Hormetic effect of methylmercury on Caenorhabditis elegans

Kirsten J. Helmcke, Michael Aschner

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalToxicology and Applied Pharmacology
Volume248
Issue number2
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Hormesis
Caenorhabditis elegans
Toxicity
Heat-Shock Proteins
Animals
Biological Models
Metallothionein
Poisons
Glutathione
Fluorescence
Phenotype
Research

Keywords

  • Caenorhabditis elegans
  • Hormesis
  • Methylmercury

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

Cite this

Hormetic effect of methylmercury on Caenorhabditis elegans. / Helmcke, Kirsten J.; Aschner, Michael.

In: Toxicology and Applied Pharmacology, Vol. 248, No. 2, 10.2010, p. 156-164.

Research output: Contribution to journalArticle

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