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Cited by 51Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressElectron Spin Resonance Studies

Involvement of protein radical, protein aggregation, and effects on NO metabolism in the hypochlorite-mediated oxidation of mitochondrial cytochrome c

Chen, Yeong-Renn, Chen, Chwen-Lih, Liu, Xiaoping, Li, Haitao, Zweier, Jay L., Mason, Ronald P.·2004·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2004.07.013
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Abstract

Cytochrome c (cyt c)-derived protein radicals, radical adduct aggregates, and protein tyrosine nitration have been implicated in the pro-apoptotic event connecting inflammation to the development of diseases. During inflammation, one of the reactive oxygen species metabolized via neutrophil activation is hypochlorite (HOCl); destruction of the mitochondrial electron transport chain by hypochlorite is considered to be a damaging factor. Previous study has shown that HOCl induces the site-specific oxidation of cyt c at met-80. In this work, we have assessed the hypothesis that exposure of cyt c to physiologically relevant concentrations of HOCl leads to protein-derived radical and consequent protein aggregation, which subsequently affects cyt c's regulation of nitric oxide metabolism. Reaction intermediates, chemical pathways available for protein aggregation, and protein nitration were examined. A weak ESR signal for immobilized nitroxide derived from the protein was detected when a high concentration of cyt c was reacted with hypochlorite in the presence of the nitroso spin trap 2-methyl-2-nitrosopropane. When a low concentration of cyt c was exposed to the physiologically relevant levels of HOCl in the presence of 5,5-dimethyl-pyrroline N-oxide (DMPO), we detected DMPO nitrone adducts derived from both protein and protein aggregate radicals as assessed by Western blot using an antibody raised against the DMPO nitrone adduct. The cyt c-derived protein radicals formed by HOCl were located on lysine and tyrosine residues, with lysine predominating. Cyt c-derived protein aggregates induced by HOCl involved primarily lysine residues and hydrophobic interaction. In addition, HOCl-oxidized cyt c (HOCl-cyt c) exhibited a higher affinity for NO and enhancement of nonenzymatic NO synthesis from nitrite reduction. Furthermore, HOCl-mediated cyt c oxidation also resulted in a significant elevation of cyt c nitration derived from either NO trapping of the cyt c-derived tyrosyl radical or cyt c-catalyzed one-electron oxidation of nitrite.

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Crossref · 10.1016/j.freeradbiomed.2004.07.013

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  • Zweier, Mason and colleagues demonstrated cytochrome-c mediated nitrite reduction secondary to protein oxidation by hypochlorite.

    “Zweier, Mason and colleagues demonstrated cytochrome-c mediated nitrite reduction secondary to protein oxidation by hypochlorite [72].”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [72]

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Authors
Chen, Y.-R., Chen, C.-L., Liu, X., Li, H., Zweier, J. L., & Mason, R. P.
Affiliations
  • The Ohio State University (US)
  • National Institutes of Health (US)
Corresponding author
Chen, Yeong-Renn
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2004-11
Volume
37
Issue
10
Pages
1591-1603
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2004.07.013
OpenAlex
W2008206866
Cited by
51
References
52
Citations by year
2025: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 4
FWCI
1.32
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01S-HL38324, R01HL063744, HL 65608, P01HL065608, HL 63744)
  • National Institute of Environmental Health Sciences (K22-ES11031, K22ES011031)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
Keywords
cytochrome c, hypochlorite, protein radicals, protein aggregation, nitric oxide metabolism, tyrosine nitration, mitochondrial electron transport chain, nitrite reduction, lysine oxidation, hydrophobic interactions, apoptosis, inflammation, neutrophils
MeSH terms
Animals, Cyclic N-Oxides, Electron Spin Resonance Spectroscopy, Humans, Hypochlorous Acid, Nitric Oxide, Nitrites, Oxidation-Reduction, Protein Binding, Tyrosine, Reactive Oxygen Species, Cytochromes c

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