Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia.
Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia.
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DOI：
10.3390/ijms12107199
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发表时间：
2011
影响因子：
5.6
通讯作者：
Chuang YC
中科院分区：
文献类型：
--
作者：
Chen SD;Yang DI;Lin TK;Shaw FZ;Liou CW;Chuang YC
线粒体的主要生理功能是通过电子传递链通过氧化磷酸化产生三磷酸腺苷。线粒体产生的副产物活性氧（ROS）的过度产生与急性脑损伤如脑缺血引起的中风有关。大量研究表明，神经元凋亡途径涉及促凋亡蛋白和抗凋亡蛋白的结合，细胞色素c的释放，最终导致神经元死亡。另一方面，线粒体也起着抵消过度氧化应激引起的有害作用的作用。最近的研究表明，氧化应激和缺血神经元的氧化还原状态也参与了涉及过氧化物酶体增殖激活受体-γ（PPARγ）共激活因子1α（PGC 1-α）的信号通路。PGC 1-α是包括锰超氧化物歧化酶2和解偶联蛋白2在内的ROS清除酶的主要调节剂，两者都是线粒体蛋白，并且可能有助于神经元存活。PGC 1-α还参与对细胞存活至关重要的线粒体生物合成。实验证据支持线粒体功能障碍和氧化应激作为脑卒中后神经元死亡的决定因素以及内源性保护机制的作用。本文综述了近年来有关脑缺血的分子机制，包括ROS、线粒体功能障碍、细胞凋亡、清除ROS的线粒体蛋白和线粒体生物合成等。
The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.
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