Hydrogen Sulfide (HS) and Polysulfide (HS) Signaling: The First 25 Years.

Since the first description of hydrogen sulfide (HS) as a toxic gas in 1713 by Bernardino Ramazzini, most studies on HS have concentrated on its toxicity. In 1989, Warenycia et al. demonstrated the existence of endogenous HS in the brain, suggesting that HS may have physiological roles. In 1996, we demonstrated that hydrogen sulfide (HS) is a potential signaling molecule, which can be produced by cystathionine β-synthase (CBS) to modify neurotransmission in the brain. Subsequently, we showed that HS relaxes vascular smooth muscle in synergy with nitric oxide (NO) and that cystathionine γ-lyase (CSE) is another producing enzyme. This study also opened up a new research area of a crosstalk between HS and NO. The cytoprotective effect, anti-inflammatory activity, energy formation, and oxygen sensing by HS have been subsequently demonstrated. Two additional pathways for the production of HS with 3-mercaptopyruvate sulfurtransferase (3MST) from l- and d-cysteine have been identified. We also discovered that hydrogen polysulfides (HS, n ≥ 2) are potential signaling molecules produced by 3MST. HS regulate the activity of ion channels and enzymes, as well as even the growth of tumors. -Sulfuration (-sulfhydration) proposed by Snyder is the main mechanism for HS/HS underlying regulation of the activity of target proteins. This mini review focuses on the key findings on HS/HS signaling during the first 25 years.