The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Abstract
Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
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In the citing paper
“The Aβ (22–35)-induced increases in O2·- and NO· leads to formation of ONOO− attributable to the diffusion-controlled reaction between O2·- and NO· (Beckman and Koppenol, 1996).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Beckman and Koppenol, 1996
In the citing paper
“Therefore, the superoxide generated by the uncoupled eNOS not only induces toxic effects on its own but 1) acts as a NO scavenger, decreasing NO availability and 2) generates peroxynitrite, a more harmful species (78).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“Peroxynitrite is a strong oxidant and nitrosating species (78).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“This observation is not unexpected, as metal-thiol bonds are some of the main targets of peroxynitrite (78, 526).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“This reaction occurs at a diffusion-limited rate and is governed by the flux of NO and superoxide production (78).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“Reaction of peroxynitrite with Zn/S clusters such as that present in eNOS, causes dysfunction of the enzyme as outlined above (sect. IIIB3) (78, 526).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“This modification is measured as the hallmark of peroxynitrite presence and is traditionally viewed as a sign of nitrative or oxidative stress (78, 765).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
In the citing paper
“Despite its rapid rate of formation, peroxynitrite reacts relatively slowly in comparison with other RNS, with many biomolecules, including metal centers, proteins, DNA, and lipids (78, 526, 709).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [78]
Citations
Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
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Self-citationMotor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
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Regulation of biosynthesis of nitric oxide.
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Amyotrophic Lateral Ssclerosis and Structural Defects in Cu,Zn Superoxide Dismutase
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Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.
Stamler, J. S., Jaraki, O., Osborne, J., Simon, D. I., Keaney, J., Vita, J., Singel, D., Valeri, C. R., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7674 · Cited by 1,238
Cited by
Sorted by citations
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
Self-citationMitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
Pathobiology of ischaemic stroke: an integrated view
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01401-0 · Cited by 3,943
Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases
Phaniendra, A., Jestadi, D. B., & Periyasamy, L. (2015) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-014-0446-0 · Cited by 2,886
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238
Metadata
- Authors
- Beckman, J. S., & Koppenol, W. H.
- Affiliations
- University of Alabama at Birmingham (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1996-11-01
- Volume
- 271
- Issue
- 5
- Pages
- C1424-C1437
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W1821918060
- Cited by
- 5,513
- References
- 76
- Citations by year
- 2026: 41 · 2025: 56 · 2024: 69 · 2023: 85 · 2022: 95 · 2021: 110 · 2020: 127 · 2019: 124 · 2018: 142 · 2017: 160 · 2016: 141 · 2015: 172 · 2014: 225 · 2013: 206 · 2012: 212
- FWCI
- 97.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl046407-02, 5p01hl048676-05)
- National Heart, Lung, and Blood Institute (HL-46407, HL48676)
- National Institute of Neurological Disorders and Stroke (NS 24338)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- nitric oxide, superoxide, peroxynitrite, nitric oxide diffusion, oxyhemoglobin, superoxide dismutase, nitrotyrosine, protein nitration, filament assembly, oxidative stress, atherosclerosis, myocardial ischemia, inflammatory bowel disease, amyotrophic lateral sclerosis, neuronal network oscillations, synaptic plasticity
- MeSH terms
- Animals, Arteriosclerosis, Endothelium, Vascular, Humans, Models, Biological, Muscle, Smooth, Vascular, Neurons, Nitrates, Nitric Oxide, Oxyhemoglobins, Superoxides, Superoxide Dismutase, Synapses, Second Messenger Systems
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