title: Early-life exposure to methylmercury in wildtype and pdr-1/parkin knockout C. elegans.
abstract: We examined the impact of early-life exposure to methylmercury (MeHg) on Caenorhabditis elegans (C. elegans) pdr-1 mutants, addressing gene-environment interactions. We tested the hypothesis that early-life exposure to MeHg and knockout (KO) of pdr-1 (mammalian: parkin/PARK2) exacerbates MeHg toxicity and damage to the dopaminergic (DAergic) system. pdr-1KO worms showed increased lethality and decreased lifespan following MeHg exposure. Mercury (Hg) content, measured with inductively coupled plasma-mass spectrometry was increased in pdr-1KO worms compared to wildtype (N2) controls. 2'7' dichlorodihydrofluorescein diacetate assay revealed a significant increase in reactive oxygen species in both strains following MeHg exposure; however, while N2 worms showed an increase in skn-1 transcript levels following MeHg exposure, there was no difference in skn-1 induction in pdr-1KO worms. Dopamine-dependent behavioral analysis revealed an effect of MeHg on N2 wildtype worms, but no effect on pdr-1KO worms. Taken together, these results suggest that pdr-1KO worms are more sensitive to MeHg than wildtype worms, but MeHg does not exacerbate behavioral changes related to the absence of pdr-1.
authors.affiliation: Division of Pediatric Toxicology, Vanderbilt University Medical Center, 11425 MRB IV, 2215-B Garland Ave., Nashville, TN, 37232-0414, USA. ebany.martinez.finley@vanderbilt.edu
authors.forename: Ebany J
authors.initials: EJ
authors.lastname: Martinez-Finley
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D004781:Environmental Exposure; D013058:Mass Spectrometry; D008767:Methylmercury Compounds / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein