L-lactate inhibits L-cystine/L-glutamate exchange transport and decreases glutathione content in rat cultured astrocytes.
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.
Koyama
Y
Y
Molecular Neuropharmacology Laboratory, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Kimura
Y
Y
Hashimoto
H
H
Matsuda
T
T
Baba
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D003553:Cystine / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000037:antagonists & inhibitors*; D019344:Lactic Acid / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013438:Sulfhydryl Compounds / Q000037:antagonists & inhibitors
D002352:Carrier Proteins; D013438:Sulfhydryl Compounds; D019344:Lactic Acid; D003553:Cystine; D005978:Glutathione