Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury
Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury
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DOI：
10.1161/01.res.0000015224.07870.9a
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发表时间：
2002-04-05
影响因子：
20.1
通讯作者：
Latchman, DS
中科院分区：
文献类型：
--
作者：
Scarabelli, TM;Stephanou, A;Latchman, DS
缺血/再灌注损伤后，细胞凋亡与坏死一起导致心肌细胞丢失。凋亡级联反应由线粒体损伤和半胱天冬酶-9活化或死亡受体连接和半胱天冬酶-8活化启动。在本研究中，在离体大鼠心脏暴露于单独缺血或缺血再灌注，切割的caspase-9主要在内皮细胞中观察到。相反，caspase-8裂解仅在心肌细胞中发现，在整个再灌注过程中逐渐增加。缺血前灌注液中加入特定的caspase-9抑制剂可防止内皮细胞凋亡，而缺血前灌注特定的caspase-8抑制剂仅影响心肌细胞凋亡。此外，caspase-8介导的BID加工仅在再灌注期间观察到。然后，tBID的产生维持线粒体损伤并使胱天蛋白酶-9活化永久化。
Apoptosis contributes, with necrosis, to the cardiac cell loss after ischemia/reperfusion injury. The apoptotic cascade is initiated either by mitochondrial damage and activation of caspase-9 or by death receptor ligation and activation of caspase-8. In the present study, performed in the isolated rat heart exposed either to ischemia alone or ischemia followed by reperfusion, cleavage of caspase-9 was observed primarily in endothelial cells. Conversely, caspase-8 cleavage was only found in cardiomyocytes, where it progressively increased throughout reperfusion. Addition of a specific caspase-9 inhibitor to the perfusate before ischemia prevented endothelial apoptosis, whereas preischemic infusion of a specific caspase-8 inhibitor affected only myocyte apoptosis. Additionally, caspase-8-mediated BID processing was observed only during reperfusion. Production of tBID then sustains mitochondrial injury and perpetuates caspase-9 activation.