Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function.
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.
Shiva
Sruti
S
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh 15260, USA. Sss43@pitt.edu
Gladwin
Mark T
MT
D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009573:Nitrites / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D009573:Nitrites; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I