Hypoxia/Reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase

Abstract The objective of the present study was to delineate the molecular mechanisms for mitochondrial contribution to oxidative stress induced by hypoxia and reoxygenation in the heart. The present study introduces a novel model allowing real-time study of mitochondria under hypoxia and reoxygenat...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2007-10, Vol.43 (4), p.411-419
Main Authors: Zenebe, Woineshet J, Nazarewicz, Rafal R, Parihar, Mordhwaj S, Ghafourifar, Pedram
Format: Article
Language:English
Subjects:
Animals
Calcium
Calcium - metabolism
Calcium - physiology
Cardiovascular
Cytochromes c - metabolism
Heart - drug effects
Hypoxia
Hypoxia - metabolism
In Vitro Techniques
Mitochondria
Mitochondria, Heart - enzymology
Models, Biological
mtNOS
Myocardial Reperfusion Injury - pathology
Myocardium - metabolism
Myocardium - pathology
Nitric Oxide Synthase - physiology
Oxidative Stress
Oxygen - pharmacology
Rats
Rats, Sprague-Dawley
Reoxygenation
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Summary:Abstract The objective of the present study was to delineate the molecular mechanisms for mitochondrial contribution to oxidative stress induced by hypoxia and reoxygenation in the heart. The present study introduces a novel model allowing real-time study of mitochondria under hypoxia and reoxygenation, and describes the significance of intramitochondrial calcium homeostasis and mitochondrial nitric oxide synthase (mtNOS) for oxidative stress. The present study shows that incubating isolated rat heart mitochondria under hypoxia followed by reoxygenation, but not hypoxia per se , causes cytochrome c release from the mitochondria, oxidative modification of mitochondrial lipids and proteins, and inactivation of mitochondrial enzymes susceptible to inactivation by peroxynitrite. These alterations were prevented when mtNOS was inhibited or mitochondria were supplemented with antioxidant peroxynitrite scavengers. The present study shows mitochondria independent of other cellular components respond to hypoxia/reoxygenation by elevating intramitochondrial ionized calcium and stimulating mtNOS. The present study proposes a crucial role for heart mitochondrial calcium homeostasis and mtNOS in oxidative stress induced by hypoxia/reoxygenation.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2007.05.019