L-lactate inhibits L-cystine/L-glutamate exchange transport and decreases glutathione content in rat cultured astrocytes

Abstract

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.