Hydrogen sulfide: its production and functions

Endogenous levels of sulfide in the brain have been measured in rats, humans and bovines in 1989 and 1990, suggesting that H 2 S may have a physiological function. We demonstrated in 1996 that cystathionine β‐synthase can produce H 2 S in the brain and that H 2 S facilitates the induction of hippocampal long‐term potentiation by enhancing the activity of NMDA receptors. The following year, we showed that another H 2 S‐producing enzyme, cystathionine γ‐lyase, is expressed in the thoracic aorta, portal vein and ileum and that H 2 S relaxes these tissues. We proposed that H 2 S may be a neuromodulator as well as a smooth muscle relaxant. In addition to a function as a signalling molecule, we demonstrated another function as a cytoprotectant in 2004. Hydrogen sulfide protects neurons from oxidative stress by reinstating the reduced glutathione levels. We recently demonstrated that a third H 2 S‐producing enzyme, 3‐mercaptopyruvate sulfurtransferase (3MST), is expressed in neurons and vascular endothelium. In addition to reinstating glutathione levels, H 2 S produced by 3MST, which is mainly localized to mitochondria, reduces reactive oxygen species generated in these organelles.