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

J Neurochem. 2008 Nov;107(4):1083-90. doi: 10.1111/j.1471-4159.2008.05683.x. Epub 2008 Sep 13.


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 [(14)C]-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 [(14)C]-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • CHO Cells
  • Carbon Isotopes / metabolism
  • Cell Survival / drug effects
  • Cricetinae
  • Cricetulus
  • Cysteine / metabolism*
  • Cysteine / pharmacology
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Large Neutral Amino Acid-Transporter 1 / genetics
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Methylmercury Compounds / metabolism*
  • Methylmercury Compounds / pharmacology
  • RNA, Small Interfering / pharmacology
  • Tetrazolium Salts
  • Thiazoles
  • Transfection / methods


  • Carbon Isotopes
  • Large Neutral Amino Acid-Transporter 1
  • Methylmercury Compounds
  • RNA, Small Interfering
  • Tetrazolium Salts
  • Thiazoles
  • L-Lactate Dehydrogenase
  • thiazolyl blue
  • Cysteine