Hydrogen sulfide and polysulfides as signaling molecules

Hydrogen sulfide (H(2)S) is a familiar toxic gas that smells of rotten eggs. After the identification of endogenous H(2)S 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 H(2)S, 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 H(2)S, were recently identified as potential signaling molecules that can activate ion channels, transcription factors, and tumor suppressors with greater potency than that of H(2)S. This article focuses on our contribution to the discovery of these molecules and their metabolic pathways and mechanisms of action.