Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver
Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver
复制标题
DOI：
10.1152/ajpgi.2001.281.4.g1115
复制
发表时间：
2001-10-01
影响因子：
4.5
通讯作者：
Kawasaki, S
中科院分区：
文献类型：
--
作者：
Soeda, J;Miyagawa, S;Kawasaki, S
细胞凋亡在肝脏缺血再灌注损伤中起重要作用。然而，I/R损伤中细胞凋亡的分子基础知之甚少。本研究的目的是确定何时以及如何凋亡信号转导发生在I/R损伤。将90 min热缺血再灌注大鼠的细胞凋亡途径与单独长时间缺血大鼠的细胞凋亡途径进行比较。在缺血过程中，线粒体细胞色素c被释放到细胞质中的肝细胞和窦内皮细胞的时间依赖性的方式，和半胱天冬酶-3和半胱天冬酶激活的DNA酶的抑制剂被裂解。但未观察到细胞凋亡和DNA断裂。再灌注后，细胞核浓缩，末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记阳性，DNA断裂，caspase-8和Bid裂解发生。相反，长时间缺血单独诱导坏死，而不是凋亡。总之，我们的研究结果表明，释放线粒体细胞色素c和半胱天冬酶激活进行缺血，虽然细胞凋亡表现在再灌注后。
Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.