Abstract
Since our initial demonstrations that hydrogen sulfide (H(2)S) may function as a neuromodulator in the brain and a smooth muscle relaxant in the vascular system, accumulating evidence shows that H(2)S may function as a signaling molecule. We and others also found that H(2)S has a cytoprotective effect. Because H(2)S is well-known toxic gas, a cytoprotective role has been overlooked. H(2)S protects neurons from oxidative stress. It also protects cardiac muscle from ischemia-reperfusion injury. The finding led to the application of H(2)S to the bypass surgery patients in Phase II clinical trial. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are well known as H(2)S-producing enzymes. We recently demonstrated that the other H(2)S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) is localized to neurons in the brain and to the vascular endothelium. However, the regulation of H(2)S production by 3MST/CAT pathway had not been well understood. The present study shows that H(2)S production by 3MST/CAT pathway is regulated by Ca(2+) and that H(2)S protects retinal photoreceptor cells from light induced degeneration by suppressing excessive Ca(2+) influx caused by intense light.