title: Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.
abstract: Using methodology developed herein, it is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. These reactive sulfur species were biosynthesized by two major sulfurtransferases: cystathionine β-synthase and cystathionine γ-lyase. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H2O2 and a recently described biologically generated electrophile 8-nitroguanosine 3',5'-cyclic monophosphate. These results indicate that persulfides are potentially important signaling/effector species, and because H2S can be generated from persulfide degradation, much of the reported biological activity associated with H2S may actually be that of persulfides. That is, H2S may act primarily as a marker for the biologically active of persulfide species.
authors.affiliation: Departments of Environmental Health Sciences and Molecular Toxicology and.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ida
authors.affiliation: Departments of Environmental Health Sciences and Molecular Toxicology andPrecursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan;
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.affiliation: Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka 599-8531, Japan;
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ihara
authors.affiliation: Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, Japan;
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, Japan;
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan;
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan;
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Departments of Environmental Health Sciences and Molecular Toxicology and.
authors.forename: Shigemoto
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Departments of Environmental Health Sciences and Molecular Toxicology and.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan;
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; and.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164.
authors.forename: Nelmi O
authors.initials: NO
authors.lastname: Devarie-Baez
authors.affiliation: Department of Chemistry, Washington State University, Pullman, WA 99164.
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jp.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
authors.affiliation: Departments of Environmental Health Sciences and Molecular Toxicology and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: C525106:8-nitroguanosine 3',5'-cyclic monophosphate; D004220:Disulfides; D013438:Sulfhydryl Compounds; C116840:cysteine persulfide; D006861:Hydrogen Peroxide; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006152:Cyclic GMP; D003545:Cysteine
keywords: electrophilic signaling; hydrogen sulfide; polysulfidomics; thiol redox
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