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L‐lactate inhibits L‐cystine/L‐glutamate exchange transport and decreases glutathione content in rat cultured astrocytes
Author(s) -
Koyama Yutaka,
Kimura Yuji,
Hashimoto Hitoshi,
Matsuda Toshio,
Baba Akemichi
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000301)59:5<685::aid-jnr12>3.0.co;2-z
Subject(s) - glutathione , cystine , glutamate receptor , chemistry , extracellular , glutathione disulfide , astrocyte , biochemistry , propionate , lactate dehydrogenase , metabolism , medicine , endocrinology , biology , cysteine , enzyme , central nervous system , receptor
In several brain pathologies, the level of brain L‐lactate increases. The stimulation of L‐lactate production is a detrimental factor in promoting neuronal cell damage and astrocytic dysfunction. Astrocytic glutathione metabolism has an important role to protect brain cells against oxidative stress. In this study, effects of L‐lactate on L‐cystine uptake and glutathione level in rat‐cultured astrocytes were examined. L‐Lactate decreased the L‐ 35 S‐cystine and Na + ‐independent L‐ 3 H‐glutamate uptakes into astrocytes at the concentrations more than 2.5 mM. The L‐lactate‐induced decrease in L‐ 35 S‐cystine uptake was neither affected by modification of extracellular pH nor mimicked by acetate, propionate and butyrate. The apparent Km value of the L‐ 35 S‐cystine uptake was increased by L‐lactate, while the Vmax was not changed. Astrocytic glutathione and nonprotein thiol content was decreased by incubation with 20 mM L‐lactate for 48 hours (65% and 75% of control values, respectively). The decreases in astrocytic glutathione and nonprotein thiol content were restored to normal levels by withdrawal of L‐lactate. These results suggest that L‐lactate inhibits astrocytic L‐cystine/L‐glutamate exchangers and affects the glutathione contents. J. Neurosci. Res. 59:685–691, 2000 © 2000 Wiley‐Liss, Inc.