Hydrogen sulfide protects astrocytes against H2O2-induced neural injury via enhancing glutamate uptake

Excess extracellular glutamate, the main excitatory neurotransmitter, may result in excitotoxicity and neural injury. The present study was designed to study the effect of hydrogen sulfide (H2S), a novel neuromodulator, on hydrogen peroxide (H2O2) -induced glutamate uptake impairment and cellular injuries in primary cultured rat cortical astrocytes. We found that NaHS (an H2S donor, 0.1-1000 μM) reversed H2O2-induced cellular injury in a concentration-dependent manner. This effect was attenuated by L-trans-pyrrolidine-2,4-dicarboxylic (PDC), a specific glutamate uptake inhibitor. Moreover, NaHS significantly increased [3H]glutamate transport in astrocytes treated with H2O2, suggesting that H2S may protect astrocytes via enhancing glutamate uptake function. NaHS also reversed H2O2-impaired glutathione (GSH) production. Blockade of glutamate uptake with PDC attenuated this effect, indicating that the effect of H2S on GSH production is secondary to the stimulation of glutamate uptake. In addition, it was also found that H2S may promote glutamate uptake activity via decreasing ROS generation, enhancing ATP production and suppressing ERK1/2 activation. In conclusion, our findings provide direct evidence that H2S has potential therapeutic value for oxidative stress-induced brain damage via a mechanism involving enhancing glutamate uptake function.