Hormetic effect of methylmercury on Caenorhabditis elegans.
Research has demonstrated the toxic effects of methylmercury (MeHg), yet molecular mechanisms underlying its toxicity are not completely understood. Caenorhabditis elegans (C. elegans) offers a unique biological model to explore mechanisms of MeHg toxicity given many advantages associated with its ease of use and genetic power. Since our previous work indicated neurotoxic resistance of C. elegans to MeHg, the present study was designed to examine molecular mechanisms associated with this resistance. We hypothesized MeHg would induce expression of gst, hsp or mtl in vivo since glutathione (GSH), heat shock proteins (HSPs), and metallothioneins (MTs) have shown involvement in MeHg toxicity. Our studies demonstrated a modest, but significant increase in fluorescence in gst-4::GFP and mtl-1::GFP strains at an acute, low L1 MeHg exposure, whereas chronic L4 MeHg exposure induced expression of gst-4::GFP and hsp-4::GFP. Knockout gst-4 animals showed no alterations in lethality sensitivity compared to wildtype animals whereas mtl knockouts displayed increased sensitivity to MeHg exposure. GSH levels were increased by acute MeHg treatment and depleted with chronic exposure. We also demonstrate that MeHg induces hormesis, a phenotype whereby a sublethal exposure to MeHg rendered C. elegans resistant to subsequent exposure to the organometal. The involvement of gst-4, hsp-4, mtl-1, and mtl-2 in hormesis was examined. An increase in gst-4::GFP expression after a low-dose acute exposure to MeHg indicated that gst-4 may be involved in this response. Our results implicate GSH, HSPs, and MTs in protecting C. elegans from MeHg toxicity and show a potential role of gst-4 in MeHg-induced hormesis.
Helmcke
Kirsten J
KJ
Pharmacology Department and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37232, USA. Kirsten.J.Helmcke@gmail.com
Aschner
Michael
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008628:Mercury / Q000378:metabolism; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D008767:Methylmercury Compounds; D014874:Water Pollutants, Chemical; D008628:Mercury; D005978:Glutathione