Connexin 43 confers resistance to hydrogen peroxide-mediated apoptosis
Connexin 43 confers resistance to hydrogen peroxide-mediated apoptosis
复制标题
DOI：
10.1016/j.bbrc.2007.08.066
复制
发表时间：
2007-10-26
影响因子：
3.1
通讯作者：
Yang, Jay
中科院分区：
文献类型：
--
作者：
Giardina, Sarah F.;Mikami, Maya;Yang, Jay
本研究旨在了解过表达的缝隙连接形成蛋白(CX)43对C6胶质瘤细胞的抗凋亡作用。C6细胞在过氧化氢(H_2O_2)或星形孢菌素作用下表现出与细胞凋亡相一致的形态和生化变化，而表达Cx43的C6细胞对H_2O_2表现出相对的抗性，而对星形孢菌素没有表现出相对的抗性。这种对过氧化氢的选择性保护是由于抑制了表达Cx43的细胞中caspase-3的激活。大鼠原代星形胶质细胞的siRNA敲除实验证实了内源性Cx43介导的抗凋亡作用的存在。Cx43与上游的凋亡信号调节激酶I相互作用，介导过氧化氢诱导的细胞凋亡，提供了一种可能的保护机制。这些发现为Cx43对丝裂原活化蛋白激酶通路和细胞凋亡的调控提供了新的证据，表明该蛋白除了作为质膜上的缝隙连接形成蛋白外，还参与细胞内的信号转导。(C)2007 Elsevier Inc.保留所有权利。
The current study aimed to understand the anti-apoptotic effect of overexpressed gap junction forming protein connexin (Cx) 43 in C6 glioma cells. C6 cells exposed to hydrogen peroxide (H2O2) or staurosporine demonstrated morphological and biochemical changes consistent with apoptosis, whereas C6 cells expressing Cx43 demonstrated relative resistance to H2O2, but not to staurosporine. This selective protection against H2O2 was due to inhibition of caspase-3 activation in Cx43 expressing cells. siRNA knockdown experiments in rat primary astrocytes confirmed the presence of endogenous Cx43-mediated anti-apoptotic effect. Cx43 interacts with the upstream apoptosis signal-regulating kinase I known to mediate H2O2-induced apoptosis providing a possible mechanism for protection. These findings provided new evidence for regulation of the mitogen activated protein kinase pathway and apoptosis by Cx43 implicating this protein in intracellular signaling beyond its role as a gap junction forming protein on the plasma membrane. (c) 2007 Elsevier Inc. All rights reserved.