Cited by 312Redox biology and oxidative stressGlutathione Transferases and PolymorphismsSulfur Compounds in Biology

Causes and consequences of cysteine S-glutathionylation

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Grek, Christina L., Zhang, Jie, Manevich, Yefim, Townsend, Danyelle M., Tew, Kenneth D.·2013·Journal of Biological Chemistry

Abstract

Post-translational S-glutathionylation occurs through the reversible addition of a proximal donor of glutathione to thiolate anions of cysteines in target proteins, where the modification alters molecular mass, charge, and structure/function and/or prevents degradation from sulfhydryl overoxidation or proteolysis. Catalysis of both the forward (glutathione S-transferase P) and reverse (glutaredoxin) reactions creates a functional cycle that can also regulate certain protein functional clusters, including those involved in redox-dependent cell signaling events. For translational application, S-glutathionylated serum proteins may be useful as biomarkers in individuals (who may also have polymorphic expression of glutathione S-transferase P) exposed to agents that cause oxidative or nitrosative stress.

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  • Reversible oxidation of Cys residues of complex I, ALDH2, and Prx3 seems protective, despite temporary inactivation, against further tissue damage from irreversible hyper-oxidation of Cys followed by proteolytic degradation.

    “For instance, reversible oxidation of Cys residues of mitochondrial NADH-dependent ubiquinone oxidoreductase (complex I), ALDH2, and Prx3 seem to be protective, despite temporary inactivation, against further tissue damage from irreversible hyper-oxidation of Cys to Cys-sulfinic acid (Cys-SO2) and Cys-sulfonic acid (Cys-SO3) followed by proteolytic degradation [67], [68], as in the case of I/R”

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  1. Singh, S. P., Wishnok, J. S., Keshive, M., Deen, W. M., and Tannenbaum, S. R. (1996) The chemistry of the S-nitrosoglutathione/glutathione sys- tem. Proc. Natl. Acad. Sci. U.S.A. 93, 14428 -14433

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Authors
Grek, C. L., Zhang, J., Manevich, Y., Townsend, D. M., & Tew, K. D.
Affiliations
Medical University of South Carolina (US)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2013-09
Volume
288
Issue
37
Pages
26497-26504
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1964891414
Cited by
312
References
104
Citations by year
2026: 10 · 2025: 11 · 2024: 15 · 2023: 19 · 2022: 16 · 2021: 14 · 2020: 35 · 2019: 28 · 2018: 35 · 2017: 30 · 2016: 38 · 2015: 26 · 2014: 29 · 2013: 6
FWCI
3.11
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1c06rr015455-01a1)
  • National Cancer Institute (R01CA085660, R41CA117259, CA08660, CA117259)
  • National Center for Research Resources (C06 RR-015455, P20RR024485)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords
post-translational modification, glutathione S-transferase pi, glutaredoxin, thiolate anion, protein redox regulation, oxidative stress, nitrosative stress, serum protein biomarkers, proteolysis
MeSH terms
Animals, Cysteine, Glutathione, Glutathione Transferase, Humans, Nitric Oxide, Nitrogen, Oxidation-Reduction, Peroxidases, Protein Processing, Post-Translational, Sulfhydryl Compounds, Serpins, Gene Expression Regulation, Enzymologic, Reactive Oxygen Species, Oxidative Stress, Glutaredoxins

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