GCN2 deficiency protects mice from denervation-induced skeletal muscle atrophy via inhibiting FoxO3a nuclear translocation

作     者：Yuting Guo Huiwen Wang Yinglong Tang Yue Wang Mengqi Zhang Zhiguang Yang Eric Nyirimigabo Bin Wei Zhongbing Lu Guangju Ji 

作者机构：College of Life Science University of Chinese Academy ofSciences Beijing 100049 China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of Sciences Beijing 100101 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2018年第9卷第11期

页      面：966-970页

核心收录：

学科分类：090603[农学-临床兽医学] 0710[理学-生物学] 07[理学] 09[农学] 0906[农学-兽医学] 071002[理学-动物学] 

基　　金：国家自然科学基金 Chinese Academy of Sciences(Hundred Talents Program) 

摘      要：Dear Editor Several recent clinical studies have indicated that dietary supplementation with branched-chain amino acids （BCAA）, particularly with leucine, is an effective anti-atrophic therapy （Bauer et al., 2015; Tsien et al., 2015; English et al., 2016）. In animal models, BCAA can prevent denervation （Ribeiro et al., 2015）, hindlimb suspension （Maki et al., 2012; Jang et al., 2015） or dexamethasone-induced （Yamamoto et al., 2010） muscle atrophy. General control nonderepressible 2 kinase （GCN2） is a well-known amino-acid sensor. Under conditions of amino-acid deprivation, the increased level of uncharged transfer RNA （tRNA） activates GCN2 through binding to the histadyl-tRNA synthetase-like domain （Wek et al., 1995）. Upon activation, GCN2 phosphorylates eukaryotic initiation factor 2 alpha at Ser51, which leads to translational arrest and restoration of amino acid home- ostasis （Wek et al., 1995; Sood et al., 2000）. As amino acids are potent modulators of protein turnover in skeletal muscle, we proposed that GCN2 may affect denervation-induced muscle atrol0hv, but the detail mechanism remains unclear.