title: Involvement of AAT transporters in methylmercury toxicity in Caenorhabditis elegans.
abstract: Methylmercury (MeHg) is a potent neurotoxin that enters mammalian cells as a conjugate with L-cysteine through L-type large neutral amino acid transporter, LAT1, by a molecular mimicry mechanism by structurally resembling L-methionine. Caenorhabditis elegans (C. elegans) has been increasingly used to study the neurotoxic effects of MeHg, but little is known about uptake and transport of MeHg in the worm. This study examined whether MeHg uptake through LAT1 is evolutionarily conserved in nematodes. MeHg toxicity in C. elegans was blocked by pre-treatment of worms with l-methionine, suggesting a role for amino acid transporters in MeHg transport. Knockdown of aat-1, aat-2, and aat-3, worm homologues to LAT1, increased the survival of C. elegans following MeHg treatment and significantly attenuated MeHg content following exposure. These results indicate that MeHg is transported in the worm by a conserved mechanism dependent on functioning amino acid transporters.
authors.affiliation: Division of Clinical Pharmacology and Pediatric Toxicology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-0414, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Caito
authors.forename: Yaofang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*; D015996:Survival Rate
chemical_list: D026905:Amino Acid Transport Systems; D008767:Methylmercury Compounds