Posttranslational modifications of histone deacetylases: Implications for cardiovascular diseases

被引:76
作者
Eom, Gwang Hyeon
Kook, Hyun [1 ]
机构
[1] Chonnam Natl Univ, Sch Med, Dept Pharmacol, Kwangju 501746, South Korea
基金
新加坡国家研究基金会;
关键词
Histone deacetylases; Cardiovascular diseases; Posttranslational modifications; Histone deacetylase inhibitors; Therapeutics; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; CARDIAC MYOCYTE PROLIFERATION; DEPENDENT NUCLEAR EXPORT; GENE-EXPRESSION; CLASS-I; ENDOTHELIAL-CELLS; HYPERTROPHIC RESPONSE; LYSINE ACETYLATION;
D O I
10.1016/j.pharmthera.2014.02.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Posttranslational modification (PTM) is a term that implies dynamic modification of proteins after their translation. PTM is involved not only in homeostasis but also in pathologic conditions related to diverse diseases. Histone deacetylases (HDACs), which are known as transcriptional regulators, are one example of posttranslational modifiers with diverse roles in human pathophysiology, including cardiovascular diseases. In experimental models, HDAC inhibitors are beneficial in supraventricular arrhythmia, myocardial infarction, cardiac remodeling, hypertension, and fibrosis. In addition, HDACs are closely related to other vascular diseases such as neointima formation, atherosclerosis, and vascular calcification. Currently, HDACs are classified into four different classes. The class Ha HDACs work as transcriptional regulators mainly by direct association with other transcription factors to their target binding elements in a phosphorylation-dependent manner. Class I HDACs, by contrast, have much greater enzymatic activity than the class II HDACs and target various non-histone proteins as well as the histone-core complex. Class I HDACs undergo PTMs such as phosphorylation, sumoylation, and S-nitrosylation. Considering the growing evidence for the role of HDACs in cardiovascular diseases, the PTMs of the HDACs themselves as well as HDAC-mediated PTM of their targets should be considered for future potential therapeutic targets. In this review, we discuss 1) the roles of each HDAC in specific cardiovascular diseases and 2) the PTM of HDACs, 3) and the implications of such modifications for cardiovascular diseases. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:168 / 180
页数:13
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