Eukaryotic initiation factor 2B epsilon induces cap-dependent translation and skeletal muscle hypertrophy
Eukaryotic initiation factor 2B epsilon induces cap-dependent translation and skeletal muscle hypertrophy
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DOI：
10.1113/jphysiol.2010.202432
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发表时间：
2011-06-15
影响因子：
5.5
通讯作者：
Bamman, Marcas M.
中科院分区：
文献类型：
--
作者：
Mayhew, David L.;Hornberger, Troy A.;Bamman, Marcas M.
本研究的目的是确定已知控制骨骼肌中对机械负荷有反应的mRNA翻译起始的信号传导组分，并可能部分导致肌纤维肥大。为了实现这一点，我们首先利用了人类集群模型，其中骨骼肌样本的对象有很大的分歧肥大反应阻力训练用于识别与肌纤维肥大的程度相关的信号蛋白。我们发现，11个翻译信号分子检查，p（T421/S424）-p70 S6 K磷酸化和总真核生物起始因子2B β（eIF 2B β）蛋白丰度的反应后，一轮不习惯的阻力运动与肌纤维肥大16周的训练。后续研究显示，单独过表达eIF 2B β在体外足以诱导L 6成肌细胞中帽依赖性翻译增加87%，在体内足以诱导小鼠骨骼肌中肌纤维肥大21%（P < 0.05）。然而，基因改变p70 S6 K活性对体内小鼠骨骼肌或体外多个细胞系中eIF 2B α蛋白丰度没有影响（P > 0.05），表明这两种现象没有直接关系。这些是第一个数据，机械联系eIF 2B β丰度的骨骼肌纤维肥大，并表明eIF 2B β丰度可能至少部分地在人类骨骼肌暴露于机械刺激的广泛不同的肥大表型的基础。
The purpose of this study was to identify signalling components known to control mRNA translation initiation in skeletal muscle that are responsive to mechanical load and may be partly responsible for myofibre hypertrophy. To accomplish this, we first utilized a human cluster model in which skeletal muscle samples from subjects with widely divergent hypertrophic responses to resistance training were used for the identification of signalling proteins associated with the degree myofibre hypertrophy. We found that of 11 translational signalling molecules examined, the response of p(T421/S424)-p70S6K phosphorylation and total eukaryotic initiation factor 2B epsilon (eIF2B epsilon) protein abundance after a single bout of unaccustomed resistance exercise was associated with myofibre hypertrophy following 16 weeks of training. Follow up studies revealed that overexpression of eIF2B epsilon alone was sufficient to induce an 87% increase in cap-dependent translation in L6 myoblasts in vitro and 21% hypertrophy of myofibres in mouse skeletal muscle in vivo (P < 0.05). However, genetically altering p70S6K activity had no impact on eIF2B epsilon protein abundance in mouse skeletal muscle in vivo or multiple cell lines in vitro (P > 0.05), suggesting that the two phenomena were not directly related. These are the first data that mechanistically link eIF2B epsilon abundance to skeletal myofibre hypertrophy, and indicate that eIF2B epsilon abundance may at least partially underlie the widely divergent hypertrophic phenotypes in human skeletal muscle exposed to mechanical stimuli.