Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning.
Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning.
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DOI：
10.1016/j.redox.2014.05.006
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Korthuis RJ
中科院分区：
文献类型：
--
作者：
Kalogeris T;Bao Y;Korthuis RJ
如果缺血时间延长，血供减少会产生相当大的损伤。矛盾的是，缺血器官的灌注恢复会加剧组织损伤并扩大梗塞的范围。作为高代谢器官，心脏和大脑特别容易受到缺血/再灌注（I/R）的有害影响。虽然导致I/ r诱导的组织损伤和梗死的发病机制是多因素的，但每个因素的相对重要性尚不清楚。然而，越来越多的证据表明，线粒体产生活性氧（ROS）在破坏细胞成分和启动细胞死亡中起着关键作用。在这篇综述中，我们总结了我们目前对线粒体ROS生成在I/R中发生并导致心肌梗死和中风的机制的理解。此外，线粒体ROS已被证明参与了几种靶向钾通道（例如，atp敏感钾（mKATP）通道或大电导钙活化钾（mBKCa）通道）的药物预处理，以激活细胞存活程序，使组织和器官更能抵抗I/R的有害影响。最后，我们回顾了选择性靶向mROS产生以减少缺血后组织损伤的新治疗方法，这可能证明在限制心肌功能障碍和梗死以及消除中风中的神经认知缺陷和神经元细胞死亡方面是有效的。
Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke.
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DOI：
10.1124/jpet.104.074476
发表时间：
2005-02-01
影响因子：
3.5
作者：
Cao, CM;Xia, Q;Wong, TM
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作者：
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DOI：
10.1152/ajpheart.1998.275.4.h1283
发表时间：
1998-10-01
影响因子：
4.8
作者：
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影响因子：
4.8
作者：
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影响因子：
10.8
作者：
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