...
首页> 外文期刊>Clinical and experimental pharmacology & physiology >Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation
【24h】

Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation

机译:心力衰竭和血管紧张素II调节心房Pitx2c启动子甲基化

获取原文
获取原文并翻译 | 示例
           

摘要

Heart failure (HF) can increase atrial fibrillation and induce cardiac hypermethylation. The homeobox gene Pitx2c plays important roles in the genesis of atrial fibrillation and the promoter region of Pitx2c contains cytosine-phosphate-guanine islands. Therefore, epigenetic modification by hypermethylation may reduce Pitx2c expression in atrial myocytes. The aim of the present study were to evaluate whether HF can modulate DNA methylation of Pitx2c and the potential mechanisms involved. We used real-time polymerase chain reaction, immunoblotting and pyrosequencing to investigate RNA and protein expression, as well as the methylation of Pitx2c, in isoproterenol-induced HF, healthy rat left atria and in HL-1 cells with and without (control) exposure to angiotensin (Ang) II (0.1 and 1 μmol/L) or isoproterenol (1 or 10 μmol/L) for 24 h. The HF atrium exhibited increased Pitx2c promoter methylation with increased DNA methyltransferase (DNMT) 1 and decreased Pitx2c protein levels compared with the normal atrium. Angiotensin II (0.1 and 1 μmol/L), increased Pitx2c promoter methylation in HL-1 cells with increased DNMT1 and decreased Pitx2c and Kir2.1 protein levels compared with control cells. These effects were attenuated by the methylation inhibitor 5-aza-2′-deoxycytidine (0.1 μmol/L) and by the AngII receptor blocker losartan (10 μmol/L). However, isoproterenol (1 and 10 μmol/L) did not change the expression of the Pitx2c, DNMT1 and Kir2.1 proteins. In conclusion, HF induces Pitx2c promoter hypermethylation and AngII may contribute to the hypermethylation in HF.
机译:心力衰竭(HF)可增加心房纤颤并诱发心脏甲基化过度。同源盒基因Pitx2c在心房纤颤的发生中起重要作用,Pitx2c的启动子区域包含胞嘧啶-磷酸-鸟嘌呤岛。因此,通过高甲基化的表观遗传修饰可能会降低心房肌细胞中Pitx2c的表达。本研究的目的是评估HF是否可以调节Pitx2c的DNA甲基化及其潜在的机制。我们使用实时聚合酶链反应,免疫印迹和焦磷酸测序技术研究了异丙肾上腺素诱导的心衰,健康大鼠左心房以及有或没有(对照)暴露的HL-1细胞中的RNA和蛋白质表达以及Pitx2c的甲基化至血管紧张素II(0.1和1μmol/ L)或异丙肾上腺素(1或10μmol/ L)24小时。与正常中庭相比,HF中庭显示增加的Pitx2c启动子甲基化,同时增加DNA甲基转移酶(DNMT)1并降低Pitx2c蛋白水平。与对照组相比,血管紧张素II(0.1和1μmol/ L)在HL-1细胞中增加了Pitx2c启动子甲基化,而DNMT1增加,而Pitx2c和Kir2.1蛋白水平降低了。甲基化抑制剂5-氮杂2'-脱氧胞苷(0.1μmol/ L)和AngII受体阻滞剂氯沙坦(10μmol/ L)减弱了这些作用。但是,异丙肾上腺素(1和10μmol/ L)不会改变Pitx2c,DNMT1和Kir2.1蛋白的表达。总之,HF诱导Pitx2c启动子过度甲基化,而AngII可能有助于HF中的过度甲基化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号