Oxidative stress-mediated up-regulation of myocardial ischemic preconditioning up-regulated protein 1 gene expression in H9c2 cardiomyocytes is regulated by cyclic AMP-response element binding protein
Oxidative stress-mediated up-regulation of myocardial ischemic preconditioning up-regulated protein 1 gene expression in H9c2 cardiomyocytes is regulated by cyclic AMP-response element binding protein
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氧化应激介导的心肌缺血预处理上调 H9c2 心肌细胞中蛋白 1 基因表达受环 AMP 反应元件结合蛋白的调节
DOI：
10.1016/j.freeradbiomed.2010.05.004
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发表时间：
2010-08-15
影响因子：
7.4
通讯作者：
Xiao, Xianzhong
中科院分区：
文献类型：
--
作者：
Qu, Shunlin;Zhu, Honglin;Xiao, Xianzhong
环腺苷酸（cAMP）/蛋白激酶A（PKA）级联反应在心肌细胞增殖和凋亡中起着重要作用。在这里，我们表明，过氧化氢刺激表达的抗凋亡心肌缺血预处理上调蛋白1（Mipu 1）基因在H9 c2心肌细胞通过涉及cAMP反应元件结合蛋白（CREB）的途径。H2 O2刺激H9 c2心肌细胞导致Mipu 1启动子活性增加。对大鼠Mipu 1启动子的分析揭示了两个潜在的cAMP反应元件，其中之一（CRE-II，TGTGGATGTTGACGAGCTTGT）使用诱变和缺失分析显示是功能性的。随后的研究证实，H2 O2通过PKA活化途径增加CREB丝氨酸133的磷酸化。磷酸化CREB被证明结合到CRE-II的Mipu 1启动子，和H2 O2处理导致增加他们的相互作用所评估的ChIP。此外，H2 O2介导的Mipu 1蛋白表达的上调被废除的CREB表达与CREB的小干扰RNA的抑制。结果表明，H2 O2诱导的H9 c2心肌细胞Mipu 1表达上调是通过cAMP/PKA依赖的CREB激活介导的。(C)2010年爱思唯尔公司All rights reserved.
The cyclic AMP (cAMP)/protein kinase A (PKA) cascade plays a central role in cardiomyocyte proliferation and apoptosis. Here, we show that H2O2 stimulates expression of the antiapoptotic myocardial ischemic preconditioning up-regulated protein 1 (Mipu1) gene in H9c2 cardiomyocytes through a pathway involving the CAMP-response element binding protein (CREB). Stimulation of H9c2 cardiomyocytes with H2O2 resulted in increased Mipu1 promoter activity. Analysis of the rat Mipu1 promoter revealed two potential cAMP-response elements, one of which (CRE-II, TGTGGATGTTGACGAGCTTGT) was shown, using mutagenesis and deletion analysis, to be functional. Subsequent studies established that H2O2 increased phosphorylation of CREB serine 133 through a pathway involving PKA activation. Phospho-CREB was demonstrated to bind to CRE-II of the Mipu1 promoter, and H2O2 treatment resulted in increases in their interaction as assessed by ChIP. Furthermore, H2O2-mediated up-regulation of Mipu1 protein expression was abrogated by the suppression of CREB expression with small interfering RNA of CREB. It was demonstrated that the H2O2-induced up-regulation of Mipu1 in H9c2 cardiomyocytes was mediated by cAMP/PKA-dependent CREB activation. (C) 2010 Elsevier Inc. All rights reserved.