Redox regulation of angiotensin II preconditioning of the myocardium requires MAP kinase signaling (Retracted article. See vol. 53, pg. 742, 2012)
Redox regulation of angiotensin II preconditioning of the myocardium requires MAP kinase signaling (Retracted article. See vol. 53, pg. 742, 2012)
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DOI：
10.1016/j.yjmcc.2006.03.009
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发表时间：
2006-08-01
影响因子：
5
通讯作者：
Das, Dipak K.
中科院分区：
文献类型：
--
作者：
Das, Samarjit;Otani, Hajime;Das, Dipak K.
最近的一项研究证明，活性氧（ROS），通过NADPH氧化酶由血管紧张素II（Ang II）与NADPH氧化酶亚基，p22 phox和gp 91 phox的激活产生，负责血管紧张素II的预处理效果。本研究旨在确定是否类似于缺血预处理（PC），丝裂原活化蛋白（MAP）激酶也参与了心脏的血管紧张素II PC。在不存在或存在Erk（1/2）抑制剂、PD 098059（一种p38 MAPK抑制剂）、SB 202190（一种JNK抑制剂）、SP 600125或活性氧清除剂N-乙酰半胱氨酸（NAC）的情况下，用含有Ang II的KHB（Krebs-Henseleit碳酸氢盐）缓冲液灌注分离的工作大鼠心脏15分钟。所有心脏随后进行30分钟的全脑缺血，随后仅用KHB缓冲液再灌注2小时。通过测定梗死面积、心肌细胞凋亡和心室恢复来检测心肌保护作用。通过测定Akt和Bcl-2介导的存活信号来研究氧化还原和MAP激酶调节。与以前的结果一致，血管紧张素II预处理心脏，证明了改善缺血后心室恢复和减少梗死面积和减少心肌细胞凋亡。Ang II使Akt、Bcl-2和Bad磷酸化，这被NAC、PD 098059或SP 600125阻断，但不被SB 202190阻断。NAC、PD 098059和SP 600125也可阻断Ang II预处理的心肌保护作用，而SB 202190则无此作用。结果表明，Ang II预处理是通过氧化还原信号调节的MAP激酶增强的。(c)2006年爱思唯尔公司All rights reserved.
A recent study documented reactive oxygen species (ROS), generated through NADPH oxidase by angiotensin II (Ang II) with the activation of NADPH oxidase subunits, p22phox and gp91phox, to be responsible for the preconditioning effect of Ang II. The present study was designed to determine if similar to ischemic preconditioning (PC), mitogen-activated protein (MAP) kinases are also involved in Ang II PC of the heart. Isolated working rat hearts were perfused for 15 min with KHB (Krebs-Henseleit bicarbonate) buffer containing Ang II in the absence or presence of an Erk (1/2) inhibitor, PD 098059, a p38MAPK inhibitor, SB 202190, a JNK inhibitor, SP 600125 or a ROS scavenger, N-acetyl cysteine (NAC). All hearts were subsequently subjected to 30 min global ischemia followed by 2 h reperfiision with KHB buffer only. Cardioprotection was examined by determining infarct size, cardiomyocyte apoptosis and ventricular recovery. Redox and MAP kinase regulation were studied by determining the survival signaling mediated by Akt and Bcl-2. In consistent with previous results, Ang II preconditioned the heart as evidenced by improved postischemic ventricular recovery and reduced infaret size and decreases cardiomyocyte apoptosis. Ang II phosphorylated both Akt, Bcl-2 and Bad, which was blocked by NAC, PD 098059 or SP 600125, but not by SB 202190. NAC, PD 098059 and SP600125, but not SB202190, also abolished the cardioprotective effect of Ang II preconditioning. The results indicate that Ang II preconditioning is potentiated through MAP kinases that are regulated by redox signaling. (c) 2006 Elsevier Inc. All rights reserved.