Hypoxia/Reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase
Hypoxia/Reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase
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DOI：
10.1016/j.yjmcc.2007.05.019
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发表时间：
2007-10-01
影响因子：
5
通讯作者：
Ghafourifar, Pedram
中科院分区：
文献类型：
--
作者：
Zenebe, Woineshet J.;Nazarewicz, Rafal R.;Ghafourifar, Pedram
本研究的目的是阐明线粒体在低氧和复氧诱导的心脏氧化应激中的分子机制。本文介绍了一种可以实时研究线粒体在低氧和复氧状态下的新模型，并描述了线粒体内钙稳态和线粒体一氧化氮合酶(MtNOS)在氧化应激中的意义。本研究表明，在低氧和复氧条件下孵育大鼠心脏线粒体，而不是低氧本身，可引起线粒体细胞色素c的释放，线粒体脂质和蛋白质的氧化修饰，以及易被过氧亚硝酸根灭活的线粒体酶的失活。当mtNOS被抑制或线粒体被抗氧化剂过氧亚硝酸盐清除剂补充时，这些变化被阻止。目前的研究表明，线粒体不依赖于其他细胞成分，通过升高线粒体内游离钙并刺激线粒体一氧化氮合酶来响应缺氧/复氧。本研究提出了心肌线粒体钙稳态和线粒体一氧化氮合酶在缺氧/复氧诱导的氧化应激中的重要作用。(C)2007 Elsevier Inc.保留所有权利。
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. (C) 2007 Elsevier Inc. All rights reserved.