The mechanism underlying histone deacetylases regulating cardiac hypertrophy
Lian Ren, Xiushan Wu, Yongqing Li,State Key Lab of Development Biology of Freshwater Fish, Key Laboratory of the Ministry of Education, Heart Development Research Center, College of Life Sciences, Hunan Normal University, Changsha 410081, China
Supported by the National Natural Science Foundation of China No.81470377 Hunan Province Biological Development Engineering and New Product R & D Collaborative Innovation Center No.2013-448-6
作者简介 About authors 任恋,在读博士研究生,专业方向:分子遗传。E-mail:82287168@qq.com。
Abstract Cardiac hypertrophy is a compensatory response that occurs as a result of increased hemodynamic requirement in peripheral tissues. In the process of cardiac hypertrophy, the expression of different types of genes in different stages is transcriptionally regulated by multiple-level physiological and pathological signals. Histone acetylation, as the most extensive post-translational modification, is closely controlled by the antagonistic histone acetyltransferases (HAT) and histone deacetylases (HDACs). Recent studies have shown that HDACs, as a family of enzymes that inhibit transcription and contain highly conserved deacetylase domains, regulate gene expression during cardiac hypertrophy through a variety of pathways. In this review, we mainly summarize the research progress on histone deacetylase in cardiac hypertrophy. By elucidating the role and molecular mechanism of different HDACs in cardiac hypertrophy, it provides new ideas for the treatment of different types of cardiac hypertrophy and heart failure, and molecular targets for new drug design. Keywords:myocardial hypertrophy;post-translational modification;transcription process;histone deacetylases;molecular mechanism
PDF (700KB)元数据多维度评价相关文章导出EndNote|Ris|Bibtex收藏本文 本文引用格式 任恋, 吴秀山, 李永青. 组蛋白去乙酰化酶在调节心肌肥大过程中的作用机制. 遗传[J], 2020, 42(6): 536-547 doi:10.16288/j.yczz.19-346 Lian Ren. The mechanism underlying histone deacetylases regulating cardiac hypertrophy. Hereditas(Beijing)[J], 2020, 42(6): 536-547 doi:10.16288/j.yczz.19-346
HDAC8也被证明可调节心肌肥大。在醋酸去氧皮质酮-盐诱导高血压的大鼠模型中,HDACs抑制剂丙戊酸钠处理使HDAC6和HDAC8的酶活性下降,抑制慢性高血压大鼠的心肌肥大及纤维化[24]。Yan等[25]研究显示miR-21-3p抑制TAC和血管紧张素(angiotensin II, Ang II)诱导的心肌肥大的作用靶点是沉默HDAC8;HDAC8的表达通过提升磷酸化Akt和磷酸化Gsk3β而削弱miR-21-3p介导的心肌肥大抑制作用。Li等 [20] 研究也表明HDAC8和HDAC2在肾性高血压大鼠的心脏重塑中起关键作用。有关I类HDACs调控心肌肥大的相关作用机制见图2。
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