The interplay of nitric oxide and peroxynitrite with signal transduction pathways: Implications for disease
Abstract
Since the discovery that at least one form of endothelium derived relaxing factor is nitric oxide (NO), numerous studies have uncovered diverse roles for this free radical in a variety of physiological and pathophysiological processes. NO production, a process mediated by a family of enzymes termed NO synthases, has been detected in most cell types. Many of the effects of NO are thought to be mediated through its direct interaction with specific and defined cell signaling pathways. The nature of such interactions are highly dependent on the concentration of NO and cell type. Furthermore, specific NO derived reaction products, such as peroxynitrite, also have the potential to effect cell signal transduction events. As with NO, this can occur through diverse mechanisms and depends on concentration and cell type. It is perhaps not surprising that the reported effects of NO in different disease states are often conflicting. In this brief overview, a framework for placing these apparently disparate properties of NO will be described and will focus on the effects of NO and peroxynitrite on signaling pathways.
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Once NO has reacted with O2 ̇̄, it forms peroxynitrite and no longer participates in signaling actions that require binding to ferrous heme.
“Once it has reacted with O2˙̄, it forms peroxynitrite and no longer participates in those signaling actions, which require binding to ferrous heme (23).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [23]
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 [86]
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Self-citation
- Authors
- McAndrew, J., Patel, R. P., Jo, H., Cornwell, T., Lincoln, T., Moellering, D., White, C. R., Matalon, S., & Darley-Usmar, V.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Darley-Usmar, Victor
- ORCID
- Venue
- Seminars in Perinatology
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 21
- Issue
- 5
- Pages
- 351-366
- ISSN
- 0146-0005 (ISSN-L)
- OpenAlex
- W2048272805
- Cited by
- 56
- References
- 128
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Perinatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01hl048676-05)
- National Heart, Lung, and Blood Institute (HL48676-04, R01HL051173, HL51173)
- 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
- nitric oxide, peroxynitrite, signal transduction, nitric oxide synthase, endothelium-derived relaxing factor, free radicals, signaling pathways, disease
- MeSH terms
- Animals, Humans, Nitrates, Nitric Oxide, Oxidation-Reduction, Signal Transduction, Oxidants, Nitric Oxide Synthase
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