Hydrogen Sulfide Increases Glutathione Production and Suppresses Oxidative Stress in Mitochondria

Hydrogen sulfide (H(2)S) is a synaptic modulator as well as a neuroprotectant in the brain. We recently showed that H(2)S protects neurons from oxidative stress by increasing the levels of glutathione (GSH), a major cellular antioxidant, by more than twice that of a control through enhancing the cystine transport. Here we show that H(2)S enhances the transport of cysteine to increase GSH production more than cystine transport and to redistribute the localization of GSH to mitochondria. The efficiency of GSH production enhanced by H(2)S is even greater by fourfold under oxidative stress by glutamate. H(2)S reinstated GSH levels in the fetal brain decreased by ischemia/reperfusion in utero. In addition, Neuro2a…