Journal article
Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling
Proceedings of the National Academy of Sciences - PNAS, Vol.111(21), pp.7606-7611
05/27/2014
Handle:
https://hdl.handle.net/2376/111511
PMCID: PMC4040604
PMID: 24733942
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.
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Details
- Title
- Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling
- Creators
- Tomoaki Ida - Departments of Environmental Health Sciences and Molecular Toxicology andTomohiro Sawa - Departments of Environmental Health Sciences and Molecular Toxicology andPrecursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, JapanHideshi Ihara - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka 599-8531, JapanYukihiro Tsuchiya - Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, JapanYasuo Watanabe - Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, JapanYoshito Kumagai - Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, JapanMakoto Suematsu - Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, JapanHozumi Motohashi - Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, JapanShigemoto Fujii - Departments of Environmental Health Sciences and Molecular Toxicology andTetsuro Matsunaga - Departments of Environmental Health Sciences and Molecular Toxicology andMasayuki Yamamoto - Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanKatsuhiko Ono - Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; andNelmi O Devarie-Baez - Department of Chemistry, Washington State University, Pullman, WA 99164Ming Xian - Department of Chemistry, Washington State University, Pullman, WA 99164Jon M Fukuto - Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jpTakaaki Akaike - Departments of Environmental Health Sciences and Molecular Toxicology and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jp
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(21), pp.7606-7611
- Academic Unit
- Chemistry, Department of
- Publisher
- United States
- Grant note
- R15 HL106598 / NHLBI NIH HHS R01 HL116571 / NHLBI NIH HHS HL106598 / NHLBI NIH HHS R01HL116571 / NHLBI NIH HHS
- Identifiers
- 99900547593301842
- Language
- English
- Resource Type
- Journal article