Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Significance: Accumulating evidence shows that hydrogen sulfide may function as a signaling molecule in processes such as neuromodulation in the brain and smooth muscle relaxation in the vascular system. It also has a cytoprotective effect, since it can protect neurons and cardiac muscle from oxidative stress and ischemia-reperfusion injury, respectively. Hydrogen sulfide can also modulate inflammation, insulin release, and angiogenesis. Recent Advances: The regulation of the activity of 3-mercaptopyruvate sulfur transferase (3MST) along with cysteine aminotransferase (CAT), one of the H2S producing pathways, has been demonstrated. The production of H2S by the pathway, which is regulated by Ca2+ and facilitated by thioredoxin and dihydrolipoic acid, is also involved in H2S signaling as well as cytoprotection. Sulfur hydration of proteins by H2S has been proposed to modulate protein functions. H2S-sensitive fluorescent probes, which enable us to measure the localization of H2S in real time, have been developed. Critical Issues: The basal concentrations of H2S have recently been measured and found to be much lower than those initially reported. However, the concentration of H2S reached in stimulated cells, as well as the regulation of H2S producing enzymes is not well understood. It has been proposed that some of the effects of H2S on the regulation of enzymes and receptors might be explained through the properties of sulfane sulfur (S-0), another form of active sulfur. Future Directions: The determination of H2S concentrations in activated cells using new methods including H2S-sensitive fluorescent probes, as well as the investigation of the effects of H2S using specific inhibitors, may provide better understanding of the physiological function of this molecule. Clarifying mechanisms of H2S activity may also facilitate the development of new therapeutic compounds. Antioxid. Redox Signal. 17, 45-57.