Nuclear Translocation of Calpain-2 Regulates Propensity Toward Apoptosis in Cardiomyocytes of Tail-Suspended Rats
Nuclear Translocation of Calpain-2 Regulates Propensity Toward Apoptosis in Cardiomyocytes of Tail-Suspended Rats
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calpain-2的核转位调节尾悬大鼠心肌细胞凋亡的倾向
DOI：
10.1002/jcb.22947
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发表时间：
2011-02-01
影响因子：
4
通讯作者：
Yu, Zhi-Bin
中科院分区：
文献类型：
--
作者：
Chang, Hui;Zhang, Lin;Yu, Zhi-Bin
从长期太空飞行返回后，儿茶酚胺释放的代偿性增加并不能逆转立位不耐受，但尚不清楚高剂量的儿茶酚胺是否会引起心脏损伤。采用尾部悬吊大鼠模型模拟失重对心脏的影响。与同步对照组相比，尾吊4周大鼠左心室心肌细胞凋亡率没有增加。相反，异丙肾上腺素（腹腔注射）和4周尾部悬吊恢复1天会增加心肌细胞凋亡率。普萘洛尔和PD 150606抑制恢复组心肌细胞凋亡。PD 150606和calpain-2敲低也阻断了尾吊大鼠中异丙肾上腺素诱导的心肌细胞凋亡。尾吊大鼠心肌钙蛋白酶-2的活性和核转位增加，但钙蛋白酶-1，钙蛋白酶-2，钙蛋白酶抑制剂的表达不变。在异丙肾上腺素刺激下，尾吊大鼠核膜的Ser-16-磷酸化受磷蛋白高于对照组。异丙肾上腺素处理也诱导了尾吊大鼠心肌细胞核内大量Ca（2+）瞬变。这些结果表明，高剂量异丙肾上腺素磷酸化受磷蛋白的核膜和增加核内钙（2+）瞬变。较大的核内Ca（2+）进一步激活核内钙蛋白酶-2，从而诱导心肌细胞凋亡。J.细胞。112：571-580，2011. (C)2010 Wiley-Liss，Inc.
The compensatory increase in catecholamine release does not reverse orthostatic intolerance after returning from a long-term spaceflight, but it is unclear whether high dose of catecholamine induces cardiac damage. The tail-suspended rat model was used to simulate the effects of weightlessness on the heart. Apoptotic rates in the left ventricular myocardium did not increase in 4-week of tail-suspended rats compared with the synchronous control. On the contrary, isoproterenol (intraperitoneal injection) and 1-day recovery from the 4-week tail-suspension increased apoptotic rates in the myocardium. Propranolol and PD150606 inhibited cardiomyocyte apoptosis in the recovery group. PD150606 and calpain-2 knockdown also blocked isoproterenol-induced cardiomyocyte apoptosis in tail-suspended rats. The activity and nuclear translocation of calpain-2 increased, but the expression of calpain-1, calpain-2, and calpastatin was unchanged in the myocardium of tail-suspended rats. The Ser-16-phosphorylated phospholamban of the nuclear envelope was higher in tail-suspended rats than in the control rats under isoproterenol stimulation. Isoproterenol treatment also induced a large intranuclear Ca(2+) transient of cardiomyocytes in tail-suspended rats. These results suggest that high-dose isoproterenol phosphorylates phospholamban of the nuclear envelope and increases intranuclear Ca(2+) transient. Larger intranuclear Ca(2+) further activates nuclear calpain-2 and hence induces cardiomyocyte apoptosis. J. Cell. Biochem. 112: 571-580, 2011. (C) 2010 Wiley-Liss, Inc.