Non-sirtuin histone deacetylases in the control of cardiac aging.
Non-sirtuin histone deacetylases in the control of cardiac aging.
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DOI：
10.1016/j.yjmcc.2015.03.010
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发表时间：
2015-06
影响因子：
5
通讯作者：
McKinsey, Timothy A.
中科院分区：
文献类型：
--
作者：
Ferguson, Bradley S.;McKinsey, Timothy A.
组蛋白脱乙酰酶(HDACs)催化核体组蛋白尾部和数千种非组蛋白中赖氨酸残基上的乙酰基的去除。18种哺乳动物的HDAC被分成四类。I、II和IV类HDAC使用锌作为催化活性的辅助因子，而III类HDAC(也称为sirtuins)需要NAD+才能发挥酶功能。锌依赖的HDACs小分子抑制剂在多种压力超负荷和缺血性心肌病的临床前模型中有效，减少病理性肥大和纤维化，改善收缩功能。新的数据揭示了HDAC抑制剂对心脏有益的许多机制，包括抑制氧化应激和炎症，抑制MAP激酶信号转导，增强心肌蛋白质聚集清除和自噬通量。在这里，我们总结了心脏中锌依赖的HDAC和HDAC抑制剂的最新发现，重点介绍了新描述的不同HDAC亚型(例如HDAC2、HDAC3和HDAC6)的功能。还讨论了药物抑制HDAC作为治疗年龄相关性心功能障碍的一种手段的可能性。
Histone deacetylases (HDACs) catalyze removal of acetyl-groups from lysine residues within nucelosomal histone tails and thousands of non-histone proteins. The 18 mammalian HDACs are grouped into four classes. Class I, II and IV HDACs employ zinc as a co-factor for catalytic activity, while class III HDACs (also known as sirtuins) require NAD+ for enzymatic function. Small molecule inhibitors of zinc-dependent HDACs are efficacious in multiple pre-clinical models of pressure overload and ischemic cardiomyopathy, reducing pathological hypertrophy and fibrosis, and improving contractile function. Emerging data have revealed numerous mechanisms by which HDAC inhibitors benefit the heart, including suppression of oxidative stress and inflammation, inhibition of MAP kinase signaling, and enhancement of cardiac protein aggregate clearance and autophagic flux. Here, we summarize recent findings with zinc-dependent HDACs and HDAC inhibitors in the heart, focusing on newly described functions for distinct HDAC isoforms (e.g. HDAC2, HDAC3 and HDAC6). Potential for pharmacological HDAC inhibition as a means of treating age-related cardiac dysfunction is also discussed.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.2
作者：
Fass, Daniel M.;Shah, Rishita;Ghosh, Balaram;Hennig, Krista;Norton, Stephanie;Zhao, Wen-Ning;Reis, Surya A.;Klein, Peter S.;Mazitschek, Ralph;Maglathlin, Rebecca L.;Lewis, Timothy A.;Haggarty, Stephen J.
通讯作者：
Haggarty, Stephen J.
影响因子：
14.8
作者：
Bradner, James E.;West, Nathan;Grachan, Melissa L.;Greenberg, Edward F.;Haggarty, Stephen J.;Warnow, Tandy;Mazitschek, Ralph
通讯作者：
Mazitschek, Ralph
影响因子：
5.6
作者：
Gregoretti, IV;Lee, YM;Goodson, HV
通讯作者：
Goodson, HV
影响因子：
5.3
作者：
de Zoeten, Edwin F.;Wang, Liqing;Hancock, Wayne W.
通讯作者：
Hancock, Wayne W.