Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide

Beckman, J S; Beckman, T W; Chen, J; Marshall, P A; Freeman, B A

doi:10.1073/pnas.87.4.1620

Cited by 7,029Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide

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Beckman, J S, Beckman, T W, Chen, J, Marshall, P A, Freeman, B A·1990·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.87.4.1620PMC PMC53527

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Abstract

Superoxide dismutase reduces injury in many disease processes, implicating superoxide anion radical (O2-.) as a toxic species in vivo. A critical target of superoxide may be nitric oxide (NO.) produced by endothelium, macrophages, neutrophils, and brain synaptosomes. Superoxide and NO. are known to rapidly react to form the stable peroxynitrite anion (ONOO-). We have shown that peroxynitrite has a pKa of 7.49 +/- 0.06 at 37 degrees C and rapidly decomposes once protonated with a half-life of 1.9 sec at pH 7.4. Peroxynitrite decomposition generates a strong oxidant with reactivity similar to hydroxyl radical, as assessed by the oxidation of deoxyribose or dimethyl sulfoxide. Product yields indicative of hydroxyl radical were 5.1 +/- 0.1% and 24.3 +/- 1.0%, respectively, of added peroxynitrite. Product formation was not affected by the metal chelator diethyltriaminepentaacetic acid, suggesting that iron was not required to catalyze oxidation. In contrast, desferrioxamine was a potent, competitive inhibitor of peroxynitrite-initiated oxidation because of a direct reaction between desferrioxamine and peroxynitrite rather than by iron chelation. We propose that superoxide dismutase may protect vascular tissue stimulated to produce superoxide and NO. under pathological conditions by preventing the formation of peroxynitrite.

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Authors: Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A.
Affiliations: University of Alabama at Birmingham (US)
Department of Anesthesiology, University of Alabama, Birmingham 35233.
ORCID: Beckman, J S
Marshall, P A
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1990-02
Volume: 87
Issue: 4
Pages: 1620-1624
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.87.4.1620
PMC: PMC53527
OpenAlex: W2058137293
Cited by: 7,029
References: 25
Citations by year: 2026: 33 · 2025: 43 · 2024: 76 · 2023: 75 · 2022: 84 · 2021: 83 · 2020: 96 · 2019: 94 · 2018: 104 · 2017: 123 · 2016: 123 · 2015: 124 · 2014: 179 · 2013: 160 · 2012: 187
FWCI: 67.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health (5r01ns024275-04)
National Institute of Neurological Disorders and Stroke (NS 24338, NS24275)
Topics: Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: peroxynitrite, hydroxyl radicals, superoxide dismutase, nitric oxide, superoxide, endothelial injury, peroxynitrite decomposition, deferoxamine, deoxyribose oxidation, dimethyl sulfoxide oxidation, pKa, oxidative stress
MeSH terms: Animals, Endothelium, Vascular, Free Radicals, Half-Life, Hydrogen-Ion Concentration, Hydroxides, Kinetics, Models, Biological, Nitrates, Nitric Oxide, Peroxides, Superoxides, Superoxide Dismutase, Hydroxyl Radical

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Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide

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