertation]. University of Tennessee – Knoxville; 2019. Available from: https://trace.tennessee.edu/utk_graddiss/5703

20. Delmar, Jared Armand. A structural biology approach to the problem of antibiotic resistance in bacteria.

Degree: 2017, Iowa State University

URL: https://lib.dr.iastate.edu/etd/15291

► X-ray crystallography remains the most robust method to determine protein structure at the atomic level. We demonstrate how these structural studies can directly contribute to… (more)

▼ X-ray crystallography remains the most robust method to determine protein structure at the atomic level. We demonstrate how these structural studies can directly contribute to unsolved problems in biology, with a focus on the growing problem of antibiotic resistance in bacterial infections. Multi-drug efflux transporters are common and powerful resistance mechanisms that are capable of extruding a number of structurally unrelated antimicrobials, including antibiotics and toxic heavy metal ions, from the bacterial cell. We begin by presenting the crystal structures of the individual pump components of the Escherichia coli Cus system, a paradigm for efflux machinery, and speculate on how these pumps assemble to fight diverse antimicrobials. In Mycobacterium tuberculosis, the cell wall is critical to the virulence and antimicrobial resistance of these pathogens. Recent work shows that the MmpL transporter family contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the M. tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. We demonstrate how the structures of these two proteins enhance understanding of the MmpL family of proteins and to develop new antibacterial tools to fight tuberculosis. Neisseria gonorrhoeae is a Gram-negative human pathogen and the cause of the STD gonorrhea. In N. gonorrhoeae, the MtrCDE multidrug efflux system mediates resistance to diverse antibiotics, nonionic detergents, antibacterial peptides, bile salts, and steroidal hormones. We have developed several techniques to assemble the complete MtrCDE tripartite efflux complex, which we present here. These efforts have culminated in a low-resolution structure of the bipartite MtrCD complex. Finally, we apply our crystallography techniques to the problem of chloroplast cell division. In plants and algae, chloroplast division proceeds by binary fission, involving the coordinated assembly of four rings, both inside and outside the cell. We have determined the first high-resolution crystal structure of the Arabidopsis thaliana cell division protein PARC6. In addition, we obtained the co-crystal structure of PARC6 and PDV1, another protein within this network, revealing the molecular details of the intermembrane space interaction during chloroplast cell division.

Subjects/Keywords: Antimicrobial efflux; Chloroplast cell division; Membrane protein crystallization; Multidrug resistance; Xray crystallography; Biochemistry; Molecular Biology

12 more images…

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APA (6^th Edition):

Delmar, J. A. (2017). A structural biology approach to the problem of antibiotic resistance in bacteria. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/15291

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Delmar, Jared Armand. “A structural biology approach to the problem of antibiotic resistance in bacteria.” 2017. Thesis, Iowa State University. Accessed April 10, 2021. https://lib.dr.iastate.edu/etd/15291.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Delmar, Jared Armand. “A structural biology approach to the problem of antibiotic resistance in bacteria.” 2017. Web. 10 Apr 2021.

Vancouver:

Delmar JA. A structural biology approach to the problem of antibiotic resistance in bacteria. [Internet] [Thesis]. Iowa State University; 2017. [cited 2021 Apr 10]. Available from: https://lib.dr.iastate.edu/etd/15291.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Delmar JA. A structural biology approach to the problem of antibiotic resistance in bacteria. [Thesis]. Iowa State University; 2017. Available from: https://lib.dr.iastate.edu/etd/15291

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Tampere University

21. Haukipää, Mia. Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa .

Degree: 2014, Tampere University

URL: https://trepo.tuni.fi/handle/10024/96116

► Sarveiskalvon epiteelin on opittu ilmentävän efflux-proteiineja MRP1-6 (multiresistance protein 1-6), P-gp (P-glykoproteiini) ja BCRP (breast cancer resistance protein), jotka pumppaavat substraattejaan ulos solusta. Tämän tiedon… (more)

Subjects/Keywords: sarveiskalvon epiteeli; hiPSC; HCE; efflux-kuljettajaproteiini; multidrug resistance protein; P-glykoproteiini; breast cancer related proteiini

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Haukipää, M. (2014). Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa . (Masters Thesis). Tampere University. Retrieved from https://trepo.tuni.fi/handle/10024/96116

Chicago Manual of Style (16^th Edition):

Haukipää, Mia. “Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa .” 2014. Masters Thesis, Tampere University. Accessed April 10, 2021. https://trepo.tuni.fi/handle/10024/96116.

MLA Handbook (7^th Edition):

Haukipää, Mia. “Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa .” 2014. Web. 10 Apr 2021.

Vancouver:

Haukipää M. Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa . [Internet] [Masters thesis]. Tampere University; 2014. [cited 2021 Apr 10]. Available from: https://trepo.tuni.fi/handle/10024/96116.

Council of Science Editors:

Haukipää M. Efflux-geenien ilmentyminen hiPS-soluista erilaistetuissa sarveiskalvon epiteelisoluissa . [Masters Thesis]. Tampere University; 2014. Available from: https://trepo.tuni.fi/handle/10024/96116

Universiteit Utrecht

22. Lagas, J.S. Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice.

Degree: 2009, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/34065

► ATP-binding cassette (ABC) multidrug transporters are drug efflux pumps located in the plasma membrane that utilize the energy of ATP hydrolysis to extrude a wide… (more)

▼ ATP-binding cassette (ABC) multidrug transporters are drug efflux pumps located in the plasma membrane that utilize the energy of ATP hydrolysis to extrude a wide spectrum of endogenous and exogenous compounds from cells, including numerous (anticancer) drugs and/or their metabolites. The studies described in this thesis focus on the pharmacological functions of the ABC transporters: P-glycoprotein (P-gp/ABCB1), the Multidrug Resistance Proteins 2 and 3 (MRP2/ABCC2 and MRP3/ABCC3) and the Breast Cancer Resistance Protein (BCRP/ABCG2). Most results presented in this thesis were obtained by studying single and combination ABC multidrug transporter knockout mice. As ABC multidrug transporters do not only have very broad, but also substantially overlapping substrate specificities, they can often partially, or sometimes even fully, compensate for the loss of each other. Combination ABC drug transporter knockout mice are therefore invaluable tools to study the separate roles and functional overlap of ABC multidrug transporters. We generated and characterized combination P-gp/Mrp2 knockout mice and used these to assess the distinct roles of P-gp and Mrp2 in the pharmacokinetics of the anticancer drug paclitaxel. Although paclitaxel is an excellent P-gp substrate, Mrp2 was found to almost exclusively mediate the excretion of paclitaxel from the liver into the bile, whereas P-gp had little effect. This finding is especially interesting because Mrp2 was thus far thought to mainly affect organic anionic drugs in vivo. However, we show that Mrp2 can also be a major determinant of the pharmacokinetic behavior of highly lipophilic anti-cancer drugs, even in the presence of other efficient transporters. P-gp and BCRP combination knockout mice enabled us to demonstrate that both multidrug transporters act in concert at the blood-brain barrier in restricting the brain penetration of the novel tyrosine kinase inhibitor anticancer drugs dasatinib and sorafenib. Brain penetration of dasatinib was primarily restricted by P-gp, whereas loss of BCRP had no effect. However, when both transporters were absent a disproportionate increase in brain penetration of dasatinib was observed. In contrast, for sorafenib it was the other way around, i.e. absence of P-gp had no effect while BCRP deficiency resulted in markedly elevated brain levels. Again, simultaneous loss of both transporters resulted in a highly increased brain penetration. When we combined dasatinib with the dual P-gp and BCRP inhibitor elacridar we found that the brain penetration in wild-type mice could be increased to P-gp/BCRP knockout levels. These findings might be clinically relevant for patients with intracranial tumors, as concomitant administration of an inhibitor of P-gp and ABCG2 with dasatinib, sorafenib and possibly other tyrosine kinase inhibitors might result in better therapeutic responses in these patients. In conclusion, the studies described in this thesis demonstrate the power of combination ABC multidrug transporter knockout mouse models to study the… Advisors/Committee Members: Beijnen, J.H., Schinkel, J.M..

Subjects/Keywords: Farmacie; ATP-binding cassette (ABC); ABC multidrug transporter; ABC transporter knockout mice; Combination transporter knockout mice; P-glycoprotein; Multidrug Resistance Protein 2; Breast Cancer Resistance Protein; Multidrug Resistance; Pharmacokinetics; Blood-brain barrier

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lagas, J. S. (2009). Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/34065

Chicago Manual of Style (16^th Edition):

Lagas, J S. “Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice.” 2009. Doctoral Dissertation, Universiteit Utrecht. Accessed April 10, 2021. http://dspace.library.uu.nl:8080/handle/1874/34065.

MLA Handbook (7^th Edition):

Lagas, J S. “Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice.” 2009. Web. 10 Apr 2021.

Vancouver:

Lagas JS. Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2009. [cited 2021 Apr 10]. Available from: http://dspace.library.uu.nl:8080/handle/1874/34065.

Council of Science Editors:

Lagas JS. Pharmacological functions of multidrug transporters: studies employing combination transporter knockout mice. [Doctoral Dissertation]. Universiteit Utrecht; 2009. Available from: http://dspace.library.uu.nl:8080/handle/1874/34065

23. Verchère, Alice. Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa.

Degree: Docteur es, Biochimie et biologie moléculaire, 2014, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2014PA05P622

►

L’efflux actif, qui permet aux bactéries d’exporter les antibiotiques vers le milieu extérieur est l’un des mécanismes majeurs de résistance aux antibiotiques. L’une des pompes… (more)

▼

L’efflux actif, qui permet aux bactéries d’exporter les antibiotiques vers le milieu extérieur est l’un des mécanismes majeurs de résistance aux antibiotiques. L’une des pompes d’efflux de Pseudomonas aeruginosa, MexA-MexB-OprM, est constituée de trois protéines : i) MexA, une protéine membranaire de fusion qui se trouve dans le périplasme ; ii) MexB qui se trouve dans la membrane interne et qui reconnaît l’antibiotique et initie son transport grâce à la force protomotrice et iii) OprM un canal qui se trouve dans la membrane externe. Durant ma thèse, j’ai mis au point un test fonctionnel pour MexA et MexB. Ce test est basé sur la coreconstitution de ces protéines avec la bactériorhodopsine, une protéine membranaire qui génère un gradient de proton après activation par la lumière. L’activité de MexB est suivie de manière indirecte via la mesure du pH. En mesurant le pH à l’intérieur des liposomes, on peut connaître l’activité de MexB puisque ce dernier utilise la force protomotrice pour transporter ses substrats. Une mesure fiable du pH peut être obtenue grâce à la pyranine dont la fluorescence varie avec le pH. Grâce à ce test, j’ai prouvé que MexB possède une activité basale qui ne dépend pas de la présence de substrat et que l’activité de MexB devient optimale quand cette dernière est reconstituée en présence de MexA. Dans un deuxième temps, j’ai mis au point un test fonctionnel pour la pompe d’efflux entière. Pour cela, je prépare deux types distincts de protéoliposomes. Dans le premier type de liposome, j’encapsule de la pyranine, (pour suivre l’activité de MexB) et un substrat de MexB qui est un agent intercalant de l’ARN. Ce substrat est faiblement fluorescent dans un environnement aqueux et fortement fluorescent lorsqu’il est intercalé dans l'ARN. MexB et MexA sont reconstitués dans ces liposomes. Dans le deuxième type de liposomes, je reconstitue OprM et j’encapsule de l’ARN. Ces deux types de liposomes sont alors mélangés. Lorsque la pompe s’assemble et qu’il y a un transport actif à travers cette dernière, deux phénomènes sont observés: la diminution de la fluorescence de la pyranine (car MexB fait entrer des protons dans le premier type de liposome pour transporter le substrat) et l’augmentation de la fluorescence du substrat car ce dernier s’intercale dans l’ARN se trouvant dans le deuxième type de liposome. En mélangeant les deux types de liposomes, j’obtiens une preuve de la reconstitution in vitro de la pompe entière et j’ai mis en évidence qu’OprM s’ouvre en présence de MexA et MexB et que sa présence augmente l’activité de MexB.

Among the various mechanisms developed by the bacteria to counter to the effect of antibiotics, active efflux is on the front line. In Pseudomonas aeruginosa, a Gram negative bacteria, efflux transporters are organized as multicomponent systems where MexB, the pump located in the inner membrane, works in conjunction with MexA, a periplasmic protein, and OprM, an outer membrane protein. MexB is a proton motive force-dependent pump with broad substrate specificity. During my…

Advisors/Committee Members: Broutin, Isabelle (thesis director), Picard, Martin (thesis director).

Subjects/Keywords: Resistance aux antibiotiques; Pompe d’efflux; Protéine membranaire; Protéoliposome; Test fonctionnel; Multidrug resistance; Efflux pump; Membrane protein; Proteoliposome; Functional test; 572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Verchère, A. (2014). Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2014PA05P622

Chicago Manual of Style (16^th Edition):

Verchère, Alice. “Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa.” 2014. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed April 10, 2021. http://www.theses.fr/2014PA05P622.

MLA Handbook (7^th Edition):

Verchère, Alice. “Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa.” 2014. Web. 10 Apr 2021.

Vancouver:

Verchère A. Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2014. [cited 2021 Apr 10]. Available from: http://www.theses.fr/2014PA05P622.

Council of Science Editors:

Verchère A. Functional investigation of the efflux pump MexA–MexB-OprM of Pseudomonas aeruginosa : Etude fonctionnelle de la pompe d’efflux MexA-MexB-OprM de Pseudomonas aeruginosa. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2014. Available from: http://www.theses.fr/2014PA05P622

Universiteit Utrecht

24. Laffont, Céline Marielle. Factors Affecting the Disposition of Ivermectin in the Target Species.

Degree: 2002, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/292

► It was the aim of the thesis to contribute to the understanding of the diverse factors involved in the pharmacokinetics of ivermectin, a very potent… (more)

▼ It was the aim of the thesis to contribute to the understanding of the diverse factors involved in the pharmacokinetics of ivermectin, a very potent antiparasitic drug widely used in both human and veterinary medicine. Ivermectin is extensively eliminated in faeces as parent drug and less active metabolites, irrespective of species and route of administration. It is currently believed that biliary secretion is the major route for the elimination of parent ivermectin from blood. However, using validated in vitro (Caco-2 cells) and in situ (rat intestinal loops) models, we provide convincing evidence for an intestinal secretion of ivermectin from blood into the intestinal lumen. In the rat, intestinal secretion was even more important than biliary secretion in the overall elimination of parent ivermectin. These findings may initiate a re-appraisal of the disposition of ivermectin, particularly its distribution into the digestive tract, thereby allowing a better understanding of its clinical efficacy against gastrointestinal parasites. The above mentioned investigations also pointed towards the prominent role of P-glycoprotein (P-gp) in the intestinal secretion process, although other transport mechanisms (multidrug resistance-associated protein MRP2) may be involved. The relevance of these findings for veterinary target species was demonstrated by examining the P-gp function in cattle, sheep, goats, pigs and horses using a lymphocyte-based ex vivo model. P-gp activity was found in peripheral blood lymphocytes of all animal species studied, albeit at different levels. In addition, P-gp expression was shown in the intestines for all species. These results provide mechanistic support for the intestinal secretion of ivermectin and other P-gp substrates. Since wide interspecies variations in P-gp activity were observed, it can be expected that the contribution of this secretion mechanism may differ from one species to the other. Finally, we identified that physiological animal licking behaviour does obviously contribute to the disposition of ivermectin in cattle following topical application. Under our experimental conditions, 58-87% of the dose (500 mu-g/kg) applied topically over the back of cattle was actually ingested by licking, while only 10% of the dose was absorbed through the skin. Approximately 70% of the ingested ivermectin was not absorbed orally and transited directly into faeces, increasing by 5-fold the environmental burden of biologically active ivermectin. Our results suggest that the systemic exposure of topically-treated animals is related to their ability to lick themselves or each other. Furthermore, pharmacokinetic modeling was used to predict ivermectin disposition in cattle under various conditions of oral and/or percutaneous exposure. Our simulations suggest that non-treated cattle could get easily contaminated with ivermectin by social contact (allo-licking) with topically-treated animals present in the same herd. In conclusion, our findings may stimulate further investigations towards the…

Subjects/Keywords: Diergeneeskunde; ivermectin; intestinal secretion; faecal elimination; P-glycoprotein (P-gp); multidrug resistance-associated protein 2 (MRP2); rat intestinal loops; Caco-2 cells; licking behaviour; endectocide

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Laffont, C. M. (2002). Factors Affecting the Disposition of Ivermectin in the Target Species. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/292

Chicago Manual of Style (16^th Edition):

Laffont, Céline Marielle. “Factors Affecting the Disposition of Ivermectin in the Target Species.” 2002. Doctoral Dissertation, Universiteit Utrecht. Accessed April 10, 2021. http://dspace.library.uu.nl:8080/handle/1874/292.

MLA Handbook (7^th Edition):

Laffont, Céline Marielle. “Factors Affecting the Disposition of Ivermectin in the Target Species.” 2002. Web. 10 Apr 2021.

Vancouver:

Laffont CM. Factors Affecting the Disposition of Ivermectin in the Target Species. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2002. [cited 2021 Apr 10]. Available from: http://dspace.library.uu.nl:8080/handle/1874/292.

Council of Science Editors:

Laffont CM. Factors Affecting the Disposition of Ivermectin in the Target Species. [Doctoral Dissertation]. Universiteit Utrecht; 2002. Available from: http://dspace.library.uu.nl:8080/handle/1874/292

25. Laffont, Céline Marielle. Factors Affecting the Disposition of Ivermectin in the Target Species.

Degree: 2002, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/292 ; URN:NBN:NL:UI:10-1874-292 ; 1874/292 ; URN:NBN:NL:UI:10-1874-292 ; https://dspace.library.uu.nl/handle/1874/292

► It was the aim of the thesis to contribute to the understanding of the diverse factors involved in the pharmacokinetics of ivermectin, a very potent… (more)

▼ It was the aim of the thesis to contribute to the understanding of the diverse factors involved in the pharmacokinetics of ivermectin, a very potent antiparasitic drug widely used in both human and veterinary medicine. Ivermectin is extensively eliminated in faeces as parent drug and less active metabolites, irrespective of species and route of administration. It is currently believed that biliary secretion is the major route for the elimination of parent ivermectin from blood. However, using validated in vitro (Caco-2 cells) and in situ (rat intestinal loops) models, we provide convincing evidence for an intestinal secretion of ivermectin from blood into the intestinal lumen. In the rat, intestinal secretion was even more important than biliary secretion in the overall elimination of parent ivermectin. These findings may initiate a re-appraisal of the disposition of ivermectin, particularly its distribution into the digestive tract, thereby allowing a better understanding of its clinical efficacy against gastrointestinal parasites. The above mentioned investigations also pointed towards the prominent role of P-glycoprotein (P-gp) in the intestinal secretion process, although other transport mechanisms (multidrug resistance-associated protein MRP2) may be involved. The relevance of these findings for veterinary target species was demonstrated by examining the P-gp function in cattle, sheep, goats, pigs and horses using a lymphocyte-based ex vivo model. P-gp activity was found in peripheral blood lymphocytes of all animal species studied, albeit at different levels. In addition, P-gp expression was shown in the intestines for all species. These results provide mechanistic support for the intestinal secretion of ivermectin and other P-gp substrates. Since wide interspecies variations in P-gp activity were observed, it can be expected that the contribution of this secretion mechanism may differ from one species to the other. Finally, we identified that physiological animal licking behaviour does obviously contribute to the disposition of ivermectin in cattle following topical application. Under our experimental conditions, 58-87% of the dose (500 mu-g/kg) applied topically over the back of cattle was actually ingested by licking, while only 10% of the dose was absorbed through the skin. Approximately 70% of the ingested ivermectin was not absorbed orally and transited directly into faeces, increasing by 5-fold the environmental burden of biologically active ivermectin. Our results suggest that the systemic exposure of topically-treated animals is related to their ability to lick themselves or each other. Furthermore, pharmacokinetic modeling was used to predict ivermectin disposition in cattle under various conditions of oral and/or percutaneous exposure. Our simulations suggest that non-treated cattle could get easily contaminated with ivermectin by social contact (allo-licking) with topically-treated animals present in the same herd. In conclusion, our findings may stimulate further investigations towards the…

Subjects/Keywords: ivermectin; intestinal secretion; faecal elimination; P-glycoprotein (P-gp); multidrug resistance-associated protein 2 (MRP2); rat intestinal loops; Caco-2 cells; licking behaviour; endectocide

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Laffont, C. M. (2002). Factors Affecting the Disposition of Ivermectin in the Target Species. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/292 ; URN:NBN:NL:UI:10-1874-292 ; 1874/292 ; URN:NBN:NL:UI:10-1874-292 ; https://dspace.library.uu.nl/handle/1874/292

Chicago Manual of Style (16^th Edition):

Laffont, Céline Marielle. “Factors Affecting the Disposition of Ivermectin in the Target Species.” 2002. Doctoral Dissertation, University Utrecht. Accessed April 10, 2021. https://dspace.library.uu.nl/handle/1874/292 ; URN:NBN:NL:UI:10-1874-292 ; 1874/292 ; URN:NBN:NL:UI:10-1874-292 ; https://dspace.library.uu.nl/handle/1874/292.

MLA Handbook (7^th Edition):

Laffont, Céline Marielle. “Factors Affecting the Disposition of Ivermectin in the Target Species.” 2002. Web. 10 Apr 2021.

Vancouver:

Laffont CM. Factors Affecting the Disposition of Ivermectin in the Target Species. [Internet] [Doctoral dissertation]. University Utrecht; 2002. [cited 2021 Apr 10]. Available from: https://dspace.library.uu.nl/handle/1874/292 ; URN:NBN:NL:UI:10-1874-292 ; 1874/292 ; URN:NBN:NL:UI:10-1874-292 ; https://dspace.library.uu.nl/handle/1874/292.

Council of Science Editors:

Laffont CM. Factors Affecting the Disposition of Ivermectin in the Target Species. [Doctoral Dissertation]. University Utrecht; 2002. Available from: https://dspace.library.uu.nl/handle/1874/292 ; URN:NBN:NL:UI:10-1874-292 ; 1874/292 ; URN:NBN:NL:UI:10-1874-292 ; https://dspace.library.uu.nl/handle/1874/292

26. Bachas, Sharrol T. Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR.

Degree: 2014, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/37156

► Multidrug resistance (MDR) is conferred by multidrug (MD) transporters and MD-responsive gene regulators. Intriguingly, regulation of MD transporters and gene regulators depend on interactions with… (more)

▼ Multidrug resistance (MDR) is conferred by multidrug (MD) transporters and MD-responsive gene regulators. Intriguingly, regulation of MD transporters and gene regulators depend on interactions with numerous unrelated chemical structures. This process is called “MD recognition” and is the crucial step that controls the MDR induction. In the past decade, structural studies of MD gene regulators bound to diverse ligands illuminated the process of MD recognition. From these studies, two mechanisms of MD recognition were proposed. Although different, these mechanisms demonstrate the general features that govern MD recognition. However, how MDR proteins are regulated by MD recognition remains a mystery. In this dissertation, connect MD recognition and MD signaling by combining results from structural and biochemical studies on the MD gene regulator, BmrR. We identified novel principles that explain how BmrR recognizes and efficiently responds to unrelated drugs. We believe these principles are adopted by other MDR proteins. In chapter 1, we survey the MD recognition properties of various MDR-associated gene regulators whose structures have been determined. In addition, we discuss how the properties of MD recognition pockets contribute to multispecificity. In Chapter 2, we describe the structural basis of MD recognition by BmrR. We define a novel mechanism of MD recognition termed the “alternative model”. In addition, we discuss unusual drug-binding modes and discuss their physiological consequences. Finally, we extend our to uncharacterized MDR proteins. Currently, the mechanism of signaling by BmrR and other MDR proteins is still speculative. We have conducted in vitro transcription studies on BmrR response to determine how ligand properties control MD signaling by BmrR. In Chapter 3, we discuss the importance of cationic selectivity in BmrR signaling. In addition, we discuss an uncoupled response mechanism that provides efficient MD responses to dissimilar xenobiotics. In Chapter 4, we explore the mechanism of gene activation by BmrR. We present preliminary results on the effects of inducers and non-inducers on BmrR promoter recognition. Furthermore, we analyze how inducers and non-inducers affect DNA binding and RNA polymerase recruitment. Finally, we analyze the role of ligand-induced promoter bending and DNA distortion in transcription activation by BmrR. Advisors/Committee Members: Leahy, Daniel (advisor).

Subjects/Keywords: Multidrug resistance; Multidrug recogniton,Multidrug signaling; Transcriptional activation; MerR family

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bachas, S. T. (2014). Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37156

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bachas, Sharrol T. “Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR.” 2014. Thesis, Johns Hopkins University. Accessed April 10, 2021. http://jhir.library.jhu.edu/handle/1774.2/37156.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bachas, Sharrol T. “Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR.” 2014. Web. 10 Apr 2021.

Vancouver:

Bachas ST. Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Apr 10]. Available from: http://jhir.library.jhu.edu/handle/1774.2/37156.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bachas ST. Multidrug recognition and Multidrug transcription activation by the gene regulator, BmrR. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37156

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Utah

27. Kim, Dongin. pH-Sensitive Micelle for Multidrug Resistant Tumors.

Degree: PhD, Pharmaceutics & Pharmaceutical Chemistry;, 2010, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/2149/rec/881

► The goal of this hypothesis-driven application is to develop a polymeric micelle that targets multidrug resistant (MDR) tumors via pH sensitivity. The micelles target tumors… (more)

▼ The goal of this hypothesis-driven application is to develop a polymeric micelle that targets multidrug resistant (MDR) tumors via pH sensitivity. The micelles target tumors that overexpressed folate receptors on their surface, and internalized into the tumor cells by folate receptor-mediated endocytosis. They also evade P-glycoprotein pumps on the surface of MDR tumors. After cellular internalization, the micelles release the encapsulated drug (doxorubicin: DOX) in response to pH changes (extracellular tumor pH -7.0 or endosomal pH -6.0). Concurrent with the release of the drug, the endosomal membrane disruption by polyhistidine prevents other resistance mechanisms, including drug sequestration and endosome recycling (exocytosis). Two generations of pH-sensitive micelles have been developed and tested. The first generation expected to be sensitive at the extracellular tumor pH (-7.0) involved a poly(L-histidine) (MW: 5K) (polyHis) core. The second generation composed of a poly(histidine(His)-co-phenylalanine(Phe)) (poly(His-co-Phe)) (MW: 5K) core is expected to be sensitive at the endosomal pH (-6.0) due to the increased hydrophobicity of phenylalanine compared with histidine. Both micelles use PEG (MW: 2K) strands as hydrophilic shell. To adjust the micelle pH sensitivity at pH 7.0 or pH 6.0, a mixed micelle formulation method was utilized by adding poly(L-lactide) (MW: 3K)-/?-PEG (MW: 2K) with a folate receptor (FR) ligand attached (PLLA-b-PEG-folate). DOX was loaded into both the mixed micelle formulations (polyHis-b-PEG/PLLA-b- PEG-folate (80/20 wt/wt%) and poly(His-co-Phe)-£-PEG/PLLA-£-PEG-folate (80/20 wt/wt%)) using the conventional dialysis method. Both DOX-loaded micelles had a particle size distribution ~ 100 nm and stable at pH 8.0 (micelle formulation pH) and 7.4 (physiological blood pH), but destabilized at pH 7.0 or at pH 6.0. Their pH sensitivity was confirmed by changes in particle size, transmittance, and critical micelle concentration, illustrating drug release at lower pHs. In vitro cellular experiments and in vivo studies demonstrated the feasibility of pH-sensitive micelles, and confirmed the advantages of pH-sensitive micelles over pH-insensitive micelles (PLLA-b-PEG/PLLA- 6-PEG-folate (80/20 wt/wt%)) or the free drug (DOX). In summary, poly(L-histidine)-based pH-sensitive micelles have great potential as a tumor-killing platform. However, more investigations into future clinical applications are needed because of the heterogeneous nature of biological tumors and tumor stem cells.

Subjects/Keywords: Micelles; Cancer; Multidrug Resistance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kim, D. (2010). pH-Sensitive Micelle for Multidrug Resistant Tumors. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/2149/rec/881

Chicago Manual of Style (16^th Edition):

Kim, Dongin. “pH-Sensitive Micelle for Multidrug Resistant Tumors.” 2010. Doctoral Dissertation, University of Utah. Accessed April 10, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/2149/rec/881.

MLA Handbook (7^th Edition):

Kim, Dongin. “pH-Sensitive Micelle for Multidrug Resistant Tumors.” 2010. Web. 10 Apr 2021.

Vancouver:

Kim D. pH-Sensitive Micelle for Multidrug Resistant Tumors. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2021 Apr 10]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/2149/rec/881.

Council of Science Editors:

Kim D. pH-Sensitive Micelle for Multidrug Resistant Tumors. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/2149/rec/881

Queens University

28. Myette, Robert Leonard. Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities .

Degree: Pathology and Molecular Medicine, 2011, Queens University

URL: http://hdl.handle.net/1974/6891

► MRPs mediate the ATP-dependent efflux of a structurally diverse array of compounds. Certain MRPs, including MRP1, MRP2 and MRP4, are involved in multidrug resistance in… (more)

▼ MRPs mediate the ATP-dependent efflux of a structurally diverse array of compounds. Certain MRPs, including MRP1, MRP2 and MRP4, are involved in multidrug resistance in tumour cells, while in non-malignant cells these MRPs can influence the distribution and/or elimination of many clinically important drugs. In addition, these MRPs mediate the efflux of physiological metabolites, many of which are conjugated organic anions. Modulation of the drug transporting activity of MRP1 (and to a lesser extent MRP2 and MRP4) has been a long sought after therapeutic objective. In this study, the modulatory abilities of five structurally distinct classes (I-V) of chalcogenopyrylium dyes (CGPs) were examined utilizing an in vitro assay which measures inhibition of radiolabeled estradiol glucuronide ([3H]E217βG) (a prototypical MRP substrate) uptake into inside-out membrane vesicles prepared from MRP-transfected human embryonic kidney (HEK) cells. Additionally, some CGPs were tested in a calcein efflux assay using intact MRP1-transfected HEK cells. Sixteen of 34 CGPs initially tested at a single concentration (≤30 μM) inhibited MRP1-mediated uptake by >50%, with IC50’s ranging from 0.7-7.6 μM. Of the 9 CGPs with IC50’s ≤2 μM, five belonged to Class I, two to Class II, and two to Class IV. When tested in the calcein efflux assay, only 4 of 16 CGPs inhibited MRP1-mediated cellular efflux by >50% (I-3, -4, -6, IV-1) while a fifth (II-5) inhibited efflux by 23%. These five CGPs were then tested as modulators of [3H]E217βG uptake by MRP2 and MRP4. Their effects on MRP2 transport activity were differential with two (I-4, I-6) inhibiting transport (IC50’s 2.0, 7.1 μM), two (I-3, IV-1) stimulating transport (>2-fold), while II-5 had no effect. On the other hand, all five CGPs inhibited [3H]E217βG uptake by MRP4, but less effectively than by MRP1. Finally, five analogs of CGP IV-1 were tested for their effects on MRP1, MRP2 and MRP4 [3H]E217βG uptake, but none were more efficacious than CGP IV-1. The CGPs tested here represent novel MRP1, MRP2 and MRP4 modulators with variable effects on transport activities. These CGPs may represent a new avenue for the development of clinically applicable modulators of MRP proteins involved in multidrug resistance.

Subjects/Keywords: Multidrug Resistance Proteins ; Chalcogenopyrylium Dyes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Myette, R. L. (2011). Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/6891

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Myette, Robert Leonard. “Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities .” 2011. Thesis, Queens University. Accessed April 10, 2021. http://hdl.handle.net/1974/6891.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Myette, Robert Leonard. “Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities .” 2011. Web. 10 Apr 2021.

Vancouver:

Myette RL. Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities . [Internet] [Thesis]. Queens University; 2011. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1974/6891.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Myette RL. Chalcogenopyrylium Dyes as Modulators of Multidrug Resistance Protein (MRP) 1, MRP2 and MRP4 Transport Activities . [Thesis]. Queens University; 2011. Available from: http://hdl.handle.net/1974/6891

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Oklahoma

29. Ntreh, Abigail. Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps.

Degree: PhD, 2016, University of Oklahoma

URL: http://hdl.handle.net/11244/44931

► Since the discovery of antibiotics, an ongoing race commenced between society’s ability to develop drugs and resistant bacteria. The combat has led to many drug… (more)

▼ Since the discovery of antibiotics, an ongoing race commenced between society’s ability to develop drugs and resistant bacteria. The combat has led to many drug discoveries, but it has also led to different mechanisms of the pathogens to evade cell death. One major means of bacterial resistance is the association of membrane proteins to expel substrates from within the cell and out into the extracellular space. Some protein complexes are able to oust various drugs irrespective of structure or function of the antimicrobial; these are the multidrug resistance (MDR) efflux pumps. In the Gram-negative bacteria, these complexes are made up of an inner membrane transport protein (IMP), a periplasmic adapter protein (PAP) also commonly known as the membrane fusion protein (MFP), and an outer membrane protein (OMP). This assembled conduit acts as a canal to channel substrates from within the cytoplasm – substrates are repositioned outside the nearly impenetrable outer barrier. Escherichia coli AcrAΒ-TolC is a constitutively expressed MDR pump. As one of the most studied systems, all three proteins have been crystalized, allowing for better understanding of the protein structures and properties. Many biochemical and structural experiments have aided predictions about protein-protein interactions and mechanisms of function of this protein complex. However, the homo-identity of all proteins in complex limits the isolation of roles and mechanistic characterization. The recently discovered TriABC-OpmH of Pseudomonas aeruginosa uniquely expresses two MFPs (TriA and TriB) and serves as a model system to study the assembly of efflux pumps and the function of MFPs in complex. In this study, we used the transporter protein AcrB to characterize kinetic parameters of efflux pump inhibitors (EPIs) provided by Basilea Pharmaceutica. Next, we used the TriABC complex as the means of studying the MFP-OMP amino acid interfaces. We investigated the role and assembly of TriA/B with the partnering OMP. We confirmed that MFPs stabilize interactions with the outer membrane channel protein, and we also assigned MFPs the role of opening the channel protein. Results isolated the role of each MFP within the functional dimeric complex. Additionally, we present low-resolution structures of TriABC showing different conformations of the TriAB MFPs. In vivo proteolysis experiments validate the structural findings, while presenting an OMP-dependent conformational change within one MFP. Together, this study provides new insight into the mechanism of MDR efflux complex, inspiring innovative drug targets and new drug designs to reciprocate and combat resistance of bacterial cells. Advisors/Committee Members: Zgurskaya, Elena (advisor), Cichewicz, Robert (committee member), Rice, Charles (committee member), Rybenkov, Valentin (committee member), Dunn, Anne (committee member).

Subjects/Keywords: mechanism; multidrug resistance; efflux pumps

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ntreh, A. (2016). Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/44931

Chicago Manual of Style (16^th Edition):

Ntreh, Abigail. “Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps.” 2016. Doctoral Dissertation, University of Oklahoma. Accessed April 10, 2021. http://hdl.handle.net/11244/44931.

MLA Handbook (7^th Edition):

Ntreh, Abigail. “Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps.” 2016. Web. 10 Apr 2021.

Vancouver:

Ntreh A. Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps. [Internet] [Doctoral dissertation]. University of Oklahoma; 2016. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/11244/44931.

Council of Science Editors:

Ntreh A. Mechanism and Interactions of Inner and Outer Membrane Components of RND Efflux Pumps. [Doctoral Dissertation]. University of Oklahoma; 2016. Available from: http://hdl.handle.net/11244/44931

University of Oxford

30. Ma, Jerome H. Y. Atomistic studies of the dynamics of P-glycoprotein and its ligands.

Degree: PhD, 2013, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:e2e2bbe0-d4ae-4351-b339-c8e02ef3d3d9 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658390

► A signifficant obstacle facing the healthcare industry is the phenomenon of multidrug resistance (MDR) in which a cell acquires simultaneous resistance to many unrelated drugs… (more)

▼ A signifficant obstacle facing the healthcare industry is the phenomenon of multidrug resistance (MDR) in which a cell acquires simultaneous resistance to many unrelated drugs that it has never been exposed to. At the molecular level, MDR can be characterised by a reduction of intracellular drug levels due to their active efflux by multidrug transporters such as P-glycoprotein (Pgp). Pgp is able to efflux a phenomenally wide variety of chemically unrelated drugs and causal relationships have been established between its expression and the acquisition of MDR to numerous anticancer and central nervous system (CNS) drugs. There has thus been much effort to understand the molecular biology of Pgp and how it functions. However, many aspects of its functioning remain unclear. From a drug discovery viewpoint, we have yet to fully understand what features make some drugs susceptible to Pgp-mediated efflux (substrates) and what makes others able to inhibit Pgp function (inhibitors). From a mechanistic viewpoint, it is still uncertain what the exact nature of Pgp's binding site is, the role of ATP binding and hydrolysis in transport and how both of these interplay with ligand binding. The work presented in this thesis attempts to answer these questions from two perspectives. Firstly the mouse Pgp crystal structure [PDB 3G60] was used as a unique starting point for molecular dynamics (MD) simulations to characterise the dynamics and conformational exibility of Pgp, properties believed to be integral to its function. The simulations revealed Pgp to be a highly dynamic molecule at both its transmembrane (TM) and nucleotide binding domains (NBDs). The latter exhibited a conformational asymmetry that supports the Constant Contact model of ATPase activity. In the presence of the Pgp substrate, daunorubicin, the NBDs exhibited tighter asymmetric dimerisation leading to increased affinity for ATP. In contrast, the presence of the Pgp inhibitor, QZ59-RRR led to NBD conformational changes that reduced their affinity for ATP. Thus providing an appealing mechanism for how QZ59-RRR inhibits Pgp ATPase activity. MD simulation was also used to provide atomic-detail interpretations of multiple binding stoichiometries of drug and lipid molecules observed by collaborator-led mass spectrometry experiments. This also provided opportunity to validate the Pgp simulations against novel experimental data. The second strand of the thesis explored the membrane permeation dynamics of CNS therapeutics in order to identify differences in protonation states, conformations, orientations and membrane localisation that might distinguish those that are Pgp substrates and from those that are not. These properties were studied using complementary MD simulation and nuclear magnetic resonance (NMR) techniques. The simulations revealed a novel set of criteria that in uence the likelihoodof a drug to 'flip-flop' across a membrane, a behaviour that may make drugs more susceptible to Pgp efflux. These observations were broadly consistent with the NMR experiments.…

Subjects/Keywords: 572; Biochemistry; Computational chemistry; Molecular dynamics; Nuclear magnetic resonance; Structural Biology; P-glycoprotein; Membrane protein; Lipid bilayer; Multidrug resistance

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ma, J. H. Y. (2013). Atomistic studies of the dynamics of P-glycoprotein and its ligands. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:e2e2bbe0-d4ae-4351-b339-c8e02ef3d3d9 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658390

Chicago Manual of Style (16^th Edition):

Ma, Jerome H Y. “Atomistic studies of the dynamics of P-glycoprotein and its ligands.” 2013. Doctoral Dissertation, University of Oxford. Accessed April 10, 2021. http://ora.ox.ac.uk/objects/uuid:e2e2bbe0-d4ae-4351-b339-c8e02ef3d3d9 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658390.

MLA Handbook (7^th Edition):

Ma, Jerome H Y. “Atomistic studies of the dynamics of P-glycoprotein and its ligands.” 2013. Web. 10 Apr 2021.

Vancouver:

Ma JHY. Atomistic studies of the dynamics of P-glycoprotein and its ligands. [Internet] [Doctoral dissertation]. University of Oxford; 2013. [cited 2021 Apr 10]. Available from: http://ora.ox.ac.uk/objects/uuid:e2e2bbe0-d4ae-4351-b339-c8e02ef3d3d9 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658390.

Council of Science Editors:

Ma JHY. Atomistic studies of the dynamics of P-glycoprotein and its ligands. [Doctoral Dissertation]. University of Oxford; 2013. Available from: http://ora.ox.ac.uk/objects/uuid:e2e2bbe0-d4ae-4351-b339-c8e02ef3d3d9 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658390

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