REDD1 attenuates cardiac hypertrophy via enhancing autophagy
REDD1 attenuates cardiac hypertrophy via enhancing autophagy
复制标题
REDD1 通过增强自噬来减轻心脏肥大。
DOI：
10.1016/j.bbrc.2014.10.079
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发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Dong, Yugang
中科院分区：
文献类型：
--
作者：
Liu, Chen;Xue, Ruicong;Dong, Yugang
心肌肥厚是心血管疾病发病率和死亡率的主要危险因素。自噬被证实参与调节心肌肥厚。Redd1是一种应激反应蛋白，已被证明在自噬诱导中起作用。然而，Redd1在心肌肥厚中的作用仍不清楚。我们的研究表明，RNAi下调Redd1基因可加重苯肾上腺素(PE)诱导的心肌肥厚，表现为心钠素和细胞表面积等肥大标志物的增加。此外，我们还发现ERK1/2信号通路参与了Redd1的肥大效应。此外，我们的研究表明，Redd1基因敲除会损害肥大心肌细胞的自噬。自噬诱导信号分子mTOR被PE胁迫下Redd1基因的敲除激活。重要的是，自噬增强剂雷帕霉素显著逆转了Redd1基因敲除的促肥大效应。综上所述，我们首先证明了Redd1是通过增强自噬来抑制心肌肥厚所必需的。(C)2014 Elsevier Inc.保留所有权利。
Cardiac hypertrophy is a major risk factor of cardiovascular morbidity and mortality. Autophagy is established to be involved in regulating cardiac hypertrophy. REDD1, a stress-responsive protein, is proved to contribute in autophagy induction. However, the role of REDD1 in cardiac hypertrophy remains unknown. Our study demonstrated that REDD1 knockdown by RNAi exacerbated phenylephrine (PE)-induced cardiac hypertrophy, manifested by increased hypertrophic markers such as ANP and cell surface area. In addition, we discovered that ERK1/2 signaling pathway was involved in the effect of REDD1 on hypertrophy. Moreover, our study showed that REDD1 knockdown impaired autophagy in hypertrophied cardiomyocytes. mTOR, a signaling molecule governing autophagy induction, was activated by the knock-down of REDD1 under PE stress. Importantly, the pro-hypertrophic effect of REDD1 knockdown was significantly reversed by the autophagy enhancer rapamycin. Taken together, we firstly prove that REDD1 is essential for inhibiting cardiac hypertrophy by enhancing autophagy. (C) 2014 Elsevier Inc. All rights reserved.