The methylmercury-L-cysteine conjugate is a substrate for the L-type large neutral amino acid transporter

Zhaobao Yin, Haiyan Jiang, Tore Syversen, João B.T. Rocha, Marcelo Farina, Michael Aschner

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Methylmercury (MeHg) is a potent neurotoxin. The mechanism(s) that governs MeHg transport across the blood-brain barrier and other biological membranes remains unclear. This study addressed the role of the L-type large neutral amino acid transporter, LAT1, in MeHg transport. Studies were carried out in CHO-k1 cells. Over-expression of LAT1 in these cells was associated with enhanced uptake of [14C]-MeHg when treated with l-cysteine, but not with the d-cysteine conjugate. In the presence of excess l-methionine, a substrate for LAT1, l-cysteine-conjugated [14C]-MeHg uptake was significantly attenuated. Treatment of LAT-1 over-expressing CHO-k1 cells with l-cysteine-conjugated MeHg was also associated with increased leakage of lactate dehydrogenase into the media as well as reduced cell viability measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. In contrast, knock-down of LAT1 decreased the uptake of l-cysteine-conjugated MeHg and attenuated the effects of MeHg on lactate dehydrogenase leakage and CHO-k1 cell viability. These results indicate that the MeHg-l-cysteine conjugate is a substrate for the neutral amino acid transporter, LAT1, which actively transports MeHg across membranes.

Original languageEnglish (US)
Pages (from-to)1083-1090
Number of pages8
JournalJournal of Neurochemistry
Volume107
Issue number4
DOIs
StatePublished - Nov 2008

Keywords

  • Amino acid transport
  • L-type large neutral amino acid transporter
  • Methylmercury
  • Neurotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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