TY - JOUR
T1 - Involvement of AAT transporters in methylmercury toxicity in Caenorhabditis elegans
AU - Caito, Samuel W.
AU - Zhang, Yaofang
AU - Aschner, Michael
N1 - Funding Information:
This work was funded by NIEHS R01 ES007331 and S10 RR026742 .
PY - 2013/6/14
Y1 - 2013/6/14
N2 - 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.
AB - 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.
KW - L-type large neutral amino acid transporter
KW - Methylmercury
KW - Molecular mimicry
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U2 - 10.1016/j.bbrc.2013.04.090
DO - 10.1016/j.bbrc.2013.04.090
M3 - Article
C2 - 23669041
AN - SCOPUS:84878992118
SN - 0006-291X
VL - 435
SP - 546
EP - 550
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -