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.