Peroxynitrite Detoxification and Its Biologic Implications
Abstract
Peroxynitrite is a cytotoxic oxidant formed in vivo from the diffusional-controlled reaction between nitric oxide and superoxide radicals. Increased peroxynitrite formation has been related to the pathogenesis of multiple diseases, thus underlining the importance of understanding the mechanisms of its detoxification. In nature, different enzymatic routes for peroxynitrite decomposition have evolved. Among them, peroxiredoxins catalytically reduce peroxynitrite in vitro; modulation of their expression affects peroxynitrite-mediated cytotoxicity, and their content changes in pathologic conditions associated with increased peroxynitrite formation in vivo, thus indicating a physiologic role of these enzymes in peroxynitrite reduction. Selenium-containing glutathione peroxidase also catalyzes peroxynitrite reduction, but its role in vivo is still a matter of debate. In selected cellular systems, heme proteins also play a role in peroxynitrite detoxification, such as its isomerization by oxyhemoglobin in red blood cells. Moreover, different pharmacologic approaches have been used to decrease the toxicity related to peroxynitrite formation. Manganese or iron porphyrins catalyze peroxynitrite decomposition, and their protective role in vivo has been confirmed in biologic systems. Glutathione peroxidase mimetics also rapidly reduce peroxynitrite, but their biologic role is less well established. Flavonoids, nitroxides, and tyrosine-containing peptides decreased peroxynitrite-mediated toxicity under different conditions, but their mechanism of action is indirect.
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The fate of NO is dramatically changed in the presence of other free radicals such as superoxide.
“Biologically, this means that the fate of NO is dramatically changed in the presence of other free radicals such as superoxide (O2˙̄) (2, 20–22).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [20]
The presence of free radicals such as superoxide changes the fate of NO: once reacted, it forms peroxynitrite and can no longer bind to ferrous heme.
“The presence of free radicals such as superoxide (O2.−) [82-85] changes the fate of NO: once reacted, it forms peroxynitrite [82, 84, 85] and can no longer bind to ferrous heme [86].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [83]
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Function of Thioredoxin Reductase as a Peroxynitrite Reductase Using Selenocystine or Ebselen
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What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology
Hill, B. G., Dranka, B. P., Bailey, S. M., Lancaster, J. R., & Darley-Usmar, V. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.101618 · Cited by 310 · see citing works
Regulation of obesity and insulin resistance by nitric oxide
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“The presence of free radicals such as superoxide (O2 ) [82–85] changes the fate of NO: once reacted, it forms peroxynitrite [82,84,85] and can no longer bind to ferrous heme [86].”
BackgroundOne- and two-electron oxidation of thiols: mechanisms, kinetics and biological fates
Trujillo, M., Alvarez, B., & Radi, R. (2016) · Free Radical Research · doi:10.3109/10715762.2015.1089988 · Cited by 142 · see citing works
Self-citation
- Authors
- Trujillo, M., Ferrer-Sueta, G., & Radi, R.
- Affiliations
- Universidad de la República de Uruguay (UY)
- Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
- Departamento de Bioquímica, Universidad de la República, Montevideo, Uruguay.
- ORCID
- Trujillo, Madia
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2008-09
- Volume
- 10
- Issue
- 9
- Pages
- 1607-1620
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2131163406
- Cited by
- 97
- References
- 146
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 7 · 2017: 5 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- International Centre for Genetic Engineering and Biotechnology
- Comisión Nacional de Investigación Científica y Tecnológica
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- peroxynitrite, peroxiredoxin, glutathione peroxidase, nitric oxide, superoxide, heme proteins, oxyhemoglobin, porphyrins, glutathione peroxidase mimetics, flavonoids, nitroxide radicals, tyrosine-containing peptides, cytotoxicity, oxidative stress
- MeSH terms
- Animals, Glutathione Peroxidase, Humans, Isomerism, Models, Biological, Nitrites, Oxidation-Reduction, Oxyhemoglobins, Peroxynitrous Acid, Peroxiredoxins
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