title: Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain.
abstract: Hydrogen polysulfides (H2Sn) have a higher number of sulfane sulfur atoms than hydrogen sulfide (H2S), which has various physiological roles. We recently found H2Sn in the brain. H2Sn induced some responses previously attributed to H2S but with much greater potency than H2S. However, the number of sulfur atoms in H2Sn and its producing enzyme were unknown. Here, we detected H2S3 and H2S, which were produced from 3-mercaptopyruvate (3 MP) by 3-mercaptopyruvate sulfurtransferase (3MST), in the brain. High performance liquid chromatography with fluorescence detection (LC-FL) and tandem mass spectrometry (LC-MS/MS) analyses showed that H2S3 and H2S were produced from 3 MP in the brain cells of wild-type mice but not 3MST knockout (3MST-KO) mice. Purified recombinant 3MST and lysates of COS cells expressing 3MST produced H2S3 from 3 MP, while those expressing defective 3MST mutants did not. H2S3 was localized in the cytosol of cells. H2S3 was also produced from H2S by 3MST and rhodanese. H2S2 was identified as a minor H2Sn, and 3 MP did not affect the H2S5 level. The present study provides new insights into the physiology of H2S3 and H2S, as well as novel therapeutic targets for diseases in which these molecules are involved.
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: Yuka
authors.initials: Y
authors.lastname: Kimura
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: Yukiko
authors.initials: Y
authors.lastname: Toyofuku
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.|Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Koike
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: Norihiro
authors.initials: N
authors.lastname: Shibuya
authors.affiliation: Radioisotope Center, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo 113-8602, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.affiliation: Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, LSU Health Science Center, New Orleans, LA 70112, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lefer
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
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: Hideo
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006862:Hydrogen Sulfide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism*; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism*; D013884:Thiosulfate Sulfurtransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D013440:Sulfides; C008366:3-mercaptopyruvic acid; D013466:Sulfurtransferases; D013884:Thiosulfate Sulfurtransferase; C021550:3-mercaptopyruvate sulphurtransferase; D003545:Cysteine; D006862:Hydrogen Sulfide