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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 γ‐ 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.