Hydrogen Sulfide-Mediated Cellular Signaling and Cytoprotection

Abstract

Hydrogen sulfide (H2S) is a signaling molecule in the nervous and vascular systems. It also protects various organs from oxidative stress or ischemia-reperfusion injury. H2S is produced from L-cysteine by cystathionine β-synthase (CBS), cystathionine γ–lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT). We recently found that H2S is also produced from D-cysteine by 3MST along with D-amino acid oxidase (DAO). This pathway is mainly localized to in the cerebellum and the kidney, producing H2S more efficiently than the pathways that utilize L-cysteine as a substrate. The administration of D-cysteine to mice ameliorates renal ischemia-reperfusion injury more effectively than that of L-cysteine, promising a therapeutic application of D-cysteine to renal diseases. We recently found that H2S-derived polysulfides exist in the brain and induce Ca2+ influx by activating transient receptor potential ankyrin-1 (TRPA1) channels approximately 300 times more efficiently than H2S in astrocytes, which surround neuronal synapses and modulate their activity. Polysulfides are possible H2S-derived signaling molecules. This review focuses on the production of H2S from D-cysteine and polysulfides as possible signaling molecules derived from H2S.