Hydrogen sulfide and polysulfides as signaling molecules

Abstract

Hydrogen sulfide (H₂S) is a familiar toxic gas that smells of rotten eggs. After the identification of endogenous H₂S in the mammalian brain two decades ago, studies of this molecule uncovered physiological roles in processes such as neuromodulation, vascular tone regulation, cytoprotection against oxidative stress, angiogenesis, anti-inflammation, and oxygen sensing. Enzymes that produce H₂S, such as cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase have been studied intensively and well characterized. Polysulfides, which have a higher number of inner sulfur atoms than that in H₂S, were recently identified as potential signaling molecules that can activate ion channels, transcription factors, and tumor suppressors with greater potency than that of H₂S. This article focuses on our contribution to the discovery of these molecules and their metabolic pathways and mechanisms of action.