PARP-2 knockdown protects cardiomyocytes from hypertrophy via activation of SIRT1
PARP-2 knockdown protects cardiomyocytes from hypertrophy via activation of SIRT1
复制标题
PARP-2 敲低通过激活 SIRT1 保护心肌细胞免于肥大
DOI：
10.1016/j.bbrc.2012.11.132
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发表时间：
2013-01-18
影响因子：
3.1
通讯作者：
Liu, Peiqing
中科院分区：
文献类型：
--
作者：
Geng, Biao;Cai, Yi;Liu, Peiqing
由多聚（ADP - 核糖）聚合酶（PARPs）催化的多聚（ADP - 核糖）化是一种对蛋白质进行的即时翻译后修饰，其修饰产物是由重复的ADP - 核糖单元构成的同聚链。它参与多种细胞过程，例如细胞存活与死亡、转录、DNA修复以及细胞分裂。据文献记载，PARP抑制剂在不同的病理状况下是有用的。近期，PARP家族的首个成员PARP - 1的激活被发现参与了心肌肥大和心力衰竭的发展及进程。然而，其他PARP在心血管系统中的作用仍有待阐明。PARP - 2在催化结构域上与PARP - 1有69%的相似性，但它们的功能并不完全重叠。在本研究中，我们首次证明PARP - 2参与心肌肥大。在血管紧张素II刺激的大鼠心肌细胞以及承受压力过载的大鼠心脏中，PARP - 2的mRNA和蛋白质水平显著升高。PARP - 2的敲低可保护心肌细胞免于肥大，这可能归因于SIRT1的激活。这些发现为理解PARP - 2相关的心肌病提供了新的视角，并提示PARP - 2抑制剂在心肌肥大中的潜在应用。（C）2012爱思唯尔公司。保留所有权利。
Poly(ADP-ribosyl)ation catalyzed by the poly(ADP-ribose) polymerases (PARPs) is an immediate post-translational modification of proteins with a homopolymeric chain of repeating ADP-ribose units. It is involved in various cellular processes, such as cell survival and death, transcription, DNA repair and cell division. Inhibitors of PARPs have been documented to be useful in different pathological conditions. Recently, activation of PARP-1, the founding member of PARP family, has been revealed to participate in the development and progression of cardiac hypertrophy and heart failure. However, the roles of other PARPs in cardiovascular system remain to be clarified. PARP-2 shares 69% similarity with PARP-1 in catalytic domains, but their functions do not fully overlap. In this study, we show the first evidence that PARP-2 is involved in cardiac hypertrophy. The mRNA and protein levels of PARP-2 were significantly increased in AngII-stimulated rat cardiomyocytes as well as in hearts of rats submitted to pressure overload. PARP-2 knockdown protected cardiomyocytes from hypertrophy, which may be attributed to activation of SIRT1. These findings shed new light on the understanding of PARP-2-related cardiomyopathy, and suggest the potential application of PARP-2 inhibitors in cardiac hypertrophy. (C) 2012 Elsevier Inc. All rights reserved.