Journal of Neural Transmission

, Volume 110, Issue 12, pp 1337–1348

Role of neuronal glutamate transporter in the cysteine uptake and intracellular glutathione levels in cultured cortical neurons

  • T. Himi
  • M. Ikeda
  • T. Yasuhara
  • M. Nishida
  • I. Morita

DOI: 10.1007/s00702-003-0049-z

Cite this article as:
Himi, T., Ikeda, M., Yasuhara, T. et al. J Neural Transm (2003) 110: 1337. doi:10.1007/s00702-003-0049-z

Summary.

Cysteine uptake is the rate-limiting process in glutathione synthesis. Previously we have shown that the inhibitors of excitatory amino acid transporters (EAATs) significantly enhance glutamate toxicity via depletion of intracellular glutathione. In this study we show evidence that the neuronal glutamate transporter EAAT3 is directly enrolled in cysteine uptake in cultured neurons. Neuronal cysteine uptake was dependent on the extracellular sodium, and was suppressed by EAAT inhibitors. Cysteine uptake was suppressed by extracellular glutamate and aspartate, substrates of EAATs, and not by substrates of cysteine transporters. Intracellular glutathione levels were reduced by EAAT inhibitors, and not by inhibitors of cysteine transporters. Knock down of EAAT3 expression using antisense oligonucleotide significantly reduced cysteine uptake, intracellular glutathione level, and neuronal viability against oxidative stress. These facts indicate that EAAT3 functions as a cysteine transporter, and this function seems to be unique and distinct from cysteine transporters that have been reported.

Keywords: Glutathione, reactive oxygen species, cysteine transport. 

Copyright information

© Springer-Verlag/Wien 2003

Authors and Affiliations

  • T. Himi
    • 1
  • M. Ikeda
    • 2
  • T. Yasuhara
    • 3
  • M. Nishida
    • 4
  • I. Morita
    • 1
  1. 1.Section of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, TokyoJP
  2. 2.Department of Clinical Research, National Saigata Hospital, NiigataJP
  3. 3.Department of Nutrition, Junior College of Tokyo University of Agriculture, Tokyo University of Agriculture, Setagaya-ku, TokyoJP
  4. 4.Trauma and Critical Care Center, Teikyo University School of Medicine, Itabashi-ku, Tokyo, JapanJP

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