Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways
Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways
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DOI：
10.1016/j.bbrc.2016.03.114
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发表时间：
2016-04-29
影响因子：
3.1
通讯作者：
Wang, Guangji
中科院分区：
文献类型：
--
作者：
Wang, Zhiqiang;Huang, He;Wang, Guangji
缺血性心脏病是现代社会最常见的疾病之一。血管再通治疗可挽救缺血心肌，但其益处因再灌注过程中可能发生的损伤而减弱。凋亡细胞死亡在心肌缺血再灌注损伤中起重要作用。g蛋白信号传导5 （RGS5）是一种鸟苷三磷酸酶激活蛋白，在成人心脏的不同细胞类型中高度表达，可抑制促进心脏ir诱导凋亡的c-Jun nh2末端激酶1/2 （JNK1/2）和p38等多种信号通路。然而，RGS5在ir诱导的心脏细胞凋亡中的作用尚不清楚。建立野生型小鼠（WT）、rgs5转基因小鼠（TG）和rgs5敲除小鼠（KO）离体心脏的体外IR模型。我们的研究结果显示，与WT或KO小鼠相比，TG小鼠表现出心肌细胞凋亡的抑制作用，表现为B细胞淋巴瘤/ lewkia -2 （Bcl-2）的增加，以及末端脱氧核苷酸转移酶介导的dUTP nick end标记（TUNEL）， Bcl-2相关X蛋白（Bax）和活性caspase-3的阳性表达明显减少。此外，JNK1/2和p38信号的抑制显著逆转ir诱导的RGS5-KO小鼠心肌细胞凋亡。这些研究表明RGS5通过抑制JNK1/2和p38信号通路保护心肌细胞免受IR期间的凋亡。(C) 2016 Elsevier Inc.版权所有。
Ischemic heart disease is one of the most common diseases in modern society. Ischemic myocardium can be salvaged by vascular recanalization therapy, but its benefit is attenuated by injury that can occur during reperfusion. And apoptotic cell death plays an important part in myocardial ischemia-reperfusion (IR) injury. Regulator of G-protein signaling 5 (RGS5), highly expressed in different cell types of the human adult heart, is a guanosine triphosphatase-activating protein to inhibit many signaling pathways such as c-Jun NH2-terminal kinase 1/2 (JNK1/2) and p38 which promote cardiac IR-induced apoptosis. However the role of RGS5 in cardiac IR-induced apoptosis remains unclear. An in vitro IR model was applied to the isolated hearts of wild type mice (WT), RGS5-transgenic mice (TG), and RGS5-knockout mice (KO). Our results revealed that compared with either WT or KO mice, TG mice showed inhibition of cardiomyocyte apoptosis as indicated by a greater increase of B cell lymphoma/lewkmia-2 (Bcl-2), and an obvious reduction in the positive expression of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Bcl-2 Associated X protein (Bax), and active caspase-3. Moreover, the inhibition of both JNK1/2 and p38 signaling markedly reversed IR-induced cardiomyocyte apoptosis in RGS5-KO mice. These studies show that RGS5 protects cardiomyocytes against apoptosis during IR through inhibiting both JNK1/2 and p38 signaling pathways. (C) 2016 Elsevier Inc. All rights reserved.