Alcohol exposure increases the expression of cardiac transcription factors through ERK1/2-mediated histone3 hyperacetylation in H9c2 cells
Alcohol exposure increases the expression of cardiac transcription factors through ERK1/2-mediated histone3 hyperacetylation in H9c2 cells
复制标题
酒精暴露通过 H9c2 细胞中 ERK1/2 介导的组蛋白 3 过度乙酰化增加心脏转录因子的表达。
DOI：
10.1016/j.bbrc.2015.09.090
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发表时间：
2015-10-30
影响因子：
3.1
通讯作者：
Tian, Jie
中科院分区：
文献类型：
--
作者：
Gao, Wenqun;Pan, Bo;Tian, Jie
妊娠期酗酒可能导致胎儿心脏发育异常。我们前期的研究表明，酒精在体内和体外均可诱导组蛋白乙酰化和心脏转录因子的过度表达。本研究旨在探讨ERK 1/2信号通路在酒精诱导的H9 c2细胞组蛋白乙酰化和心脏转录因子上调中的作用。心脏细胞系H9 c2用乙醇培养。采用ERK 1/2信号通路特异性抑制剂U 0126阻断ERK 1/2信号通路。蛋白质印迹分析表明，酒精显着提高磷酸化ERK 1/2的水平，并诱导组蛋白3的高乙酰化，这两个有效地防止与U 0126。实时荧光定量PCR结果显示，U 0126处理显著降低了乙醇诱导的GATA 4和MEF 2c的过表达，降低了GATA 4的基础表达水平，但对MEF 2c无影响。ChIP检测结果显示，U 0126处理显著降低乙醇诱导的组蛋白3在GATA 4和MEF 2c启动子区域附近的高乙酰化。U 0126对GATA 4启动子附近组蛋白3的乙酰化水平也有影响，但对MEF 2c启动子附近组蛋白3的乙酰化水平无影响。这些数据表明，ERK 1/2信号通路在酒精诱导的H9 c2细胞GATA 4和MEF 2c过表达中起重要作用，其机制可能是通过上调基因启动子附近组蛋白3的乙酰化而影响GATA 4和MEF 2c的表达。ERK 1/2信号通路可能是酒精性先天性心脏病的潜在干预靶点。(C)2015 Elsevier Inc. All rights reserved.
Alcohol abuse during pregnancy may cause fetal cardiac developmental abnormalities. Our previous studies showed that alcohol could induce histone hyperacetylation and over-expression of cardiac transcription factors both in vivo and in vitro. The objective of the present study was to investigate the role of ERK1/2 signaling pathway in alcohol-induced histone hyperacetylation and up-regulation of cardiac transcription factors in H9c2 cells. The Cardiac cell line H9c2 was cultured with alcohol. U0126, a specific inhibitor of ERK1/2 pathway was employed to block the ERK1/2 signaling pathway. Western blotting analysis showed that alcohol significantly enhanced the levels of phosphorylated ERK1/2 and induced hyperacetylation of histone3, which were both effectively prevented with U0126. Real-time PCR showed that U0126 treatment significantly decreased alcohol-induced over-expression of GATA4 and MEF2c, and the basal expression level of GATA4, but did not affect MEF2c. ChIP assay showed that U0126 treatment significantly decreased alcohol-induced hyperacetylation of histone3 near the promoter regions of GATA4 and MEF2c. The basal acetylation level of histone3 near the promoter region of GATA4 was affected by U0126 as well, but not that near the promoter region of MEF2c. These data indicated that ERK1/2 signaling played an important role in mediating alcohol induced over-expression of GATA4 and MEF2c, which is possibly through the up-regulation of acetylation of histone3 near the gene promoters that affects the expression of GATA4 and MEF2c in H9c2 cells. ERK1/2 pathway might be a potential target for the intervention of alcohol induced congenital heart diseases. (C) 2015 Elsevier Inc. All rights reserved.