细胞生物学
硫氧还蛋白
线粒体
ASK1
细胞色素c
细胞凋亡
生物
程序性细胞死亡
氧化应激
信号转导
p38丝裂原活化蛋白激酶
半胱氨酸蛋白酶
氧化还原
活性氧
凋亡体
蛋白激酶A
内源性凋亡
激酶
细胞内
氧化磷酸化
细胞
化学
生物化学
坏死性下垂
谷胱甘肽
丝裂原活化蛋白激酶激酶
作者
Shugo Ueda,Hiroshi Masutani,Hajime Nakamura,Toru Tanaka,Masaya Ueno,Junji Yodoi
标识
DOI:10.1089/15230860260196209
摘要
Cellular redox is controlled by the thioredoxin (Trx) and glutathione (GSH) systems that scavenge harmful intracellular reactive oxygen species (ROS). Oxidative stress also evokes many intracellular events including apoptosis. There are two major pathways through which apoptosis is induced; one involves death receptors and is exemplified by Fas-mediated caspase-8 activation, and another is the stress- or mitochondria-mediated caspase-9 activation pathway. Both pathways converge on caspase-3 activation, resulting in nuclear degradation and cellular morphological change. Oxidative stress induces cytochrome c release from mitochondria and activation of caspases, p53, and kinases, including apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Trx inhibits apoptosis signaling not only by scavenging intracellular ROS in cooperation with the GSH system, but also by inhibiting the activity of ASK1 and p38. Mitochondria-specific thioredoxin (Trx-2) and Trx peroxidases (peroxiredoxins) are suggested to regulate cytochrome c release from mitochondria, which is a critical early step in the apoptotis-signaling pathway. dATP/ATP and reducing factors including Trx determine the manifestation of cell death, apoptosis or necrosis, by regulating the activation process and the activity of redox-sensitive caspases. As mitochondria are the most redox-active organelle and indispensable for cells to initiate or inhibit the apoptosis process, the regulation of mitochondrial function is the central focus in the research field of apoptosis and redox.
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