Physiological roles of hydrogen sulfide and polysulfides

Abstract

Hydrogen sulfide (H 2 S) has been recognized as a signaling molecule as well as a cytoprotective molecule. H 2 S modulates neurotransmission, regulates vascular tone, protects various tissues and organs, regulates inflammation, induces angiogenesis, and detects cellular oxygen levels. H 2 S is produced from L-cysteine bycystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and3-mercaptopyruvate sulfurtransferase (3MST) together with cysteine aminotransferase (CAT). Recently, a novel pathway for the production of H 2 S from D-cysteine was identified, involving D-amino acid oxidase (DAO) together with 3MST. Sulfuration (also called sulfhydration), which adds sulfur atoms to the cysteine residues of target proteins to modify protein activity, has been extensively studied as a mode of H 2 S action. Recently, hydrogen polysulfides (H2S n, where n = 3–7; n = 2 is termed as persulfide) have been found to sulfurate target proteins in the brain, including transient receptor potential ankyrin 1 (TRPA1) channels, Kelch-like ECH-associating protein 1 (Keap1), and phosphatase and tensin homolog (PTEN), much more potently than H 2 S. The physiological stimuli that trigger the production of H2S and polysulfides, and the mechanisms maintaining their local levels, remain unknown. Understanding the regulation of H 2 S n (including H 2 S) production, and the specific stimuli that induce their release, will provide new insight into the biology of H 2 S and will provide novel avenues for therapeutic development in diseases involving H 2 S-related substances.