Dokument: The role of the C. elegans Aryl hydrocarbon receptor in environmentally-driven aging
| Titel: | The role of the C. elegans Aryl hydrocarbon receptor in environmentally-driven aging | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=50945 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20190923-102833-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Brinkmann, Vanessa [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Esser, Charlotte [Gutachter] Prof. Dr. Martin, William [Gutachter] Dr. Ventura, Natascia [Betreuer/Doktorvater] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Aging is the highest risk factor for death and disease, and it is concurrently shaped by extrinsic and intrinsic factors. It is of great importance to understand the molecular mechanisms underlying these factors to prevent aging-associated diseases. In mammals, the hazardous effects of many environmental toxicants are mediated by the aryl-hydrocarbon receptor (AhR). The AhR is a highly conserved transcription factor of the bHLH/PAS protein family, which is activated through the binding of specific classes of ligands in mammals. Both, chemicals of anthropogenic origin (xenobiotics) and natural compounds were identified as AhR modulators. Specifically, AhR modulators can be divided into four classes: environmental, dietary, host-mediated, and microbial factors.
In C. elegans, the well-known AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin does not bind the AhR homolog AHR-1 and no other AHR-1 modulating compounds had been identified to date. Also, besides xenobiotic ligands, no other potential modulators of AHR-1 signaling have been tested for their ability to influence C. elegans life traits through AHR-1. Therefore, in this study, I addressed the question whether the C. elegans AHR-1 responds to any of the known classes of mammalian AhR modulators (either as ligands or ligand-independent) and whether AHR-1 influences the aging process. I specifically looked for health-associated parameters and gene expression in response to representatives of the four different classes. The environmental pollutant benzo(a)pyrene affected health and cyp (Cytochrome P450 monooxygenase) expression mainly independent of AHR-1. As a host-mediated factor, I used UVB, which produces a highly potent AhR ligand in vivo. I found that ahr-1 mutants are more sensitive against the UVB-induced reduction of fertility and that apoptosis is induced in ahr-1 mutants, while there was no significant induction of cyps. The dietary factor curcumin increased health and induced gene expression in an AHR-1-dependent manner. As microbial factors, I used different E. coli diets (HT115 vs. OP50), which I found to differentially impact on the health span of the ahr-1 C. elegans mutant. While assessing the function of AHR-1 in age-associated neurodegenerative diseases, I found that AHR-1 has an impact on the progression of polyglutamine aggregation. In conclusion, I showed that C. elegans is a good model for studying conserved AhR functions since it appears to be involved in the response to three out of four classes of mammalian AhR modulators. Moreover, AHR-1 affects aging and age-associated diseases. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie | |||||||
| Dokument erstellt am: | 23.09.2019 | |||||||
| Dateien geändert am: | 23.09.2019 | |||||||
| Promotionsantrag am: | 24.07.2018 | |||||||
| Datum der Promotion: | 24.09.2018 |
