RXR agonists inhibit oxidative stress-induced apoptosis in H9c2 rat ventricular cells
RXR agonists inhibit oxidative stress-induced apoptosis in H9c2 rat ventricular cells
复制标题
RXR 激动剂抑制 H9c2 大鼠心室细胞氧化应激诱导的细胞凋亡
DOI：
10.1016/j.bbrc.2008.08.074
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发表时间：
2008-10-31
影响因子：
3.1
通讯作者：
He, Ben
中科院分区：
文献类型：
--
作者：
Shan, Peiren;Pu, Jun;He, Ben
视黄酸X受体（Retinoid X receptor，RXR）在调节细胞内受体信号通路中起着重要作用。我们研究了它在调节氧化应激诱导的H9 c2大鼠心室细胞凋亡中的作用。我们首次发现，功能RXR蛋白下调过氧化氢（H2 O2）在H9 c2心肌细胞。RXR的天然和合成激动剂9-cis-RA和LGD 1069分别阻止H2 O2引发的细胞凋亡，并且这种抗凋亡作用被RXR拮抗剂HX 531抑制。进一步研究RXR的保护机制表明，H2 O2诱导的线粒体膜电位的损失，线粒体释放细胞色素c和caspase-3激活都显着减弱预处理RXR激动剂。此外，这种保护与细胞内活性氧的减少和过氧化氢酶活性的上调有关。因此。这些数据表明，RXR的药理学激活通过抗氧化和抗氧化保护机制对H9 c2大鼠心室细胞中H2 O2诱导的细胞凋亡发挥保护作用。(c)2008年爱思唯尔公司All rights reserved.
Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. We examined its role in regulating oxidative stress-induced apoptosis in H9c2 rat ventricular cells. We showed for the first time that functional RXR protein was downregulated by hydrogen peroxide (H2O2) in H9c2 cardiomyocytes. Natural and synthetic agonists of RXR, 9-cis-RA, and LGD1069 respectively, prevented H2O2-triggered apoptosis, and this anti-apoptotic effect was inhibited by the RXR antagonist HX531. Further investigation into the protective mechanisms of RXR demonstrated that H2O2-induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and caspase-3 activation were all significantly attenuated by pretreatment with RXR agonists. Furthermore, this protection was associated with a reduction in intracellular reactive oxygen species and an upregulation in catalase activity. Thus. these data indicate that pharmacological activation of RXR exerts protective effects against H2O2-induced apoptosis in H9c2 rat ventricular cells through antioxidant and mitochondria-protective mechanisms. (c) 2008 Elsevier Inc. All rights reserved.