SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury
SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury
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姜黄素预处理激活 SIRT1 可减轻心肌缺血再灌注损伤引起的线粒体氧化损伤
DOI：
10.1016/j.freeradbiomed.2013.07.007
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发表时间：
2013-12-01
影响因子：
7.4
通讯作者：
Jin, Zhenxiao
中科院分区：
文献类型：
--
作者：
Yang, Yang;Duan, Weixun;Jin, Zhenxiao
缺血再灌注损伤（IRI）是心血管系统的一种损伤，可引起线粒体氧化应激。沉默信息调节因子1（SIRT1）是一种组蛋白去乙酰化酶，参与了IRI。姜黄素（Curcumin，Cur）是一种强的天然抗氧化剂，是姜黄中的活性成分，对IRI具有保护作用，并可能调节SIRT1的活性。本研究旨在探讨Cur预处理对心肌IRI的保护作用及其可能机制。对分离的和体内的大鼠心脏和培养的新生大鼠心肌细胞进行IR。在此过程之前，将心脏或心肌细胞在不存在或存在SIRT1抑制剂sirtinol或SIRT1 siRNA的情况下暴露于Cur。Cur具有心脏保护作用，表现为改善缺血后心脏功能，减少心肌梗死面积，降低心肌凋亡指数，以及几个生化参数，包括上调抗凋亡蛋白Bcl 2和下调促凋亡蛋白Bax。Sirtinol和SIRT1 siRNA均通过抑制SIRT1信号传导阻断Cur介导的心脏保护作用。Cur还导致线粒体氧化还原电位保存完好，线粒体超氧化物歧化酶活性显著升高，线粒体过氧化氢和丙二醛的形成减少。这些观察结果表明，IR诱导的线粒体氧化损伤显着减弱。然而，这种Cur升高的线粒体功能被sirtinol或SIRT1 siRNA处理逆转。总之，我们的结果表明，Cur预处理通过SIRT1信号转导的激活减少IR诱导的线粒体氧化损伤来减弱IRI。(C)2013 Elsevier Inc. All rights reserved.
Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling. (C) 2013 Elsevier Inc. All rights reserved.