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Proc Natl Acad Sci U S A. 2014 May 27;111(21):7606-11. doi: 10.1073/pnas.1321232111. Epub 2014 Apr 14.

Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.

Author information

1
Departments of Environmental Health Sciences and Molecular Toxicology and.
2
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;
3
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka 599-8531, Japan;
4
Laboratory of Pharmacology, Showa Pharmaceutical University, Tokyo 194-8543, Japan;
5
Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;
6
Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan;
7
Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan;
8
Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan;
9
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; and.
10
Department of Chemistry, Washington State University, Pullman, WA 99164.
11
Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928; and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jp.
12
Departments of Environmental Health Sciences and Molecular Toxicology and jon.fukuto@sonoma.edu takaike@med.tohoku.ac.jp.

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.

KEYWORDS:

electrophilic signaling; hydrogen sulfide; polysulfidomics; thiol redox

Comment in

PMID:
24733942
PMCID:
PMC4040604
DOI:
10.1073/pnas.1321232111
[Indexed for MEDLINE]
Free PMC Article

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