Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species.
Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species.
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DOI：
10.2217/fca.12.58
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发表时间：
2012-11
影响因子：
1.7
通讯作者：
Webster KA
中科院分区：
文献类型：
--
作者：
Webster KA
活性氧（ROS）的过量产生和细胞内钙离子的积聚在急性心肌梗死时程序性细胞死亡的启动中起主要作用。细胞死亡可包括坏死、凋亡和自噬及其组合。在局部缺血期间，肌浆网和肌丝之间的钙处理被破坏，钙被转移到线粒体，引起肿胀。再灌注虽然对生存至关重要，但重新激活能量转导和收缩性，并导致ROS的释放和额外的离子失衡。在急性缺血再灌注期间，主要的死亡途径是通过内源性途径的程序性坏死和凋亡，分别由线粒体渗透性转换孔的开放和线粒体外膜透化启动。尽管深入研究，线粒体膜透化的作用机制和调节模式还不完全清楚。外源性凋亡、坏死性凋亡和自噬也可能参与缺血再灌注损伤。在这篇综述中，钙和ROS的失调和Bcl-2蛋白的贡献，以及线粒体形态学在促进线粒体膜通透性变化和随后的细胞死亡在心肌梗死的作用进行了讨论。
Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed.