Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 2010 Nov;88(11):1084-92. doi: 10.1139/y10-088.
Ischemia-reperfusion (IR)-induced cell apoptosis involves the activation of c-Jun NH2-terminal kinase (JNK). The activation of JNK requires the presence of scaffold proteins called JNK-interacting proteins (JIP), which bind several members of a signaling cascade for proper signaling specificity. In this study, the expression of scaffold proteins JIP1 and JIP3 and their roles in the regulation of JNK activity were investigated in simulated IR in a cell model (H9c2). JIP1 protein expression was significantly decreased, whereas JIP3 protein expression was increased in IR H9c2 cells. Adenovirus-induced overexpression of JIP1 reduced IR-induced JNK activity and apoptosis. Conversely, overexpression of JIP3 increased JNK activity and apoptosis following IR. Depletion of endogenous JIP1 by siRNA treatment increased the IR-induced JNK activity, whereas siRNA-mediated depletion of endogenous JIP3 inhibited JNK activity. These results suggest that JIP1 and JIP3 play important roles in the activation of JNK during simulated IR challenge in H9c2 cells.
缺血再灌注（IR）诱导的细胞凋亡涉及 c-Jun NH2-末端激酶（JNK）的激活。JNK 的激活需要称为 JNK 相互作用蛋白（JIP）的支架蛋白的存在，这些支架蛋白结合信号转导级联中的几个成员，以实现适当的信号特异性。在这项研究中，在 H9c2 细胞模型中模拟 IR 研究了支架蛋白 JIP1 和 JIP3 的表达及其在调节 JNK 活性中的作用。IR H9c2 细胞中 JIP1 蛋白表达显著降低，而 JIP3 蛋白表达增加。腺病毒诱导的 JIP1 过表达可降低 IR 诱导的 JNK 活性和细胞凋亡。相反，IR 后 JIP3 的过表达增加了 JNK 活性和细胞凋亡。用 siRNA 处理耗尽内源性 JIP1 会增加 IR 诱导的 JNK 活性，而 siRNA 介导的内源性 JIP3 耗竭则抑制 JNK 活性。这些结果表明，JIP1 和 JIP3 在 H9c2 细胞模拟 IR 挑战期间 JNK 的激活中发挥重要作用。
