title: Hydrogen sulfide protects the retina from light-induced degeneration by the modulation of Ca2+ influx.
abstract: Hydrogen sulfide (H(2)S) has recently been recognized as a signaling molecule as well as a cytoprotectant. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are well-known as H(2)S-producing enzymes. We recently demonstrated that 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) produces H(2)S in the brain and in vascular endothelium. However, the cellular distribution and regulation of these enzymes are not well understood. Here we show that 3MST and CAT are localized to retinal neurons and that the production of H(2)S is regulated by Ca(2+); H(2)S, in turn, regulates Ca(2+) influx into photoreceptor cells by activating vacuolar type H(+)-ATPase (V-ATPase). We also show that H(2)S protects retinal neurons from light-induced degeneration. The excessive levels of light exposure deteriorated photoreceptor cells and increased the number of TUNEL- and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. Degeneration was greatly suppressed in the retina of mice administered with NaHS, a donor of H(2)S. The present study provides a new insight into the regulation of H(2)S production and the modulation of the retinal transmission by H(2)S. It also shows a cytoprotective effect of H(2)S on retinal neurons and provides a basis for the therapeutic target for retinal degeneration.
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mikami
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shibuya
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kimura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Hideo
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008027:Light / Q000009:adverse effects*; D051379:Mice; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology; D012162:Retinal Degeneration / Q000201:enzymology* / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013466:Sulfurtransferases / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000637:Transaminases; C019968:cysteine aminotransferase; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D025262:Vacuolar Proton-Translocating ATPases; D002118:Calcium; D006862:Hydrogen Sulfide