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The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

组蛋白去甲基化酶 JMJD1C 调节 CAMKK2-AMPK 信号参与心肌肥厚

  • 影响因子:3.22
  • DOI:10.3389/fphys.2020.00539
  • 作者列表:"Shuang Yu","Yihong Li","Hongwei Zhao","Qingdong Wang","Ping Chen
  • 发表时间:2020-06-18
Abstract

The roles of the histone demethylase JMJD1C in cardiac hypertrophy remain unknown. JMJD1C was overexpressed in hypertrophic hearts of humans and mice, whereas the histone methylation was reduced. Jmjd1c knockdown repressed the angiotensin II (Ang II)-mediated increase in cardiomyocyte size and overexpression of hypertrophic genes in cardiomyocytes. By contrast, JMJD1C overexpression promoted the hypertrophic response of cardiomyocytes. Our further molecular mechanism study revealed that JMJD1C regulated AMP-dependent kinase (AMPK) in cardiomyocytes. JMJD1C did not influence LKB1 but repressed Camkk2 expression in cardiomyocytes. Inhibition of CAMKK2 with STO609 blocked the effects of JMJD1C on AMPK. AMPK knockdown blocked the inhibitory functions of JMJD1C knockdown on Ang II-induced hypertrophic response, whereas metformin reduced the functions of JMJD1C and repressed the hypertrophic response in cardiomyocytes.

摘要

组蛋白去甲基化酶 JMJD1C 在心肌肥厚中的作用仍然未知。JMJD1C 在人和小鼠的肥大心脏中过表达,而组蛋白甲基化减少。Jmjd1c 敲除抑制血管紧张素 ⅱ (Ang ⅱ) 介导的心肌细胞大小增加和心肌细胞肥大基因的过度表达。相比之下,JMJD1C 过表达促进了心肌细胞的肥大反应。我们进一步的分子机制研究揭示了 JMJD1C 调控心肌细胞中 AMP 依赖性激酶 (AMPK)。JMJD1C 不影响 LKB1,但抑制心肌细胞 Camkk2 的表达。用 STO609 抑制 CAMKK2 阻断 JMJD1C 对 AMPK 的影响。AMPK 敲除阻断了 JMJD1C 敲除对 Ang II 诱导的心肌肥厚反应的抑制功能,而二甲双胍降低了 JMJD1C 的功能,抑制了心肌细胞的肥厚反应。

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DOI:10.1186/s12872-019-01311-4
作者列表:["Nattawut Wongpraparut","Sarawut Siwamogsatham","Tomorn Thongsri","Pornchai Ngamjanyaporn","Arintaya Phrommintikul","Kompoj Jirajarus","Tarinee Tangcharoen","Kid Bhumimuang","Pinij Kaewsuwanna","Rungroj Krittayaphong","Rungtiwa Pongakasira","Harvey D. White"]

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影响因子:4.69
发表时间:2020-01-07
DOI:10.1186/s12968-019-0590-z
作者列表:["Yao-Dan Liang","Yuan-Wei Xu","Wei-Hao Li","Ke Wan","Jia-Yu Sun","Jia-Yi Lin","Qing Zhang","Xiao-Yue Zhou","Yu-Cheng Chen"]

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影响因子:4.69
发表时间:2020-01-05
DOI:10.1186/s12968-019-0589-5
作者列表:["Yingxia Yang","Gang Yin","Yong Jiang","Lei Song","Shihua Zhao","Minjie Lu"]

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