Methylmercury (MeHg), a known neurotoxicant, is found in seafood, leading to regular exposure of humans to this compound. Many of the molecular targets and detoxifying components of MeHg toxicity, including glutathione (GSH), metallothioneins (MTs), and heat shock proteins (HSPs) have been identified; however, the molecular mechanisms of MeHg neurotoxicity are largely unknown. We used the model organism, Caenorhabditis elegans, to elucidate some of these mechanisms. We found that, although MeHg accumulated within C. elegans and caused a delay in development and a decrease in pharyngeal pumping rate, many endpoints, including life span, brood size, thrashing rate, and, most surprisingly, nervous system morphology, were unaffected. This finding led to the hypothesis that C. elegans has unique mechanisms for protecting its nervous system from MeHg neurotoxicity. We examined the involvement of GSH, MTs, and HSPs in MeHg toxicity in C. elegans and found that GSH levels were altered upon MeHg exposure, a glutathione s-transferase was highly upregulated upon exposure, and that the lack of MTs in MT knockout animals resulted in increased sensitivity to this toxicant. We also demonstrated that MeHg can induce hormesis in C. elegans, likely at least partially due to the involvement of GSTs in MeHg toxicity. As a result of our findings, we began to elucidate some of the molecular mechanisms of MeHg neuroprotection in the C. elegans model system. Our findings are highly valuable to the field of human health due to the regular exposure of humans to MeHg.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-01142010-160908 |
| Date | 18 January 2010 |
| Creators | Helmcke, Kirsten Jeanne |
| Contributors | Michael Aschner, David Miller, Ariel Deutch, Eugenia Gurevich, BethAnn McLaughlin |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-01142010-160908/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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