Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function
Abstract
Nitrite, once thought to be an inert biomarker of NO formation, is now recognized as an endocrine storage pool of bioactive NO. While nitrite mediates a number of hypoxic responses, one of its most robust effects is its ability to confer cytoprotection after ischemia/reperfusion in a number of organs and models. The mechanism of this cytoprotection appears to be mediated at the level of the mitochondrion. Here we review the studies demonstrating that nitrite is cytoprotective in the heart and describe the mechanism of this cytoprotection, which involves the post-translational modification of complex I leading to the modulation of mitochondrial reactive oxygen species generation at reperfusion. The mechanism of nitrite-dependent cytoprotection will be compared to other cytoprotective agents including NO and ischemic preconditioning.
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Studies in rodents have shown improvement in atherosclerosis and hypertension after treatment with febuxostat.
“Studies in rodents have shown improvement in atherosclerosis and hypertension after treatment with febuxostat (697, 859).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [859]
Nitrite protects from ischemia-reperfusion injury in vivo and is thought to act as an S-nitrosating agent in ischemic myocardium.
“The nitrite (NO2−) anion protects from ischemia-reperfusion injury in vivo1–3,37 and is thought to act as an S-nitrosating agent in the ischemic myocardium2.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [37]
Shiva et al. demonstrated that the cytoprotective effects of nitrite on ischemia/reperfusion injury are mediated by post-translational S-nitrosylation of complex 1 in the mitochondrial respiratory chain, which inhibits overall mitochondrial ROS formation and apoptotic events.
“Shiva et al., demonstrated that the cytoprotective effects of nitrite on ischemia/reperfusion injury are mediated by post-translational S-nitrosylation of complex 1 in the mitochondrial respiratory chain, which consequently inhibits the overall mitochondrial ROS formation and apoptotic events [101].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [101]
The effect of nitrite on ischemic-reperfusion injury is likely mediated by effects on mitochondrial respiration.
“that is likely mediated by effects on mitochondrial respiration [10].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [10]
Physiologically relevant levels of nitrite counter ischemic-reperfusion injury.
“Physiologically relevant levels of nitrite have been shown to counter ischemic-reperfusion injury [8–10]”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [10]
Nitrite serves as an in vivo reservoir for NO generation, alters mitochondrial function, and manifests a broad array of anti-inflammatory actions in model systems.
“Nitrite serves as an in vivo reservoir for ⅐ NO generation, alters mitochondrial function (54), and manifests a broad array of anti-inflammatory actions in model systems (22).”
From Conjugated linoleic acid is a preferential substrate for fatty acid nitration (2012) · cites this paper as [54]
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References 58 · Cited by 91
- Authors
- Shiva, S., & Gladwin, M. T.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Shiva, Sruti
- Venue
- Basic Research in Cardiology
- Published
- 2009-02-26
- Volume
- 104
- Issue
- 2
- Pages
- 113-119
- ISSN
- 0003-9217 (ISSN-L)
- 0300-8428
- 1435-1803
- OpenAlex
- W2008369604
- Cited by
- 91
- References
- 58
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 10 · 2012: 11
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Basic Research in Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- nitrite, cytoprotection, ischemia-reperfusion injury, mitochondrial function, reactive oxygen species, nitric oxide, hypoxia response, myocardial ischemia, ischemic preconditioning
- MeSH terms
- Animals, Humans, Mitochondria, Heart, Nitrites, Myocardial Reperfusion Injury, Reactive Oxygen Species, Cytoprotection, Electron Transport Complex I
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