Provoking Neuroprotection by Peroxynitrite
Abstract
Peroxynitrite, the product of the reaction between nitric oxide and superoxide, is spontaneouly formed within most mammalian cells under physiological conditions. Initial work addressing the pathophysiology of peroxynitrite afforded the generally accepted notion that this compound would be the long-term neurotoxic nitric oxide-derivative. However, over the past six years a number of interesting studies have reported direct in vivo and in vitro evidence that, at nanomolar-low micromolar concentrations, peroxynitrite is actively involved in triggering cellular survival signals. Most such evidence came from studies demonstrating protection against myocardial ischemia-reperfusion injury and neuronal apoptosis. Although full elucidation of the precise mechanism responsible for such protection still requires further research, peroxynitrite has been shown to promote the nitration and/or phosphorylation of regulatory sites at tyrosine kinase receptors coupled to well-known antiapoptotic pathways, such as those involving phosphoinositide 3-kinase/Akt or mitogen-activated protein kinases. In addition, peroxynitrite-mediated transient protection of neurons against apoptotic death is associated with rapid stimulation of glucose metabolism and glutathione regeneration. In view of the potential cytoprotective function of peroxynitrite, further studies specifically focused on elucidating the possible therapeutic potential of peroxynitrite are sure to appear.
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Although constitutively expressed, the HIF-1α subunit has a very short half-life in normoxic conditions because of its rapid hydroxylation by prolyl-4 hydroxylases (PH1-3).
“Although constitutively expressed, the HIF-1α subunit has a very short half-life in normoxic conditions because of its rapid hydroxylation by prolyl-4 hydroxylases (PH1–3) (12, 36).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [36]
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“These and other studies [reviewed in (39)] indicate that low levels of ONOO ̄, like low levels of H2O2, have a potential cytoprotective effect that could be explored therapeutically.”
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- Authors
- Bolanos, J., Garcia-Nogales, P., & Almeida, A.
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2004-03-01
- Volume
- 10
- Issue
- 8
- Pages
- 867-877
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W1964918959
- Cited by
- 47
- References
- 0
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- 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 › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- peroxynitrite, neuroprotection, nitric oxide, superoxide, myocardial ischemia-reperfusion injury, neuronal apoptosis, receptor tyrosine kinase, phosphatidylinositol 3-kinase/Akt signaling, mitogen-activated protein kinase, glutathione regeneration, glucose metabolism, cytoprotection
- MeSH terms
- Animals, Cell Survival, Glutathione, Humans, Neurons, Sulfhydryl Compounds, Tyrosine, Signal Transduction, Up-Regulation, Cell Death, Cytoprotection, Receptor Protein-Tyrosine Kinases, Peroxynitrous Acid
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