Hydrogen sulfide protects neurons from oxidative stress.

Hydrogen sulfide (H2S), which is a well-known toxic gas, is found in relatively high concentrations in the brain. Although a neuromodulatory role of H2S has been demonstrated, little is known of its other biological functions. Here we show that H2S protects primary cultures of neurons from death in a well-studied model of oxidative stress caused by glutamate, a process called oxidative glutamate toxicity--or oxytosis. We found that H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of gamma-glutamylcysteine synthetase and up-regulating cystine transport. Cystine (cysteine) is the rate-limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione.