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; ...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.展开更多
文摘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.
