subject:(Aryl Hydrocarbon Receptor)

Oregon State University

1. Phillips, Jessica Lynne. Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression.

Degree: PhD, 2017, Oregon State University

URL: http://hdl.handle.net/1957/61709

► The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor of the basic helix-loop-helix PER/ARNT/SIM (bHLH/PAS) family and regulates a diverse set of genes. The… (more)

▼ The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor of the basic helix-loop-helix PER/ARNT/SIM (bHLH/PAS) family and regulates a diverse set of genes. The AhR is best known for directing the transcription of drug-metabolizing enzymes, particularly upon activation by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs). However, the AhR also regulates gene programs upstream of organismal development, cellular differentiation, cell proliferation, and programmed cell death. The roles of AhR in mediating cellular fate coupled with its ability to respond to both exogenous and endogenous chemical signals make its behavior in the context of cancer particularly interesting. Recently, we reported that low expression of AhR correlates with poor prognosis for breast cancer patients, adding to the accumulating evidence that AhR is able to mediate tumor suppressive effects in tissues. The central hypothesis of this research is that the aryl hydrocarbon receptor functions as a tumor suppressor, and that the tumor suppressive activities of AhR can be therapeutically activated with selective AhR ligands. To test our hypothesis, we developed AhR-knockout mice lacking the tumor suppressor protein p53, mimicking the most common mutation event in the development of human cancers. The absence of AhR increased the tumor burden, tumor spectrum and reduced survival in p53-deficient mice, supporting a tumor modifier role for the AhR. Furthermore, the double-knockout of AhR and p53 resulted in reduced embryonic survival and neonatal fitness. These findings suggest important roles for the AhR in tumor suppression and development, and have significant clinical implications. To test the hypothesis that AhR is a molecular target for anti-cancer therapeutics, we screened chemical libraries for small molecules capable of both activating the AhR and inhibiting the growth of cancer cells. Of interest were the compounds that caused growth arrest or apoptosis in triple-negative breast cancer (TNBC) cells, as patients with TNBC have an extremely bleak prognosis characterized by poor responses to currently available therapeutics and a rapid rate of relapse. A short list of compounds that induced AhR-dependent anti-cancer effects was investigated to determine their mechanisms of action. One compound activated AhR-dependent transcription of cyclin-dependent kinase inhibitor 1B (CDKN1B/p27Kip1), a cell cycle inhibitor and a tumor suppressor. As transcriptional regulation of p27Kip1 is a poorly understood phenomenon with implications for cancer treatment, we performed promoter analyses to determine regions critical to regulation of p27Kip1, and found evidence of transcriptional activation of p27Kip1 by the AhR. Given the potential for drug development, we then investigated the structural analogs of the p27Kip1-inducing compound for activation of AhR and subsequent transcriptional induction of p27Kip1, and restriction of TNBC cell growth. We selected ten analogs from a list of… Advisors/Committee Members: Kolluri, Siva K. (advisor), Buermeyer, Andrew B. (committee member).

Subjects/Keywords: Aryl hydrocarbon receptor

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APA (6^th Edition):

Phillips, J. L. (2017). Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/61709

Chicago Manual of Style (16^th Edition):

Phillips, Jessica Lynne. “Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression.” 2017. Doctoral Dissertation, Oregon State University. Accessed March 04, 2021. http://hdl.handle.net/1957/61709.

MLA Handbook (7^th Edition):

Phillips, Jessica Lynne. “Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression.” 2017. Web. 04 Mar 2021.

Vancouver:

Phillips JL. Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression. [Internet] [Doctoral dissertation]. Oregon State University; 2017. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1957/61709.

Council of Science Editors:

Phillips JL. Roles for the Aryl Hydrocarbon Receptor in Tumor Suppression. [Doctoral Dissertation]. Oregon State University; 2017. Available from: http://hdl.handle.net/1957/61709

Penn State University

2. DiNatale, Brett C. The role of the aryl hydrocarbon receptor in tumor cell phenotype.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11597

► The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor widely associated with its function in xenobiotic metabolism and its ability to bind environmental pollutants… (more)

▼ The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor widely associated with its function in xenobiotic metabolism and its ability to bind environmental pollutants in the polycyclic aromatic hydrocarbon family such as benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Upon ligand binding, the AHR translocates to the nucleus, exchanges its chaperone complex for its heterodimerization partner, the aryl hydrocarbon receptor nuclear translocator, and binds to dioxin response elements (DREs) in the promoter of target genes, driving transcription. However, researchers have tied the AHR to a variety of cellular processes in addition to xenobiotic metabolism, not all of which occur through DRE binding and direct transcriptional activation. The studies presented here build upon the finding that combinatorial treatment with exogenous AHR ligands and IL1B leads to synergistic IL6 expression in some typically non-responsive tumor cell lines. The overall hypothesis was that the AHR plays a molecular role in IL6 transcription and represents a viable point of treatment to mediate tumor cell signaling. Analysis of the mechanism by which these two signals mediate IL6 induction revealed that the liganded AHR binds to DREs far upstream from the IL6 promoter, yet plays a role in the de-repression of the chromatin of the proximal promoter through dismissal of co-repressor complexes. Following this, IL1B-induced NFkB activity is able to positively affect transcription of the IL6 gene. Subsequently, the role played by the AHR in the relatively high basal and readily inducible cytokine expression of head and neck squamous cell carcinoma (HNSCC) cell lines was assessed. Multiple HNSCC cell lines derived from various loco-regional tumors showed a similar state of IL6 de-repression with AHR occupancy of the promoter in the absence of exogenous ligand. This promoter configuration could be reversed and transcription repressed through treatment of cells with an AHR antagonist and the resultant decrease in receptor occupancy of the IL6 promoter. Next, the hypothesis was tested that basal AHR occupancy of the IL6 promoter in HNSCC cell lines is indicative of a constitutive level of receptor activity, and that the role of the AHR in various cellular processes that enhance tumor cell phenotype were similarly occurring. Treatment of HNSCC cell lines with AHR antagonists decreased tumor cell proliferation, migration, invasive ability, and prevented the increase of an integral protein for a chemotherapy efflux pump. The significance of the results presented in these studies reflects on both the field of AHR biology and the potential for AHR-targeted treatment in cancer, including HNSCC. Uncovering a mechanism whereby AHR activation is one of two signals required for gene regulation opens a new field of research into combinatorial effects of the receptor and points to previously undocumented genes as being AHR targets with or without DREs in the proximal promoter. Finally, AHR antagonist treatment is a viable… Advisors/Committee Members: Gary H Perdew, Dissertation Advisor/Co-Advisor, Gary H Perdew, Committee Chair/Co-Chair, Jeffrey Maurice Peters, Committee Member, Craig Richard Baumrucker, Committee Member, Andrea Marie Mastro, Committee Member, Kumble Sandeep Prabhu, Committee Member.

Subjects/Keywords: ahr; aryl hydrocarbon receptor; cancer

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APA (6^th Edition):

DiNatale, B. C. (2011). The role of the aryl hydrocarbon receptor in tumor cell phenotype. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11597

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):

DiNatale, Brett C. “The role of the aryl hydrocarbon receptor in tumor cell phenotype.” 2011. Thesis, Penn State University. Accessed March 04, 2021. https://submit-etda.libraries.psu.edu/catalog/11597.

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

MLA Handbook (7^th Edition):

DiNatale, Brett C. “The role of the aryl hydrocarbon receptor in tumor cell phenotype.” 2011. Web. 04 Mar 2021.

Vancouver:

DiNatale BC. The role of the aryl hydrocarbon receptor in tumor cell phenotype. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 04]. Available from: https://submit-etda.libraries.psu.edu/catalog/11597.

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

Council of Science Editors:

DiNatale BC. The role of the aryl hydrocarbon receptor in tumor cell phenotype. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11597

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

Cornell University

3. Mohinta, Sonia. Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function.

Degree: PhD, Immunology, 2014, Cornell University

URL: http://hdl.handle.net/1813/36177

► A number of autoimmune and chronic inflammatory diseases are related to environmental stress. Aryl hydrocarbon receptor (AHR) is regarded as an environmental sensor integrating immune… (more)

▼ A number of autoimmune and chronic inflammatory diseases are related to environmental stress. Aryl hydrocarbon receptor (AHR) is regarded as an environmental sensor integrating immune responses with environmental stress and thereby influencing the extent of host immune response. The physiological role of AHR, particularly, in the immune response remains a key question after the discovery that AHR can modulate Th17/Treg axis in a ligand specific manner. However, discovery of a non-DRE mediated AHR activation in addition to its canonical DRE-mediated pathway further adds to this complexity thereby necessitating a more critical approach in delineating the role of AHR in the context of Th17/Treg balance. Selective AHR modulators (SAHRMs) are a recently identified class of compounds that are capable of binding to AHR and repress cytokine- driven gene expression without activating DRE-driven responses We have used three classes of AHR ligands namely agonist, antagonist and partial antagonist (SAHRM) to delineate the role of AHR in the context of Th17/Treg regulation both in vitro and in vivo. Here, we show that inhibition of the DRE-driven response is sufficient to suppress the Th17 differentiation. Also, we show that the suppression of Treg differentiation is dependent on the inhibition of the non-DRE mediated pathway. We have also delineated the role of DRE vs non-DRE driven responses of Th17 regulation in both an acute vs a chronic Th17 mediated diseases. In an acute inflammation using C. rodentium model of IBD (Inflammatory Bowel Disease) AHR agonist enhanced Th17 production and thereby promoted resolution of infection. On the other hand, using S. rectivirgula in a chronic mouse model of Hypersensitivity Pneumonitis we show that inhibition of DRE and /or non-DRE mediated response had minimal effect on IL-17A production but precludes Th17 plasticity by enabling secretion of alternate lineage antiinflammatory cytokines. This work has profound implication in pharmacological intervention in autoimmune and chronic inflammatory diseases by developing AHR compounds which can modulate DRE and non-DRE driven responses. Advisors/Committee Members: August, Avery (chair), Denkers, Eric Young (committee member), Bynoe, Margaret S. (committee member).

Subjects/Keywords: Aryl Hydrocarbon Receptor; Th17; Tcell differentiation

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APA (6^th Edition):

Mohinta, S. (2014). Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36177

Chicago Manual of Style (16^th Edition):

Mohinta, Sonia. “Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function.” 2014. Doctoral Dissertation, Cornell University. Accessed March 04, 2021. http://hdl.handle.net/1813/36177.

MLA Handbook (7^th Edition):

Mohinta, Sonia. “Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function.” 2014. Web. 04 Mar 2021.

Vancouver:

Mohinta S. Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1813/36177.

Council of Science Editors:

Mohinta S. Role Of Aryl Hydrocarbon Receptor (Ahr) And The Effect Of Selective Ahr Modulators (Sahrms) On T Cell Differentiation And Effector Function. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36177

Penn State University

4. Smith, Kayla Jo. THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY.

Degree: 2017, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13833kjs5049

► Barrier tissues such as the skin and intestine are important for the first line of defense against injury and exposure to potentially harmful toxicants or… (more)

Subjects/Keywords: aryl hydrocarbon receptor; skin; intestine; inflammation; keratinocyte

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

APA (6^th Edition):

Smith, K. J. (2017). THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13833kjs5049

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):

Smith, Kayla Jo. “THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY.” 2017. Thesis, Penn State University. Accessed March 04, 2021. https://submit-etda.libraries.psu.edu/catalog/13833kjs5049.

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

MLA Handbook (7^th Edition):

Smith, Kayla Jo. “THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY.” 2017. Web. 04 Mar 2021.

Vancouver:

Smith KJ. THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY. [Internet] [Thesis]. Penn State University; 2017. [cited 2021 Mar 04]. Available from: https://submit-etda.libraries.psu.edu/catalog/13833kjs5049.

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

Council of Science Editors:

Smith KJ. THE ROLE OF THE ARYL HYDROCARBON RECEPTOR IN MODULATING SKIN AND INTESTINAL EPITHELIAL PHYSIOLOGY. [Thesis]. Penn State University; 2017. Available from: https://submit-etda.libraries.psu.edu/catalog/13833kjs5049

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

Penn State University

5. Narayanan, Gitanjali A. Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13944

► Modulation of aryl hydrocarbon receptor (AHR) activity by a class of ligands termed selective AHR modulators (SAhRMs) has been demonstrated to attenuate pro-inflammatory gene expression… (more)

▼ Modulation of aryl hydrocarbon receptor (AHR) activity by a class of ligands termed selective AHR modulators (SAhRMs) has been demonstrated to attenuate pro-inflammatory gene expression and signaling, including repression of cytokine-mediated induction of acute phase genes (e.g, Saa1) . These effects are observed to occur through an AHR-dependent mechanism that does not require canonical signaling through dioxin response elements (DREs). Previously, we have demonstrated that the SAhRM, 3´,4´-dimethoxy-α-napthoflavone (DiMNF) can repress the cytokine-mediated induction of complement factor genes. Here, we report that activation of the AHR with DiMNF can suppress the cytokine-mediated induction of the membrane complement regulatory protein (mCRP) CD55, which, when expressed on host cells, facilitates the decay of the complement component 3 (C3) convertase, thereby protecting the cell from complement mediated lysis. Furthermore, we also demonstrate that the cytokine-mediated expression of the mCRP, CD46, is also repressed by DiMNF. Tumor cells often exhibit elevated CD55 and CD46 expression on the cell surface in the inflammatory microenvironment of the tumor and it is thought that such enhanced expression represents a means of escaping immune surveillance. DiMNF can repress the cytokine-mediated induction of CD55 mRNA and protein. Luciferase reporter analysis have identified possible response elements on the CD55 promoter, which may be targets for this repression. CD97 is the receptor for CD55 and this binding has been shown to play a role in the development of inflammation and leukocyte trafficking, as well as stimulate tumor cell migration and angiogenesis. We report here that DiMNF is capable of repressing cytokine-mediated induction of CD97 expression in addition to CD46 and CD55. A C3 deposition assay with [125I]-C3 revealed that repression of cytokine-mediated CD55 expression by DiMNF led to an increase of C3 deposition on the surface of Huh7 cells, which would likely stimulate the formation of the membrane attack complex (MAC) and lead to complement-mediated lysis. We thereby suggest that SAhRMs such as DiMNF have therapeutic potential in regulating the immune response to tumor formation. Advisors/Committee Members: Gary H Perdew, Thesis Advisor/Co-Advisor.

Subjects/Keywords: Aryl Hydrocarbon Receptor; Complement; CD55; DiMNF

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

APA (6^th Edition):

Narayanan, G. A. (2012). Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13944

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):

Narayanan, Gitanjali A. “Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression.” 2012. Thesis, Penn State University. Accessed March 04, 2021. https://submit-etda.libraries.psu.edu/catalog/13944.

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

MLA Handbook (7^th Edition):

Narayanan, Gitanjali A. “Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression.” 2012. Web. 04 Mar 2021.

Vancouver:

Narayanan GA. Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 04]. Available from: https://submit-etda.libraries.psu.edu/catalog/13944.

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

Council of Science Editors:

Narayanan GA. Selective Modulation of the AH Receptor Leads to Repression of Complement Factor Gene Expression. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13944

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

University of Houston

6. Butler, Ryan 1986-. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.

Degree: PhD, Biology, 2013, University of Houston

URL: http://hdl.handle.net/10657/956

► Ligand-activated transcription factors are a diverse group of proteins that are involved a variety of physiological processes. The purpose of these studies was to investigate… (more)

▼ Ligand-activated transcription factors are a diverse group of proteins that are involved a variety of physiological processes. The purpose of these studies was to investigate the aryl hydrocarbon receptor (AhR) knockout mouse and the effects of hormone replacement therapy on the postmenopausal breast in order to better understand the functions of the ligand-activated transcription factors AhR and estrogen receptor β (ERβ). In the first part of these studies, we investigated the AhR knockout mouse in order to further elucidate the physiological functions of AhR. These mice developed stones in their urinary bladders composed of 100% uric acid while the serum uric acid levels remained normal. We determined these stones were formed by the breakdown of DNA into uric acid from a large number of dying cells. These mice also develop fibrosis of their ventral prostates and a phenotype in the immune system similar to chronic myeloid leukemia. The second part of these studies was to investigate the effects of hormone replacement therapy on the histology and expression of various ligand-activated transcription factors in the postmenopausal breast. We treated postmenopausal women with estrogen or estrogen-progesterone therapy for 3 months and took biopsies of the breasts before and after treatment. Expression of several proteins including AhR, ERα, and ERβ were unchanged after treatment while expression of progesterone receptors was increased. Proliferation and breast density were unchanged by treatment in these breasts; however, we show possible mechanisms leading to proliferation and development of density in non-cancerous breast tissue. In conclusion, these studies revealed a role for AhR in prostatic development, uric acid formation, and leukemia, and have provided new information on the safety of short-term use of HRT. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Warner, Margaret (committee member), Ziburkus, Jokubas (committee member), Webb, Paul (committee member).

Subjects/Keywords: Aryl hydrocarbon receptor; Estrogen receptors; Transcription factors

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

APA (6^th Edition):

Butler, R. 1. (2013). Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/956

Chicago Manual of Style (16^th Edition):

Butler, Ryan 1986-. “Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.” 2013. Doctoral Dissertation, University of Houston. Accessed March 04, 2021. http://hdl.handle.net/10657/956.

MLA Handbook (7^th Edition):

Butler, Ryan 1986-. “Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ.” 2013. Web. 04 Mar 2021.

Vancouver:

Butler R1. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10657/956.

Council of Science Editors:

Butler R1. Physiological and pathological aspects of the ligand-activated transcription factors: AhR and ERβ. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/956

University of Toronto

7. Rajendra, Sharanya. The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha.

Degree: 2013, University of Toronto

URL: http://hdl.handle.net/1807/43310

►

TiPARP is a PARP-like mART that is induced by and negatively regulates AHR transactivation. Despite these insights, not much is known about TiPARP. This study… (more)

Subjects/Keywords: Aryl Hydrocarbon Receptor; Estrogen Receptor Alpha; TCDD; TiPARP; Gene Regulation; 0419

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

APA (6^th Edition):

Rajendra, S. (2013). The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/43310

Chicago Manual of Style (16^th Edition):

Rajendra, Sharanya. “The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha.” 2013. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/43310.

MLA Handbook (7^th Edition):

Rajendra, Sharanya. “The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha.” 2013. Web. 04 Mar 2021.

Vancouver:

Rajendra S. The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha. [Internet] [Masters thesis]. University of Toronto; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/43310.

Council of Science Editors:

Rajendra S. The Regulation of TiPARP by the Aryl Hydrocarbon Receptor, the Platelet-derived Growth Factor Receptor, and the Estrogen Receptor Alpha. [Masters Thesis]. University of Toronto; 2013. Available from: http://hdl.handle.net/1807/43310

University of Alberta

8. El Gendy, Mohamed, A M. Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source.

Degree: PhD, Faculty of Pharmacy and Pharmaceutical Sciences, 2012, University of Alberta

URL: https://era.library.ualberta.ca/files/f7623d21k

► Dioxins are widespread environmental contaminants that have been linked to a variety of deleterious effects on human health including increased cancer rates via aryl hydrocarbon… (more)

▼ Dioxins are widespread environmental contaminants that have been linked to a variety of deleterious effects on human health including increased cancer rates via aryl hydrocarbon receptor (AhR)-dependent mechanism. AhR is a transcription factor that regulates the expression of the carcinogen-activating enzyme, cytochrome P450 1A1 (CYP1A1). Activation of AhR and its regulated gene, CYP1A1, have been correlated with the incidence of several cancers. Therefore, the use of AhR antagonists has been proposed as a promising chemopreventative approach. Nonetheless, most of the currently used AhR antagonists are not specific to AhR and some of them act as partial agonists. Therefore, the search for new AhR antagonists is still in progress. The specific objectives of the present work were to identify new AhR modulators from a natural source. In this regard, first we demonstrated that Peganum harmala, a common traditional plant in Middle East, and North Africa, significantly inhibited the dioxin-mediated induction of CYP1A1 at mRNA, protein and activity levels using human and mouse hepatoma cells. The role of AhR was confirmed using AhR-dependent luciferase assay and electrophoretic mobility shift assay. Additionally, we identified two β-carboline alkaloids (harmine and harmaline) as the active constituents of the plant extract. Second, we demonstrated that harman, a common β-carboline in several foods and drinks and the parent structure of harmine, significantly induced CYP1A1 mainly through an AhR-dependent mechanism. Third, the active constituents of Peganum harmala extract, harmine and harmaline, and their metabolites, harmol and harmalol, significantly decreased the dioxin-mediated induction of CYP1A1 at mRNA, protein and activity levels via transcriptional (through AhR) and post-translational (through ubiquitin-proteasomal pathway as well as a direct inhibitory effect on CYP1A1 enzyme). Additionally, we demonstrated that harmine, harmol, and harmalol can act as direct antagonists for AhR, whereas harmalol affected AhR activation without a direct interfering with AhR binding to its ligands. Finally, we confirmed the effect of harmine and harmaline on dioxin-mediated induction of Cyp1a1 in vivo using the responsive C57BL/6 mouse strain. In conclusion, our data clearly demonstrate the promising effects of Peganum harmala, harmine, harmol, harmaline, and harmalol to prevent the toxicity and carcinogenicity of several AhR ligands.

Subjects/Keywords: Cytochrome P450 1A1; harmol; Aryl Hydrocarbon Receptor; harmalol; harmine; Peganum harmala; Aryl Hydrocarbon Receptor antagonists from natural source; harmaline; harman; Chemoprevention

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

APA (6^th Edition):

El Gendy, Mohamed, A. M. (2012). Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/f7623d21k

Chicago Manual of Style (16^th Edition):

El Gendy, Mohamed, A M. “Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source.” 2012. Doctoral Dissertation, University of Alberta. Accessed March 04, 2021. https://era.library.ualberta.ca/files/f7623d21k.

MLA Handbook (7^th Edition):

El Gendy, Mohamed, A M. “Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source.” 2012. Web. 04 Mar 2021.

Vancouver:

El Gendy, Mohamed AM. Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source. [Internet] [Doctoral dissertation]. University of Alberta; 2012. [cited 2021 Mar 04]. Available from: https://era.library.ualberta.ca/files/f7623d21k.

Council of Science Editors:

El Gendy, Mohamed AM. Identifying Aryl Hydrocarbon Receptor Modulators from a Natural Source. [Doctoral Dissertation]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/f7623d21k

INP Toulouse

9. Malaisé, Yann. Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders.

Degree: Docteur es, Pathologie, Toxicologie, Génétique et Nutrition, 2017, INP Toulouse

URL: http://www.theses.fr/2017INPT0119

► Le bisphénol A (BPA) est un perturbateur endocrinien couramment employé dans l’industrie agroalimentaire, en particulier pour les matériaux en contact des denrées alimentaires. Son utilisation… (more)

▼ Le bisphénol A (BPA) est un perturbateur endocrinien couramment employé dans l’industrie agroalimentaire, en particulier pour les matériaux en contact des denrées alimentaires. Son utilisation dans la fabrication de polycarbonates et de résines époxy, recouvrant la face interne des boîtes de conserve et des canettes, en fait un contaminant ubiquitaire de l’alimentation humaine. L’augmentation de l’exposition humaine à ce contaminant a été corrélée avec la récurrence de certains troubles comme l’intolérance alimentaire, l’obésité ou le diabète de type 2. Ces dernières années, une attention particulière a été portée sur sa capacité à perturber différentes fonctions physiologiques, dont celle du système immunitaire, après exposition périnatale à des niveaux environnementaux pertinents pour l’Homme. Dans une première étude, nous avons montré qu’une exposition périnatale au BPA à 50 µg/kg de poids corporel/jour induit une diminution de l’activité anti-microbienne corrélée à une chute de l’expression du lysozyme dans l’iléon de la descendance femelle. La perméabilité intestinale de ces individus augmente en association avec le niveau d’IFN- dans les muqueuses du côlon. De plus, nous observons une diminution des plasmocytes à IgA associée à une perte de sécrétion d’IgA dans les fèces, démontrant un défaut de la fonction barrière et des défenses de l’intestin chez la descendance BPA. De manière intéressante, une diminution de la fréquence des ILC3 intestinaux est observée chez ces individus, avec une augmentation du niveau d’IgG sanguin dirigé contre une E.coli commensale. Ces effets sont associés à un défaut de maturation et de capacité migratoire des cellules de la lamina propria (LP) et de la rate. L’exposition périnatale au BPA provoque une augmentation de la sécrétion d’IFN- et d’IL-17 après re-stimulation in vitro CD3/CD28 des cellules de la LP, et une réponse de type Th17 dans la rate. Réunis, ces effets confortent la capacité du BPA, lors d’une exposition périnatale, à induire une intolérance alimentaire chez la descendance femelle. Dans une seconde étude, nous avons mis en évidence que l’exposition périnatale au BPA, à la même dose, induit des perturbations de l’homéostasie du système immunitaire intestinal et systémique chez la descendance mâle au jour 45, via une diminution de la fréquence des Th1 et Th17 dans la LP et une augmentation de la réponse Th1 et Th17 dans la rate. Ces impacts apparaissent en parallèle avec une altération de la sensibilité au glucose, une diminution de la sécrétion d’IgA dans les fèces et un appauvrissement des bifodobacteria dans le microbiote intestinal de ces individus. L’ensemble de ces évènements précède l’infiltration de macrophages M1 pro-inflammatoires dans le tissu adipeux péri-gonadique, en association avec une diminution de la sensibilité à l’insuline et une augmentation du poids corporel apparaissant avec le vieillissement (jour 170) chez la descendance BPA. Cette étude longitudinale a permis de proposer une séquence d’évènements aboutissant à un phénotype obèse et au T2D… Advisors/Committee Members: Piriou-Guzylack, Laurence (thesis director), Houdeau, Eric (thesis director).

Subjects/Keywords: Bisphénols; Système immunitaire; Intestin; Désordres métaboliques; Aryl hydrocarbon receptor; Bisphenols; Immune system; Gut; Metabolic disorders; Aryl hydrocarbon receptor

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APA (6^th Edition):

Malaisé, Y. (2017). Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders. (Doctoral Dissertation). INP Toulouse. Retrieved from http://www.theses.fr/2017INPT0119

Chicago Manual of Style (16^th Edition):

Malaisé, Yann. “Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders.” 2017. Doctoral Dissertation, INP Toulouse. Accessed March 04, 2021. http://www.theses.fr/2017INPT0119.

MLA Handbook (7^th Edition):

Malaisé, Yann. “Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders.” 2017. Web. 04 Mar 2021.

Vancouver:

Malaisé Y. Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders. [Internet] [Doctoral dissertation]. INP Toulouse; 2017. [cited 2021 Mar 04]. Available from: http://www.theses.fr/2017INPT0119.

Council of Science Editors:

Malaisé Y. Caractérisation chez la souris adulte des impacts immuno-modulateurs des bisphénols après exposition périnatale : conséquences sur la fonction "barrière" de l'intestin et la susceptibilité aux désordres métaboliques : Characterization of immuno-modulatory impacts of bisphenols after perinatal exposure in adult mice : consequences on the gut barrier function and the susceptibility to metabolic disorders. [Doctoral Dissertation]. INP Toulouse; 2017. Available from: http://www.theses.fr/2017INPT0119

University of Toronto

10. Yang, Yang. Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells.

Degree: 2015, University of Toronto

URL: http://hdl.handle.net/1807/73180

►

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor best known for mediating the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).… (more)

Subjects/Keywords: Aryl hydrocarbon receptor (AHR); Aryl hydrocarbon receptor repressor (AHRR); Aryl hydrocarbon response element (AHRE); Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq); dioxin; DNA binding; 0383

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APA (6^th Edition):

Yang, Y. (2015). Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/73180

Chicago Manual of Style (16^th Edition):

Yang, Yang. “Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells.” 2015. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/73180.

MLA Handbook (7^th Edition):

Yang, Yang. “Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells.” 2015. Web. 04 Mar 2021.

Vancouver:

Yang Y. Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/73180.

Council of Science Editors:

Yang Y. Genome-wide Mapping and Analysis of Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Receptor Repressor (AHRR) Bound Regions in MCF-7 Human Breast Cancer Cells. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/73180

University of Toronto

11. Hunter, Sarah Rachel. Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids.

Degree: 2014, University of Toronto

URL: http://hdl.handle.net/1807/73165

►

The aryl hydrocarbon receptor (AHR) nuclear translocator (ARNT), a partner in the hypoxia and AHR signaling pathways, is induced in rat liver by dexamethasone (DEX),… (more)

Subjects/Keywords: aryl hydrocarbon receptor nuclear translocator; glucocorticoid receptor; glucocorticoids; pregnane X receptor; rat; signaling pathway; 0419

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APA (6^th Edition):

Hunter, S. R. (2014). Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/73165

Chicago Manual of Style (16^th Edition):

Hunter, Sarah Rachel. “Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids.” 2014. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/73165.

MLA Handbook (7^th Edition):

Hunter, Sarah Rachel. “Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids.” 2014. Web. 04 Mar 2021.

Vancouver:

Hunter SR. Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids. [Internet] [Masters thesis]. University of Toronto; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/73165.

Council of Science Editors:

Hunter SR. Induction of the Rat Hepatic Aryl Hydrocarbon Receptor Nuclear Translocator by Glucocorticoids. [Masters Thesis]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/73165

University of Toronto

12. Crosby, Michael. Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice.

Degree: 2017, University of Toronto

URL: http://hdl.handle.net/1807/79379

►

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that activate the aryl hydrocarbon receptor, triggering many biological effects typified by induction of cytochrome P450 1A1 (CYP1A1).… (more)

Subjects/Keywords: aryl hydrocarbon receptor; Cyp3a11; drug metabolism; drug metabolizing enzyme; P450; polycyclic aromatic hydrocarbon; 0419

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APA (6^th Edition):

Crosby, M. (2017). Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/79379

Chicago Manual of Style (16^th Edition):

Crosby, Michael. “Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice.” 2017. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/79379.

MLA Handbook (7^th Edition):

Crosby, Michael. “Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice.” 2017. Web. 04 Mar 2021.

Vancouver:

Crosby M. Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice. [Internet] [Masters thesis]. University of Toronto; 2017. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/79379.

Council of Science Editors:

Crosby M. Regulation of Hepatic CYP3A4 by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice. [Masters Thesis]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/79379

University of Otago

13. Kazantseva, Marina Grigorievna. Smoking, genes and inflammation .

Degree: 2012, University of Otago

URL: http://hdl.handle.net/10523/2496

► Rheumatoid arthritis (RA) is an, autoimmune disease where genetic predisposition and environmental factors increase the risk of developing RA and the severity of the disease.… (more)

▼ Rheumatoid arthritis (RA) is an, autoimmune disease where genetic predisposition and environmental factors increase the risk of developing RA and the severity of the disease. Cigarette smoking is the major recognised environmental risk factor, and there is a combined effect from smoking and the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype on the risk of developing RA. This study sought to establish any direct effect of smoking and/or the genetic predisposition on the inflammation driving RA and to identify biological mechanism(s) that might explain epidemiological data linking smoking, genetics and RA. The aim of initial work was to establish any involvement of aryl hydrocarbon receptor (AHR)-mediated mechanisms within inflamed rheumatoid tissues. The expression of AHR, CYP1A1 and AHRR genes were quantified by real-time PCR in twenty synovial and eighteen subcutaneous nodule tissues. Patient’s smoking status was established at the time tissue was obtained. The results show smoking causes significant AHR activation in joint synovial tissue, but not in rheumatoid nodule tissues. A subset of synovial DCs show activated AHR in smokers, consistent with the sensitivity of human mo-DCs stimulated with the AHR agonist, benzo(a)pyrene (BaP) in vitro. It is concluded that DCs within the joint synovium are the principal immune cells that respond to cigarette smoke exposure. Microarray analysis revealed that the expression of 547 synovial genes was up-regulated by smoking, including folate receptor 1 (FOLR1), matrix metalloproteinases (MMP)9, MMP11 and MMP14, TNF-superfamily members, TNFSF10/TRAIL and TNFRSF10B/TRAILR2 and transcription factors, RUNX1 and RUNX2. Cell motility and adhesion were the biological processes in synovium most affected by smoking. The expression of 307 synovial genes was down-regulated by smoking, including the vascular “protective” genes, KLF2 and eNOS, suggesting that endothelial function is affected by smoking with implications for vasculitis and the development of rheumatoid nodules associated with severe RA. Any effect of smoking and SE copy number on genes associated with AHR signalling and other immune-inflammatory genes was established. Results suggest there are solitary, reciprocal or synergistic effects from smoking and the SE in rheumatoid inflammation, which are gene dependent. Thus, smoking increases AHR activation in synovium; the SE has no effect. Furthermore, while smoking reduces IL17A expression in synovial tissue, indications are that SE copy number increases IL17A expression. In combination, smoking and the SE increase synovial MMP9 gene expression. Human promonocytic U937 cells were used to model the effect of BaP exposure on MMP9 expression. PMA-activated U937 cells acquire an ability to respond to BaP, including with increased MMP9 gene expression. AHR-specific siRNA, confirmed that AHR regulates MMP9 gene expression. Further data implicate different MMPs in rheumatoid tissue destruction. High MMP7 expression by macrophages occurs in a subset of nodule tissues.… Advisors/Committee Members: Hessian, Paul A (advisor).

Subjects/Keywords: rheumatoid arthritis; inflammation; smoking; aryl hydrocarbon receptor; matrix metalloproteinases

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APA (6^th Edition):

Kazantseva, M. G. (2012). Smoking, genes and inflammation . (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/2496

Chicago Manual of Style (16^th Edition):

Kazantseva, Marina Grigorievna. “Smoking, genes and inflammation .” 2012. Doctoral Dissertation, University of Otago. Accessed March 04, 2021. http://hdl.handle.net/10523/2496.

MLA Handbook (7^th Edition):

Kazantseva, Marina Grigorievna. “Smoking, genes and inflammation .” 2012. Web. 04 Mar 2021.

Vancouver:

Kazantseva MG. Smoking, genes and inflammation . [Internet] [Doctoral dissertation]. University of Otago; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10523/2496.

Council of Science Editors:

Kazantseva MG. Smoking, genes and inflammation . [Doctoral Dissertation]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2496

Universiteit Utrecht

14. Mooij, F.A. de. The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food.

Degree: 2015, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/309341

► Layman’s summary Everybody knows that eating vegetables and overall healthy food is beneficial for your health. In recent years advertisers also started to tell us… (more)

▼ Layman’s summary Everybody knows that eating vegetables and overall healthy food is beneficial for your health. In recent years advertisers also started to tell us that products such as Yakult© that contain bacteria can improve the wellbeing of our intestines1. This is why a lot of research has been going towards finding the mechanisms behind these healthy bacteria and the beneficial effects of healthy food. It is now suggested that there could be a link between these two. Our bodies are built of cells that obtain their energy from food. In our intestines we have a lot of bacteria that helps us digest our food. This may sound weird, but in contrast to bacteria in other parts of our body, bacteria in the intestine are not harmful as long as there is a state of symbiosis. The cells of our intestines are not able to use all the food that we eat because they lack the machinery to make little pieces of it that can get absorbed into the cells. That’s where our resident bacteria come in. They have different machinery that help us process certain types of food into the small pieces we need. When these small pieces of food are taken up by the intestinal cells, they can start processes within the cells by binding to receptors. For instance, this could lead to the development and activation of the immune system. This can help to keep the balance between the intestine and the resident bacteria. Recent research has shown us that an important receptor in this process is the Aryl Hydrocarbon Receptor (AhR). The AhR can assist in protecting our intestines from harm by activating part of our immune system. They do so by activating the cells to produce signaling molecules, one of the most important ones is interleukin 22 (IL-22). This IL-22 is on its own able to bind its own specific receptor on other cells thereby amplifying the signal and activating these cells to start secreting small proteins such as defensins. As the name suggests, these defensins are small proteins that can kill the bacteria. With the secretion of defensins the amount of bacteria can be controlled, hereby keeping the balance to provide symbiosis. Next to the activation of cells to produce defensins, the activation of the AhR also leads to the development of other cells from our immune system, thereby making sure that we are well protected in the long run. As described, via activation of the AhR we can modulate the health of our intestines. It is therefore very interesting to know how we can activate this receptor. It is now suggested that the small molecules that bind the AhR can come from our food. For instance, tryptophan, which is an amino acid, gets cut by the gut bacteria into kynurenine which is then able to bind and activate the AhR. A particular group of bacteria, the lactobacilli, are very able to contribute to this process. Additionally, small molecules derived from food such as broccoli and cabbage have been shown to activate the AhR. One of these molecules is known as indole-3-carbinol. In conclusion, activating the AhR in the intestines… Advisors/Committee Members: Loonen, Dr. L., Wichers, Prof. H., Pieters, Dr. R..

Subjects/Keywords: ahr; aryl hydrocarbon receptor; probiotics; microbiotics; indole-3-carbinol; tryptophan

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APA (6^th Edition):

Mooij, F. A. d. (2015). The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/309341

Chicago Manual of Style (16^th Edition):

Mooij, F A de. “The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food.” 2015. Masters Thesis, Universiteit Utrecht. Accessed March 04, 2021. http://dspace.library.uu.nl:8080/handle/1874/309341.

MLA Handbook (7^th Edition):

Mooij, F A de. “The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food.” 2015. Web. 04 Mar 2021.

Vancouver:

Mooij FAd. The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food. [Internet] [Masters thesis]. Universiteit Utrecht; 2015. [cited 2021 Mar 04]. Available from: http://dspace.library.uu.nl:8080/handle/1874/309341.

Council of Science Editors:

Mooij FAd. The Aryl Hydrocarbon receptor and intestinal immunity: an overview of ligands derived from microbial metabolism and food. [Masters Thesis]. Universiteit Utrecht; 2015. Available from: http://dspace.library.uu.nl:8080/handle/1874/309341

University of Rochester

15. Pena, Fanny Lys Casado. Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells.

Degree: PhD, 2011, University of Rochester

URL: http://hdl.handle.net/1802/15793

► The aryl hydrocarbon receptor (Ahr) mediates the toxicity of certain environmental pollutants including dioxins. Accidental dioxin exposure to humans has been correlated with blood malignancies… (more)

▼ The aryl hydrocarbon receptor (Ahr) mediates the toxicity of certain environmental pollutants including dioxins. Accidental dioxin exposure to humans has been correlated with blood malignancies such as leukemia and lymphoma. Dioxin exposure suppresses immune responses in mammals via Ahr by several mechanisms including altering the functional ability of hematopoietic progenitors to seed the thymus. Also, exposure alters population of the spleen and reconstitution of peripheral blood and bone marrow. The Ahr is a ligand-activated transcription factor without any established endogenous ligand or physiological role in hematopoietic cells. To explain the decreased reconstitution of bone marrow, I hypothesized that dioxin exposure alters the numbers of hematopoietic stem/progenitor cells and/or the trafficking of these populations to the bone marrow. Furthermore, I hypothesized that these cellular consequences of TCDD exposure are secondary to an alteration of transcriptionally regulated pathways related to cell-to-cell signaling and cellular movement. Colony-forming assays and competitive repopulation experiments were used to quantify sub-populations of LSKs. In vivo dioxin exposure increased the numbers of multipotent progenitors but did not change the numbers of functional hematopoietic stem cells (HSCs). Trafficking of LSKs to the bone marrow in vivo, and to the chemokine Cxcl12 in vitro were decreased. Transcripts involved in cell-to-cell signaling (Ccl3, Cd69, Cxcl2, Cox-2, Mmp8) and cellular movement (Scin, Mmp8), as well as hematological system development and function (Egr-1, Ccl3, Cd69, Cxcl2, Cox-2) were altered in TCDD-exposed LSKs. Altogether these data support a physiological role of the Ahr to regulate homeostasis in HSCs. Disruption of Ahr expression or activity may predispose more differentiated populations to acquire malignant behaviors and reduce the ability of HSCs to respond to stress or injury. The mechanism of action for an Ahr ligand to alter cell function and pathway-specific gene modulation of LSKs as defined in this work provides a rationale to examine possible preventive measures in populations exposed to Ahr ligands. Being the Ahr a ligand-activated transcription factor, therapeutic interventions that regulate the expansion, migration and differentiation of HSCs or selective modulation of specific-hematopoietic lineages may be explored.

Subjects/Keywords: Aryl Hydrocarbon Receptor; Hematopoiesis; Stem Cells; Toxicology; Dioxin

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APA (6^th Edition):

Pena, F. L. C. (2011). Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/15793

Chicago Manual of Style (16^th Edition):

Pena, Fanny Lys Casado. “Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells.” 2011. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/15793.

MLA Handbook (7^th Edition):

Pena, Fanny Lys Casado. “Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells.” 2011. Web. 04 Mar 2021.

Vancouver:

Pena FLC. Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells. [Internet] [Doctoral dissertation]. University of Rochester; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/15793.

Council of Science Editors:

Pena FLC. Activation of the Aryl Hydrocarbon Receptor Signaling by 2,3,7,8 Tetra-chlorodibenzo-p-dioxin (TCDD) Alters Cell Function and Pathway-specific Gene Modulation of Hematopoietic Stem/Progenitor Cells. [Doctoral Dissertation]. University of Rochester; 2011. Available from: http://hdl.handle.net/1802/15793

University of Rochester

16. Latchney, Sarah Elizabeth. Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis.

Degree: PhD, 2012, University of Rochester

URL: http://hdl.handle.net/1802/19821

► The ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; Dioxin) has been linked to neurotoxicity in humans and experimental animals. TCDD exerts its toxicity by binding to the… (more)

▼ The ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; Dioxin) has been linked to neurotoxicity in humans and experimental animals. TCDD exerts its toxicity by binding to the aryl hydrocarbon receptor (AhR), a ligand-activated bHLH/PAS transcription factor. Although the endogenous functions of AhR remain unknown, certain bHLH/PAS proteins have been implicated in cell proliferation, differentiation, and cell fate decisions. Therefore, it is conceivable that AhR plays similar roles during neurogenesis. TCDD, through binding and activating the AhR, causes numerous neurological deficits. However, the specific cellular targets and mechanisms of AhR-mediated TCDD neurotoxicity are not well defined. Our laboratory has determined that AhR is robustly expressed in multipotent neural progenitor cells (NPCs) during critical neurogenic periods, implicating a mechanistic link between TCDD-mediated toxicity and impaired brain development. This thesis project tested the hypothesis that NPCs are primary targets for AhR-mediated TCDD neurotoxicity. As a result, AhR activation by TCDD impairs neurogenesis. A corollary to this hypothesis is that AhR intrinsically regulates neurogenesis in the absence of an exogenous ligand. Studies with the C17.2 NPC model and primary cultures of NPCs from embryonic mouse forebrain demonstrate that NPCs possess an intact AhR pathway that is responsive to TCDD. In these in vitro studies, TCDD reduced NPC proliferation and interfered with neuronal differentiation by disrupting the expression of cell cycle regulatory molecules. Furthermore, in vivo TCDD exposure during a critical period of NPC expansion and peak AhR expression also diminished NPC birth in the ventricular zone of the embryonic forebrain, confirming our in vitro results. In adult animals, AhR-deficient mice exhibited significant impairments in contextual fear memory, while hippocampal-independent memory remained intact. AhR-deficient mice also exhibited reduced proliferation and neuronal differentiation of adult-born NPCs in the neurogenic dentate gyrus of the hippocampus. Moreover, modulation of AhR activity by TCDD in adult wild-type mice disrupted hippocampal-dependent contextual memory and reduced cell birth and neuronal differentiation. Our findings demonstrate the AhR is a novel transcriptional regulator during developmental and adult neurogenesis. As a result, modulation of AhR activity by TCDD precludes the AhR from performing its endogenous function, leading to neurotoxicity and dysfunction.

Subjects/Keywords: Hippocampus; Neurotoxicity; Neurogenesis; Neural Stem Cells; Dioxin; Aryl Hydrocarbon Receptor

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APA (6^th Edition):

Latchney, S. E. (2012). Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/19821

Chicago Manual of Style (16^th Edition):

Latchney, Sarah Elizabeth. “Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis.” 2012. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/19821.

MLA Handbook (7^th Edition):

Latchney, Sarah Elizabeth. “Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis.” 2012. Web. 04 Mar 2021.

Vancouver:

Latchney SE. Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis. [Internet] [Doctoral dissertation]. University of Rochester; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/19821.

Council of Science Editors:

Latchney SE. Pluripotent Neural Stem Cells are Targets for Dioxin Toxicity: Novel Roles for the Aryl Hydrocarbon Receptor during Neurogenesis. [Doctoral Dissertation]. University of Rochester; 2012. Available from: http://hdl.handle.net/1802/19821

University of Rochester

17. Bennett, John A. Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells.

Degree: PhD, 2015, University of Rochester

URL: http://hdl.handle.net/1802/30118

► All mature cell lineages of the peripheral blood and adaptive immune system are generated from bone marrow stem cells known as hematopoietic stem cells (HSCs).… (more)

▼ All mature cell lineages of the peripheral blood and adaptive immune system are generated from bone marrow stem cells known as hematopoietic stem cells (HSCs). Lack of aryl hydrocarbon receptor (AhR) signaling, or treatment with AhR agonists such as TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin) , has been shown to alter the phenotype and functional ability of HSCs, suggesting a role for the AhR in regulating HSC function and output. Most classical studies on AhR have been undertaken using TCDD or other xenobiotic ligands to modulate AhR activity. While these studies have revealed a wealth of information regarding AhR target genes and signaling networks in a variety of cell types (including HSCs), it has remained difficult to determine which endpoints / regulatory target genes are adaptive or toxic responses due to exposure to AhR ligands versus normal targets and functions under homeostatic conditions. Studies were performed using both global AhR-null allele (AhR-KO) mice as well as hematopoietic system restricted AhRfx/fxVav1-Cre (CKO) mice in order to better understand the HSC-intrinsic physiological role of AhR in regulating HSC function and output. These studies revealed a surprising lack of phenocopy between the two strains. Aged KO animals display an expansion of peripheral white blood cells which is not found in aged CKO animals. KO animals have enhanced levels of oxidative stress in bone marrow progenitors, as well as evidence of DNA damage and decreased expression of p16. CKO animals only display enhanced oxidative capacity at the time point examined. Microarray studies on long term HSCs were undertaken in order to examine the differences in cell signaling and gene expression that could be driving these unexpected differences in phenotype. The two strains display very little overlap in genes with differential expression relative to control at young ages, but become more similar with aging. Gene Set Enrichment Analysis revealed significant enrichment in a variety of gene sets that are related to HSC function, or involved in the etiology of certain diseases such as leukemia or myeloproliferation. A subset of differentially expressed genes that changed expression due to both aging and lack of AhR expression (Pdgf-D, Smo, Zbtb37, and Zfp382), and that contain AhR binding sites in their upstream regulatory regions, change expression when AhR expression is silenced in wild-type hematopoietic cells. Taken together, these data reveal potential genes that AhR may intrinsically regulate in HSCs throughout aging of the hematopoietic system. Given the lack of phenocopy and the small degree of overlap differentially expressed genes in HSCs between KO and CKO mice, these data also implicate AhR in non-hematopoietic stromal cells of the bone marrow as having a regulatory effect on HSC function and output.

Subjects/Keywords: AhR; Aryl Hydrocarbon Receptor; Hematopoiesis; Hematopoietic Stem Cell

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

APA (6^th Edition):

Bennett, J. A. (2015). Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/30118

Chicago Manual of Style (16^th Edition):

Bennett, John A. “Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells.” 2015. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/30118.

MLA Handbook (7^th Edition):

Bennett, John A. “Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells.” 2015. Web. 04 Mar 2021.

Vancouver:

Bennett JA. Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/30118.

Council of Science Editors:

Bennett JA. Lack of Aryl Hydrocarbon Receptor Alters Gene Expression and Functional Capacity of Murine Hematopoietic Stem Cells. [Doctoral Dissertation]. University of Rochester; 2015. Available from: http://hdl.handle.net/1802/30118

University of Rochester

18. Boule , Lisbeth A. Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life.

Degree: PhD, 2015, University of Rochester

URL: http://hdl.handle.net/1802/30128

► Developmental exposures have been shown to alter immune-mediated processes later in life, yet the mechanism by which this occurs is unknown. In fact, in most… (more)

▼ Developmental exposures have been shown to alter immune-mediated processes later in life, yet the mechanism by which this occurs is unknown. In fact, in most cases it is unclear which cell types and molecular machinery are affected. Many studies have examined early life exposures to chemicals that activate the aryl hydrocarbon receptor (AhR). Cells of the immune system express this receptor, and AhR activation in the fully mature immune system (i.e., non-developmental exposure) alters CD4+ T cell-dependent immune responses. However, little is known about how activation of the AhR during development changes the function of CD4+ T cells in adult offspring. Therefore, using mouse models of human disease, we determined whether developmental exposure to the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects CD4+ T cell responses in adult offspring. For the majority of work in this project, we used influenza A virus infection to initiate an immune response. Developmentally exposed adult mice infected with influenza virus had fewer conventional effector CD4+ T cells in draining lymph nodes of the lung, yet an increase in regulatory CD4+ T cells (Tregs). In contrast, the lungs of these mice had an increase in all CD4+ T cell subsets. Using a combination of tools, including adoptive transfers and the cre-loxP system, we determined that the altered CD4+ T cell response to infection in developmentally exposed mice reflects a combination of intrinsic and extrinsic changes in CD4+ T cells, which are revealed in a tissue-specific manner. While the extrinsic factors triggered by developmental exposure that influence CD4+ T cell function later in life remain to be elucidated, we determined that these changes require live, replicating virus in the lung, suggesting a novel effect of developmental exposure on the structural cells of the lung. The implications of this work extend beyond influenza virus infection, as we observe changes in disease progression in developmentally exposed offspring in a CD4+ T cell dependent model of systemic autoimmunity. Together, this work establishes that CD4+ T cells are changed by activation of the AhR during development, and that these modifications have the potential to mediate the persistent alterations in immune responses observed in exposed human populations.

Subjects/Keywords: Aryl Hydrocarbon Receptor; CD4 T Cell; Developmental Exposure

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

APA (6^th Edition):

Boule , L. A. (2015). Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/30128

Chicago Manual of Style (16^th Edition):

Boule , Lisbeth A. “Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life.” 2015. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/30128.

MLA Handbook (7^th Edition):

Boule , Lisbeth A. “Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life.” 2015. Web. 04 Mar 2021.

Vancouver:

Boule LA. Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/30128.

Council of Science Editors:

Boule LA. Characterizing the Effects of Developmental Activation of the Aryl Hydrocarbon Receptor on CD4+ T Cell Responses Later in Life. [Doctoral Dissertation]. University of Rochester; 2015. Available from: http://hdl.handle.net/1802/30128

Penn State University

19. Girer, Nathaniel Gabriel. AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM.

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13610nug128

► The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor from the basic helix-loop-helix PER/ARNT/SIM family of proteins that is evolutionarily conserved in both vertebrates… (more)

▼ The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor from the basic helix-loop-helix PER/ARNT/SIM family of proteins that is evolutionarily conserved in both vertebrates and invertebrates. Known as a "promiscuous" receptor, AHR can bind to several different classes of chemical compounds such as polycyclic aromatic hydrocarbons (PAH) and flavonoids. When not bound to ligand, AHR resides in a cytosolic complex containing two molecules of heat shock protein 90, one molecule of X-associated protein 2, and a molecule of p23. Upon ligand binding, this complex is transported to the nucleus via nuclear importins and AHR dissociates to form a heterodimer with aryl hydrocarbon nuclear translocator (ARNT). The AHR/ARNT heterodimer then binds to specific DNA sequences known as dioxin response elements (DRE) within the promoter region of target genes (e.g. cytochrome P450 enzyme 1A1, CYP1A1) to activate their transcription. Previous studies have primarily examined AHR within the context of ligand-mediated transcriptional activation of its prototypical target gene, Cyp1a1. However, the AHR can also influence gene transcription in the absence of exogenous ligand and/or Cyp1a1 expression. Using a conditional AHR knockout mouse model that lacks hepatocyte-specific AHR expression (Ahrfx/fxAlbCre), this dissertation examines how basal AHR activity in the absence of Cyp1a1 transcription can influence metabolic homeostasis. In particular, the data reveal that the loss of hepatocyte-specific AHR expression correlates with reduced body and liver mass relative to congenic AHR-expressing mice (Ahrfx/fx). Additionally, Ahrfx/fxAlbCre mice maintained on purified AIN-93M diet display impaired glucose tolerance without any perturbations of insulin sensitivity. Conversely, Ahrfx/fxAlbCre mice challenged with a high-sucrose dietary modification of AIN-93M exhibit reduced insulin sensitivity without any difference in glucose tolerance. Most notably, Ahrfx/fxAlbCre mice challenged with a high-fat/high-sucrose (HF/HS) diet exhibit significantly decreased gene/protein expression of key enzymes involved in de novo fatty acid synthesis and fatty acid import, as well as significantly increased expression of key fatty acid export genes. Furthermore, inflammatory gene expression is also significantly reduced in HF/HS-fed Ahrfx/fxAlbCre mice relative to Ahrfx/fx. Together, the data suggest that basal hepatocyte-specific AHR signaling may promote diet-induced steatohepatitis in Ahrfx/fx mice. Utilizing the Ahrfx/fxAlbCre mouse model, this dissertation also explores the role of AHR in regulating hepatic fibroblast growth factor 21 (FGF21) production. FGF21 is an important metabolic hormone and regulator of the fasting response. Notably, FGF21 can attenuate obesity-associated morbidities when administered to various genetic and diet-induced mouse models of the disease. In the absence of exogenous AHR ligand, non-fasted Ahrfx/fxAlbCre mice exhibit 4-fold greater hepatic Fgf21 expression relative to Ahrfx/fx, along with elevated… Advisors/Committee Members: Gary Perdew, Dissertation Advisor/Co-Advisor, Gary Perdew, Committee Chair/Co-Chair, Andrew Patterson, Committee Member, Jeffrey Peters, Committee Member, Connie Rogers, Outside Member, Ross Hardison, Committee Member, Ross Hardison, Committee Member.

Subjects/Keywords: Aryl Hydrocarbon Receptor; Fibroblast growth factor 21; Liver Metabolism

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

APA (6^th Edition):

Girer, N. G. (2016). AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13610nug128

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):

Girer, Nathaniel Gabriel. “AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM.” 2016. Thesis, Penn State University. Accessed March 04, 2021. https://submit-etda.libraries.psu.edu/catalog/13610nug128.

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

MLA Handbook (7^th Edition):

Girer, Nathaniel Gabriel. “AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM.” 2016. Web. 04 Mar 2021.

Vancouver:

Girer NG. AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Mar 04]. Available from: https://submit-etda.libraries.psu.edu/catalog/13610nug128.

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

Council of Science Editors:

Girer NG. AN EXAMINATION OF THE ARYL HYDROCARBON RECEPTOR IN LIVER METABOLISM. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13610nug128

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

Penn State University

20. Hubbard, Troy David. Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor.

Degree: 2017, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13677tdh176

► The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor of the basic region helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) homology super family. The AHR was first identified… (more)

▼ The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor of the basic region helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) homology super family. The AHR was first identified as the primary mediator of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity and regulator of xenobiotic metabolism. Further investigation revealed AHR possesses a promiscuous ligand binding domain (LBD) that is able to bind to an array of exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs). Following ligand-binding, the AHR forms a functional heterodimeric transcription factor with AHR nuclear translocator (ARNT) and regulates expression of target genes via binding of dioxin response elements (DREs) within their promoters. The physiological activity of the AHR has expanded to include pivotal roles within immune regulation, mucosal barrier function, cell cycle progression, organogenesis, circadian rhythm, and cellular differentiation pathways. However, these functions often require the ligand activated form of the receptor and are known to occur in the absence of exogenous ligand. This finding led to the premise and eventual characterization of endogenous AHR ligands. The catabolism of the amino acid tryptophan by commensal microorganisms, endogenous enzymes, and radical oxidation is a known source of numerous AHR ligands. The studies presented in here build upon previously published data establishing microbial metabolism as a reservoir of endogenous ligand production. In our research we have identified the microbial tryptophan metabolite indole as a human AHR selective agonist through SAR studies and in silico modeling of AHR-ligand molecular docking. In silico molecular docking models support observations of differential indole responsiveness between species through a unique bi-molecular (2:1) binding stoichiometry that is sterically permissive within the human AHR, but not its mouse homolog. The capacity for host cells to sense microbial indole through the AHR may be paramount to the establishment of an inter-kingdom signaling pathway that affects maintenance of intestinal homeostasis. Molecular functionalities of the AHR, such as heterodimerization with ARNT and binding of DREs, are conserved among vertebrate and invertebrate species. However, ligand specificity of the AHR can vary between species. Comparative studies have shown that the human AHR displays reduced binding capacity with regard to prototypical PAH agonists when compared to rodent homologs. Such differences suggest that divergence of the AHR ligand binding domain (LBD) structure during the course of mammalian evolution facilitated interspecies variation in ligand selectivity. Here we present evidence supporting the hypothesis that selective desensitization of the human AHR to PAHs arose during speciation of Homo sapiens. Interspecies AHR analyses, through utilization of ligand binding assay, DNA binding assay, and AHR-dependent gene expression identified a single amino acid substitution (A381V)… Advisors/Committee Members: Dr. Gary Perdew, Dissertation Advisor/Co-Advisor, Dr. Andrew Patterson, Committee Chair/Co-Chair, Dr. Jeffrey Peters, Committee Member, Dr. Ming Tien, Committee Member, Dr. Edward Dudley, Outside Member.

Subjects/Keywords: aryl hydrocarbon receptor; AHR; Evolution; Ligand selectivity; PAHs; Toxicity

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

APA (6^th Edition):

Hubbard, T. D. (2017). Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13677tdh176

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):

Hubbard, Troy David. “Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor.” 2017. Thesis, Penn State University. Accessed March 04, 2021. https://submit-etda.libraries.psu.edu/catalog/13677tdh176.

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

MLA Handbook (7^th Edition):

Hubbard, Troy David. “Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor.” 2017. Web. 04 Mar 2021.

Vancouver:

Hubbard TD. Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor. [Internet] [Thesis]. Penn State University; 2017. [cited 2021 Mar 04]. Available from: https://submit-etda.libraries.psu.edu/catalog/13677tdh176.

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

Council of Science Editors:

Hubbard TD. Ligand Selectivity and Evolutionary Divergence of the Human Aryl Hydrocarbon Receptor. [Thesis]. Penn State University; 2017. Available from: https://submit-etda.libraries.psu.edu/catalog/13677tdh176

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

University of Waterloo

21. Wiseman, Steve. CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH.

Degree: 2007, University of Waterloo

URL: http://hdl.handle.net/10012/3234

► Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) are widespread in aquatic systems. These toxicants bioaccumulate in the tissues of aquatic organisms, especially fish as… (more)

▼ Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) are widespread in aquatic systems. These toxicants bioaccumulate in the tissues of aquatic organisms, especially fish as they occupy a position near the top of the aquatic food web. Teleost fish respond to stressors, including toxicants, by activating a co-ordinated network of adaptive responses, collectively termed the integrated stress response, which allows animals to regain homeostasis. Depending on the nature of the stressor, this stress response may be a generalised endocrine response that occurs at the organismal level and/or a cellular response involving protein synthesis. The cellular response to PCB insult involves aryl hydrocarbon receptor (AhR) activation and the induction of biotransformation enzymes, including cytochrome P4501A (Cyp1A). However, little is known about the mode of action of PCBs in affecting the adaptive stress response in animals. The objective of this thesis was to investigate the role played by AhR in mediating PCB impact on the highly conserved physiological responses to secondary stressors in fish. The experimental approach involved whole animal exposure studies with PCBs both in a laboratory setting as well as using feral fish. Also, in vitro mechanistic studies with pharmacological agents [AhR agonist (β-naphthoflavone) and antagonist (resveratrol), Hsp90 inhibitor (geldanamycin), proteasomal inhibitor (MG-132) and transcription (Actinomycin D) and translational inhibitors (cycloheximide D)] were carried out to understand AhR regulation in primary cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes. Also, a targeted trout cDNA microarray was developed as a tool to identify stress-responsive genes and signaling networks in fish. Short-term (3 day) exposure to PCBs, while inducing liver AhR and Cyp1A expression, did not modify the adaptive plasma cortisol response to an acute handling disturbance in rainbow trout. However, PCBs exposure did modify the metabolic response that is critical for recovery from an acute stressor in rainbow trout. To assess the impact of chronic PCB exposure on cellular stress response, two feral populations of Arctic char (Salvelinus alpinus) from Bjørnøya Island, Norway, were utilized. This is because the average PCB load in char liver from Lake Ellasjøen was approximately 25-fold higher than in individuals from Lake Øyangen, providing a natural setting to compare long-term toxicant impact on stress proteins. Liver Cyp1A expression was elevated in the high PCB fish suggesting AhR activation. Changes in mRNA abundance and/or protein expression of glucocorticoid receptor (GR), heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) in fish from the high PCB lake leads to the proposal that chronic exposures to PCBs is proteotoxic to the fish. In vitro mechanistic studies with trout hepatocytes revealed for the first time that AhR is autoregulated in response to ligand activation in rainbow trout. Furthermore this AhR regulation as well as AhR signaling…

Subjects/Keywords: Aryl Hydrocarbon Receptor; Stress Response

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

APA (6^th Edition):

Wiseman, S. (2007). CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/3234

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):

Wiseman, Steve. “CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH.” 2007. Thesis, University of Waterloo. Accessed March 04, 2021. http://hdl.handle.net/10012/3234.

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

MLA Handbook (7^th Edition):

Wiseman, Steve. “CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH.” 2007. Web. 04 Mar 2021.

Vancouver:

Wiseman S. CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH. [Internet] [Thesis]. University of Waterloo; 2007. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10012/3234.

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

Council of Science Editors:

Wiseman S. CHARACTERIZATION OF AHR SIGNALING AND THE IMPACT OF POLYCHLORINATED BIPHENYLS ON THE ADAPTIVE RESPONSES TO STRESS IN FISH. [Thesis]. University of Waterloo; 2007. Available from: http://hdl.handle.net/10012/3234

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

Boston University

22. Stanford, Elizabeth Ann. The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells.

Degree: PhD, Molecular and Translational Medicine, 2015, Boston University

URL: http://hdl.handle.net/2144/16211

► Self-renewing, chemoresistant cancer cells that contribute to cancer metastasis and patient relapse have properties similar to those of stem cells, and have been termed "cancer… (more)

▼ Self-renewing, chemoresistant cancer cells that contribute to cancer metastasis and patient relapse have properties similar to those of stem cells, and have been termed "cancer stem cells" (CSCs) in the literature. The identification of signaling pathways that regulate CSC development and/or function is an important step towards understanding why patients relapse, and towards development of novel therapeutics that specifically target CSC vulnerabilities. Recent studies have identified a role for the aryl hydrocarbon receptor (AHR), an environmental carcinogen receptor implicated in cancer initiation, in normal tissue-specific stem cell self-renewal. These studies inspired the hypothesis that the AHR plays a role in CSC development. To test this hypothesis, AHR activity in Hs578T triple negative and SUM149 inflammatory breast cancer cells was modulated with AHR ligands, shRNA, or AHR-specific inhibitors and their phenotypic, genomic, and functional CSC characteristics were evaluated. Aldehyde dehydrogenase (ALDH) was used as an epithelial stem cell marker for flow cytometry. Results demonstrate that: 1) ALDHhigh cells express elevated levels of Ahr and the AHR-driven gene that encodes cytochrome p450 isoform 1b1 (Cyp1b1), 2) AHR knockdown reduces ALDH activity, 3) AHR hyper-activation significantly increases ALDH1 activity, expression of stem cell- and invasion/migration-associated genes, and accelerates cell migration, 4) a highly significant correlation between Ahr or Cyp1b1 expression (as a surrogate marker for AHR activity) and expression of the CSC- and invasion/migration-associated gene sets was seen with genomic data obtained from 79 human breast cancer cell lines and over 1850 primary human breast cancers, 5) the AHR interacts directly with the transcription factors Sox2 and Runx1, and AHR ligands increase this interaction, 6) AHR knockdown inhibits tumorsphere formation in low adherence conditions, 7) AHR inhibition blocks the rapid migration of ALDHhigh cells and reduces ALDHhigh cell chemoresistance, and 8) AHR knockdown inhibits tumor growth and reduces tumor Aldh1a1, Sox2, and Cyp1b1 expression in orthotopic xenografts. These data suggest that the AHR plays an important role in development of CSCs in a large fraction of human breast cancers and that environmental AHR ligands may exacerbate breast cancer by enhancing expression of CSC-like properties.

Subjects/Keywords: Molecular biology; Aryl hydrocarbon receptor; Breast cancer; Cancer stem cells

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

APA (6^th Edition):

Stanford, E. A. (2015). The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/16211

Chicago Manual of Style (16^th Edition):

Stanford, Elizabeth Ann. “The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells.” 2015. Doctoral Dissertation, Boston University. Accessed March 04, 2021. http://hdl.handle.net/2144/16211.

MLA Handbook (7^th Edition):

Stanford, Elizabeth Ann. “The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells.” 2015. Web. 04 Mar 2021.

Vancouver:

Stanford EA. The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells. [Internet] [Doctoral dissertation]. Boston University; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2144/16211.

Council of Science Editors:

Stanford EA. The role of the aryl hydrocarbon receptor in the development of cells with molecular and functional characteristics of breast cancer stem cells. [Doctoral Dissertation]. Boston University; 2015. Available from: http://hdl.handle.net/2144/16211

University of Toronto

23. Cho, Tiffany Elizabeth. 3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice.

Degree: 2015, University of Toronto

URL: http://hdl.handle.net/1807/74562

►

The aryl hydrocarbon receptor (AHR) is a ligand-regulated transcription factor that is activated upon binding to various ligands. The activated AHR modulates the expression of… (more)

Subjects/Keywords: 3-Methylcholanthrene; Aryl Hydrocarbon Receptor; Chylous Ascites; Lethality; TIPARP; Toxicity; 0383

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

APA (6^th Edition):

Cho, T. E. (2015). 3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/74562

Chicago Manual of Style (16^th Edition):

Cho, Tiffany Elizabeth. “3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice.” 2015. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/74562.

MLA Handbook (7^th Edition):

Cho, Tiffany Elizabeth. “3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice.” 2015. Web. 04 Mar 2021.

Vancouver:

Cho TE. 3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/74562.

Council of Science Editors:

Cho TE. 3-Methylcholanthrene Induces Chylous Ascites and Lethality in Tiparp Knockout Mice. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/74562

University of Toronto

24. Powis, Melanie Lynn. Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals.

Degree: 2011, University of Toronto

URL: http://hdl.handle.net/1807/29602

►

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran and 2,3,7,8-tetrachlorodibenzofuran. Y322 is believed to play a… (more)

Subjects/Keywords: Aryl Hydrocarbon Receptor; Coactivators; Dioxin; Omeprazole; Furans; 0419

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APA (6^th Edition):

Powis, M. L. (2011). Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/29602

Chicago Manual of Style (16^th Edition):

Powis, Melanie Lynn. “Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals.” 2011. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/29602.

MLA Handbook (7^th Edition):

Powis, Melanie Lynn. “Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals.” 2011. Web. 04 Mar 2021.

Vancouver:

Powis ML. Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals. [Internet] [Masters thesis]. University of Toronto; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/29602.

Council of Science Editors:

Powis ML. Modulation of Aryl Hydrocarbon Receptor-dependent Transcription by Halogenated Compounds and Pharmaceuticals. [Masters Thesis]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/29602

University of Texas Southwestern Medical Center

25. D'Brot, Alejandro. Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations.

Degree: 2014, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/3311

► It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, determinants that specify… (more)

▼ It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. I show here that Tango7 genetically interacts with the apoptotic machinery but instead of regulating cell death, collaborates with the apoptosome to drive caspase-dependent cellular remodeling. Specifically, Tango7 is required for non-apoptotic caspase activity during spermatid remodeling and localizes to the active apoptosome compartment in these cells via its C terminus. Furthermore, Tango7 directly stimulates activity of reconstituted apoptosomes in vitro. These and other data presented here suggest that Tango7 physically recruits the apoptosome to specify this complex for nonapoptotic cellular remodeling. In vivo genetic model systems are powerful tools to deconstruct activity of genes driving human disease. The tumor suppressor p53 is mutated more than any other gene in human cancer, but unlike other tumor suppressors, it acquires missense mutations which encode oncogenic variants. These gain-of-function mutants promote more aggressive and metastatic cancers in vivo but their oncogenic activity is not well understood. To address this problem, I have exploited Drosophila as a platform to study and stratify human p53 (hp53) mutants. I replaced fly p53 with either wild-type hp53 or 5 of the most prevalent hp53 mutations in cancer. In this system, hp53 is under control of endogenous Dp53 regulatory elements and can regulate in vivo transcriptional activation and apoptosis like its fly counterpart. Furthermore, wild-type hp53 forms foci in the germline that localize to the same subnuclear compartment as Dp53 foci. This property is compromised in all of the gain-of-function mutants and can thus be used to distinguish oncogenic variants from wild-type hp53. Future studies aim at finding whether this and other properties shared among the 5 mutants can help stratify oncogenic p53 mutations found in human cancer. Advisors/Committee Members: Scaglioni, Pier Paolo, Shay, Jerry W., Yu, Hongtao.

Subjects/Keywords: Apoptosomes; Aryl Hydrocarbon Receptor Nuclear Translocator; Caspases; Drosophila melanogaster; Drosophila Proteins

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APA (6^th Edition):

D'Brot, A. (2014). Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/3311

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):

D'Brot, Alejandro. “Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed March 04, 2021. http://hdl.handle.net/2152.5/3311.

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

MLA Handbook (7^th Edition):

D'Brot, Alejandro. “Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations.” 2014. Web. 04 Mar 2021.

Vancouver:

D'Brot A. Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2152.5/3311.

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

Council of Science Editors:

D'Brot A. Of Apoptosomes and Oncogenes: Repurposing a Death Machine & Deconstructing the Action of P53 Mutations. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/3311

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

Queen Mary, University of London

26. Aflorei, Elena Daniela. Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo.

Degree: PhD, 2016, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12511 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775181

► A phenotypically distinct subgroup of familial isolated pituitary adenoma (FIPA) families has mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene leading to young-onset acromegaly… (more)

▼ A phenotypically distinct subgroup of familial isolated pituitary adenoma (FIPA) families has mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene leading to young-onset acromegaly in most patients. These patients typically develop invasive pituitary adenomas, but the mechanisms by which AIP inactivation promotes pituitary tumorigenesis and an aggressive behaviour remain unknown. To date, more than 70 different AIP variants have been reported and determining the pathogenicity of missense variants is a challenging problem. The Drosophila AIP orthologue (CG1847) is located on the X chromosome and encodes a protein of similar size and structure to human protein (hAIP). I have generated CG1847 deficient flies via two methods: in vivo RNAi knockdown and imprecise excision of a transposable P-element, which generated a putative null allele of CG1847. Our data show that knockdown and knockout of CG1847 results in lethality confirming that AIP is an essential gene. To reveal the potential underlying molecular mechanisms of loss of AIP, a whole transcriptome analysis was performed in mutant versus control male larvae. This allowed us to determine gene expression profiles and to identify key pathways that are significantly altered in the mutant, and that are related to embryonic development or survival. To functionally test the homology between hAIP and CG1847, I used the Gal4/UAS system to perform rescue experiments. I subsequently tested whether wild-type hAIP, a truncated hAIP and four missense mutations identified in FIPA families could rescue the lethality of CG1847exon1_3 mutants by expressing hAIP during fly development. In this thesis were identified novel AIP features. CG1847 is a Drosophila melanogaster AIP orthologue and is essential for normal development. RNA sequencing revealed possible new underlying CG1847 molecular mechanisms as the tumour suppressor function of AIP might involve the regulation of cytoskeletal organisation. Drosophila is a useful in vivo system to study human AIP missense variants to establish pathogenicity.

Subjects/Keywords: Pituitary adenoma; Aryl hydrocarbon receptor interacting protein gene

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

APA (6^th Edition):

Aflorei, E. D. (2016). Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/12511 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775181

Chicago Manual of Style (16^th Edition):

Aflorei, Elena Daniela. “Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo.” 2016. Doctoral Dissertation, Queen Mary, University of London. Accessed March 04, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/12511 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775181.

MLA Handbook (7^th Edition):

Aflorei, Elena Daniela. “Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo.” 2016. Web. 04 Mar 2021.

Vancouver:

Aflorei ED. Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2016. [cited 2021 Mar 04]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12511 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775181.

Council of Science Editors:

Aflorei ED. Application of a Drosophila melanogaster model to study Familial Isolated Pituitary Adenomas syndrome pathogenesis in vivo. [Doctoral Dissertation]. Queen Mary, University of London; 2016. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/12511 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775181

University of Illinois – Urbana-Champaign

27. Basavarajappa, Mallikarjuna. Mechanism of methoxychlor toxicity in mouse ovarian antral follicles.

Degree: PhD, 5274, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/29409

► 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor; MXC) is an organochlorine pesticide used against pests and insects that attack crops, gardens, vegetables, pets, and livestock. MXC targets the ovary and… (more)

▼ 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor; MXC) is an organochlorine pesticide used against pests and insects that attack crops, gardens, vegetables, pets, and livestock. MXC targets the ovary and its exposure has adverse effects on reproductive function in adult female mice causing persistent estrus, reduced fertility, and ovarian atrophy. MXC reduces fertility by increasing atresia of antral follicles and by decreasing numbers of healthy antral follicles in adult female mice. Further, MXC inhibits growth and induces atresia of mouse antral follicles in vitro. Little is known, however, about the mechanisms by which MXC causes slow growth and atresia of antral follicles. Hence, this dissertation work was designed to help us to better understand the mechanism of action of MXC in antral follicles by examining the effects of MXC on steroid levels, Bcl2 factors and caspase activity, and by determining if MXC exerts toxicity through an AHR pathway. Since MXC is known to target antral follicles, the major producer of sex steroids in the ovary, the present study first tested the hypothesis that MXC decreases estradiol (E2) levels by altering steroidogenic and metabolic enzymes in the antral follicles. Given that MXC induces atresia after long term exposure, in part, by increasing the pro-apoptotic factor Bax and decreasing the anti-apoptotic factor Bcl2 in antral follicles, the present study also tested the hypothesis that MXC induces atresia at early time points and alters other pro-apoptotic (Bok and Casp3) and anti-apoptotic factors (Bcl-xL) in addition to Bcl2 and Bax. In addition, the present study tested the hypothesis that MXC alters caspase activity in the follicles. Several studies indicate that many chemicals act through the aryl hydrocarbon receptor (AHR) pathway and one study has shown that MXC binds to the AHR in liver cells. Hence, the present work also tested the hypothesis that MXC binds to the AHR to inhibit follicle growth and induce atresia of antral follicles. To test these hypotheses, antral follicles were isolated from ovaries of female wild-type (WT) or AHR knock-out (AHRKO) mice and cultured with either vehicle (dimethylsulfoxide; DMSO) or MXC. Follicle growth was measured every 24 h for 96 or 168 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes, the E2 metabolic enzyme Cyp1b1, and Bcl2 related factors were measured using qPCR. Caspase activity and atresia were also measured in follicles. In granulosa cells, MXC binding to AHR was also measured using transfection experiments. The results indicate that MXC decreases most of steroidogenic enzymes, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. The results also indicate that, at 24 h, MXC increases Bax levels and does not affect Bcl2 levels. This increases the Bax/Bcl2 ratio, which in turn may increase the mitochondrial permeability leading to activation of caspase… Advisors/Committee Members: Flaws, Jodi A. (advisor), Hofmann, Marie-Claude (committee member), Dirikolu, Levent (committee member), Jeffery, Elizabeth H. (committee member), Nowak, Romana A. (committee member).

Subjects/Keywords: methoxychlor; antral follicles; ovary; mouse; aryl hydrocarbon receptor; atresia; growth

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

APA (6^th Edition):

Basavarajappa, M. (2012). Mechanism of methoxychlor toxicity in mouse ovarian antral follicles. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/29409

Chicago Manual of Style (16^th Edition):

Basavarajappa, Mallikarjuna. “Mechanism of methoxychlor toxicity in mouse ovarian antral follicles.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed March 04, 2021. http://hdl.handle.net/2142/29409.

MLA Handbook (7^th Edition):

Basavarajappa, Mallikarjuna. “Mechanism of methoxychlor toxicity in mouse ovarian antral follicles.” 2012. Web. 04 Mar 2021.

Vancouver:

Basavarajappa M. Mechanism of methoxychlor toxicity in mouse ovarian antral follicles. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2142/29409.

Council of Science Editors:

Basavarajappa M. Mechanism of methoxychlor toxicity in mouse ovarian antral follicles. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/29409

Duke University

28. Van Tiem, Lindsey Anne. Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) .

Degree: 2011, Duke University

URL: http://hdl.handle.net/10161/5705

► Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants formed from the incomplete combustion of fossil fuels and are found in the environment as complex… (more)

▼ Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants formed from the incomplete combustion of fossil fuels and are found in the environment as complex mixtures. PAHs are developmentally toxic to fish, causing yolk sac edema, hemorrhaging, craniofacial malformations and cardiac defects including impaired heart looping, elongated heart, decreased blood flow, and pericardial effusion. Previous research has shown that many of the toxic effects of PAHs are mediated through the aryl hydrocarbon receptor (AHR), which upregulates phase I and II metabolic genes, but the underlying mechanisms of PAH-induced toxicity are not yet known. The primary goal of this dissertation was to better understand the molecular mechanisms by which PAH mixtures cause developmental toxicity in fish. To this end, the zebrafish (Danio rerio) was used as a developmental model. Simple mixtures consisting of a PAH that is an AHR agonist (benzo[a]pyrene or benzo[k]fluoranthene) and a PAH that is a cytochrome P450 1 (CYP1) inhibitor (fluoranthene) were used in these experiments along with the dioxin-like compound 3,3',4,4',5-pentachlorobiphenyl (PCB-126). Morpholino gene knockdown was used to examine the role of specific genes in response to PAHs, gene expression changes in response to PAH exposures were examined via QPCR, quantification of pericardial effusion was used as a metric for cardiac toxicity, and CYP1 activity was measured as an indication of AHR pathway induction. First, PAH mixtures consisting of an AHR agonist (BkF) and a CYP1 inhibitor (FL) induced cardiac toxicity that was preceded by upregulation of CYP1 and redox-responsive gene expression, and these effects were dependent upon the AHR2. Second, knockdown of glutathione s-transferase pi class 2 (GSTp2), part of phase II metabolism, exacerbated PAH-induced toxicity but did not affect PCB-126-induced toxicity. Third, knockdown of another isoform of the AHR, AHR1, exacerbated PAH- and PCB-126-induced toxicity and increased CYP1 activity but did not affect CYP expression in response to these agonists. Simultaneous knockdown of AHR1A and AHR2 did not exacerbate nor ameliorate PAH-induced toxicity but did prevent PCB-126-induced toxicity. Fourth, to examine AHR2-dependent and AHR2-independent gene induction in zebrafish hearts in response to PAHs, microarrays were used. Gene expression changes caused by PAHs were largely AHR2-dependent and consisted of genes involved in cell adhesion, oxidation-reduction, and TGF-&beta signaling processes as well as genes involved in heart structure and function. These findings help to elucidate how PAHs elicit deformities during development and highlight differences between PAHs and other AHR agonists. Additionally, these experiments have identified other genes in addition to AHR2 that are involved in mediating or responding to the toxicity of PAHs. Advisors/Committee Members: Di Giulio, Richard T (advisor).

Subjects/Keywords: Toxicology; aryl hydrocarbon receptor; development; morpholino; polycyclic aromatic hydrocarbons; zebrafish

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APA (6^th Edition):

Van Tiem, L. A. (2011). Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/5705

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):

Van Tiem, Lindsey Anne. “Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) .” 2011. Thesis, Duke University. Accessed March 04, 2021. http://hdl.handle.net/10161/5705.

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

MLA Handbook (7^th Edition):

Van Tiem, Lindsey Anne. “Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) .” 2011. Web. 04 Mar 2021.

Vancouver:

Van Tiem LA. Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) . [Internet] [Thesis]. Duke University; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10161/5705.

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

Council of Science Editors:

Van Tiem LA. Molecular Mechanisms of Polycyclic Aromatic Hydrocarbon-induced Teratogenesis in Zebrafish (Danio rerio) . [Thesis]. Duke University; 2011. Available from: http://hdl.handle.net/10161/5705

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

Clemson University

29. Scobie, Micaela Ro. The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages.

Degree: PhD, Biological Sciences, 2019, Clemson University

URL: https://tigerprints.clemson.edu/all_dissertations/2491

► Glioblastoma Multiforme (GBM) is a highly invasive brain tumor that affects approximately 18,000 people annually in the USA alone yet remains without curative treatment.… (more)

▼ Glioblastoma Multiforme (GBM) is a highly invasive brain tumor that affects approximately 18,000 people annually in the USA alone yet remains without curative treatment. Median survival with treatment is 14 months, with most treatments only prolonging life for several months while causing severe adverse side effects. There is a need for new therapeutic modalities. Herein I explore two small molecules that show promise in modulating inflammatory signaling in an in vitro GBM model. Indirubins E804 (indirubin-3’-(2,3 dihydroxypropyl)-oximether) and 7BIO (7-Bromoindirubin-3’-oxime) are synthetic derivatives of natural indirubin. Natural indirubin is a bisindole alkaloid derived from tryptophan precursors and is an agonist for the ligand-activated transcription factor aryl hydrocarbon receptor (AHR). Indirubin has been shown to disrupt important cancer-driving signaling such as JAK/STAT3, GSK3, and CDKs. To determine AHR pathway significance in my results, I added a selective AHR antagonist, 6,2’,4’-trimethoxyflavone (TMF), in addition to indirubins. Herein I show that E804 modulates a large array of inflammatory genes, including down-regulation of important autocrine GBM signaling molecules like IL-6 and VEGF, which help drive tumor development. 7BIO, but not E804, increased the expression of STAT3, suggesting that this compound is not suitable for glioma therapy. Additional studies showed that E804 does not fully activate the unfolded protein response (UPR). The UPR is an ER stress pathway that can induce indiscriminate apoptosis - an undesirable side effect in an area as sensitive as the brain. Finally, using transcriptomics combined with pathway analysis, I examined the effects that E804- or E804+TMF-treated glioblastoma cells have on differentiated THP-1 macrophages to model the effects that gliomas may have on glioma-associated macrophages. Glioma-associated macrophages can comprise up to 30% of GBM mass, and, if activated by certain glioma-derived signals, have been implicated in tumor promotion. I found that treated-GBM supernatants inhibited gene profiles in THP-1 macrophages that are linked to tumor progression, such as the Wnt, TLR, and Cell Cycle pathways; enriched gene ontology (GO) terms in up-regulated gene lists involving vascularization and hormone metabolism; and modulated expression of genes associated with macrophage polarization. Taken together, the results of this study demonstrate that E804 and E804 + TMF modulate signaling in GBM cells, with the ability to influence macrophages. These treatments hold promise as an alternative to current modalities using very toxic nitrosourea compounds, and future work should continue to investigate crosstalk between macrophages and GBM, both in vitro and in vivo. Advisors/Committee Members: Charles D Rice, Vincent S Gallicchio, Vincent P Richards, Yanzhang Wei.

Subjects/Keywords: Aryl hydrocarbon receptor; E804; Glioblastoma Multiforme; Indirubin; Inflammation; Tumor associated macrophage

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

APA (6^th Edition):

Scobie, M. R. (2019). The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages. (Doctoral Dissertation). Clemson University. Retrieved from https://tigerprints.clemson.edu/all_dissertations/2491

Chicago Manual of Style (16^th Edition):

Scobie, Micaela Ro. “The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages.” 2019. Doctoral Dissertation, Clemson University. Accessed March 04, 2021. https://tigerprints.clemson.edu/all_dissertations/2491.

MLA Handbook (7^th Edition):

Scobie, Micaela Ro. “The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages.” 2019. Web. 04 Mar 2021.

Vancouver:

Scobie MR. The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages. [Internet] [Doctoral dissertation]. Clemson University; 2019. [cited 2021 Mar 04]. Available from: https://tigerprints.clemson.edu/all_dissertations/2491.

Council of Science Editors:

Scobie MR. The Effects of Indirubin Derivative E804 on Inflammatory Profiles in Glioblastoma Multiforme Cell Lines and Subsequent Crosstalk Effect on Tumor Associated THP-1 Macrophages. [Doctoral Dissertation]. Clemson University; 2019. Available from: https://tigerprints.clemson.edu/all_dissertations/2491

University of Montana

30. Kreitinger, Joanna Michelle. CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES.

Degree: PhD, 2018, University of Montana

URL: https://scholarworks.umt.edu/etd/11302

► The Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor best known for its role in xenobiotic metabolism of environmental pollutants. Activation of the… (more)

▼ The Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor best known for its role in xenobiotic metabolism of environmental pollutants. Activation of the AhR by its prototypical ligand 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) leads to pronounced thymic atrophy and severe immunosuppression. Studies of AhR activation can have dual applications: to better understand AhR-mediated immunotoxicity and to harness its immunomodulatory effects for therapeutic use. Here, we first aimed to determine whether AhR-mediated thymic atrophy was ligand-dependent through the use of dietary and endogenously sourced ligands, indole-3-carbinol (I3C) and 2-(19 H-indole-39 -carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) respectively. We also aimed to identify key mediators of TCDD-induced thymic atrophy through the use of lineage-specific Cre-lox conditional knockout mice. We hypothesized that AhR activation induces thymic atrophy in a ligand-dependent manner and AhR expression within CD11c+ DCs is necessary for thymic atrophy by TCDD. In vivo exposure of ITE and I3C yielded dramatically different thymic outcomes with ITE resulting in severe thymic atrophy similar to TCDD while I3C did not induce atrophy. Through the use of Cre-Lox conditional knockout mice under lineage-specific promoters, we identified a requisite role for AhR activation in CD11c+ cells for TCDD-induced thymic atrophy. We next aimed to apply current understanding of AhR-mediated immune suppression in the development of a liposomal nanoparticle (LNP) delivery system for concentrated delivery of AhR-agonist, ITE, to dendritic cells. Dendritic cells are exquisitely sensitive to AhR activation and promote the generation of regulatory T cells. ITE is a potent inducer of AhR activation; however, it is rapidly metabolized and systemic exposure to high doses can have undesirable effects. Therefore, we hypothesized that the generation and delivery of AhR agonist-loaded liposomal nanoparticles would activate the AhR in dendritic cells leading to a phenotype similar to TCDD, and result in cell-specific uptake when administered in vivo. LNP maintained high ITE entrapment, were of optimal size for dendritic cell uptake, induced AhR-responsive genes in vitro, and were preferentially taken up by splenic APCs. Together, this work furthers our understanding of AhR-mediated thymic atrophy, and presents a novel AhR agonist delivery system for therapeutic application of the AhR.

Subjects/Keywords: Aryl hydrocarbon Receptor; Dendritic cells; drug delivery; nanoparticles; Thymus

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

APA (6^th Edition):

Kreitinger, J. M. (2018). CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES. (Doctoral Dissertation). University of Montana. Retrieved from https://scholarworks.umt.edu/etd/11302

Chicago Manual of Style (16^th Edition):

Kreitinger, Joanna Michelle. “CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES.” 2018. Doctoral Dissertation, University of Montana. Accessed March 04, 2021. https://scholarworks.umt.edu/etd/11302.

MLA Handbook (7^th Edition):

Kreitinger, Joanna Michelle. “CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES.” 2018. Web. 04 Mar 2021.

Vancouver:

Kreitinger JM. CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES. [Internet] [Doctoral dissertation]. University of Montana; 2018. [cited 2021 Mar 04]. Available from: https://scholarworks.umt.edu/etd/11302.

Council of Science Editors:

Kreitinger JM. CONSEQUENCES OF ARYL HYDROCARBON RECEPTOR ACTIVATION: THYMIC ATROPHY AND THERAPEUTIC LIPOSOMAL NANOPARTICLES. [Doctoral Dissertation]. University of Montana; 2018. Available from: https://scholarworks.umt.edu/etd/11302

Open Access Theses and Dissertations