The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’?

<jats:title>Abstract</jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2</jats:sub>S) is a well‐known cytotoxic gas. Recently it has been shown to stimulate <jats:italic>N</jats:italic>‐methyl‐<jats:sc>d</jats:sc>‐aspartate (NMDA) receptors to enhance long‐term potentiation suggesting a novel neuromodulatory role <jats:italic>in vivo.</jats:italic> Endogenous levels of H<jats:sub>2</jats:sub>S in the brain are reported to range between 10 and 160 µ<jats:sc>m</jats:sc>. Considerably lower H<jats:sub>2</jats:sub>S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H<jats:sub>2</jats:sub>S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H<jats:sub>2</jats:sub>S ‘donor’, sodium hydrogen sulfide (NaSH) on peroxynitrite‐mediated damage to biomolecules and to cultured human SH‐SY5Y cells. H<jats:sub>2</jats:sub>S significantly inhibited peroxynitrite‐mediated tyrosine nitration and inactivation of α<jats:sub>1</jats:sub>‐antiproteinase to a similar extent to reduced glutathione at each concentration tested (30–250 µ<jats:sc>m</jats:sc>). H<jats:sub>2</jats:sub>S also inhibited peroxynitrite‐induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH‐SY5Y cells. These data suggest that H<jats:sub>2</jats:sub>S has the potential to act as an inhibitor of peroxynitrite‐mediated processes <jats:italic>in vivo</jats:italic> and that the potential antioxidant action of H<jats:sub>2</jats:sub>S deserves further study, given that extracellular GSH levels in the brain are very low.</jats:p>