Signaling by hydrogen sulfide (H2S) and polysulfides (H2Sn) in the central nervous system

Abstract

Hydrogen sulfide (H₂S) is a signaling molecule used to modify neuronal transmission, regulate vascular tone, protect tissues from oxidative stress, sense oxygen, and generate ATP. Hydrogen polysulfides (H₂S_n) have recently been identified as signaling molecules that mediate the activation of ion channels, regulation of tumor growth, and the transcriptional regulation of oxidative stress; some of which were previously ascribed to H₂S. Cystathionine β-synthetase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are known as H₂S-producing enzymes. 3MST also produces H₂S_n and other persulfurated molecules such as cysteine persulfide, glutathione persulfide, and persulfurated proteins. The chemical interaction of H₂S and nitric oxide (NO) also produces H₂S_n, which may be the mechanism underlying the synergistic effect of H₂S and NO that was initially reported on vascular relaxation. H₂S_n and other persulfurated molecules elicit their effect via S-sulfuration (S-sulfhydration) of specific cysteine residues of the target proteins. This review article focuses on the production and roles of H₂S_n as well as H₂S in the central nervous system.