Effect of branched-chain amino acid supplementation during unloading on regulatory components of protein synthesis in atrophied soleus muscles
Effect of branched-chain amino acid supplementation during unloading on regulatory components of protein synthesis in atrophied soleus muscles
复制标题
DOI：
10.1007/s00421-010-1825-8
复制
发表时间：
2011-08-01
影响因子：
3
通讯作者：
Shimomura, Yoshiharu
中科院分区：
文献类型：
--
作者：
Bajotto, Gustavo;Sato, Yuzo;Shimomura, Yoshiharu
骨骼肌质量的维持依赖于蛋白质合成和蛋白质分解之间的平衡；在卸货过程中功能需求的减少打破了这种平衡，并导致肌肉萎缩。目前的研究分析了卸载比目鱼肌中调节基因和蛋白质的时程变化，以及补充支链氨基酸(BCAA)对肌肉萎缩和调节蛋白质周转的分子丰度的影响。短期(6天)后肢悬吊大鼠后肢肌原纤维蛋白、总RNA和rRNAs显著减少，比目鱼肌明显萎缩。肌肉废弃诱导真核翻译起始因子4E结合蛋白1(4E-BP1)表达上调和丰度增加，两种泛素连接酶(肌肉环指蛋白1和肌肉萎缩F-box蛋白)的基因和蛋白质量增加，细胞周期蛋白D1、核糖体蛋白S6激酶1、哺乳动物雷帕霉素靶标ERK1/2的表达减少。然而，补充支链氨基酸减少了肌原纤维蛋白和RNA的丢失，减缓了4E-BP1的增加，并部分保留了细胞周期蛋白D1、mTOR和ERK1蛋白。这些结果表明，单独补充支链氨基酸并不能阻止蛋白质的降解，但部分保留了特定的信号转导蛋白，这些蛋白在非负重的比目鱼肌中起着蛋白质合成和细胞生长的调节作用。
Maintenance of skeletal muscle mass depends on the equilibrium between protein synthesis and protein breakdown; diminished functional demand during unloading breaks this balance and leads to muscle atrophy. The current study analyzed time-course alterations in regulatory genes and proteins in the unloaded soleus muscle and the effects of branched-chain amino acid (BCAA) supplementation on muscle atrophy and abundance of molecules that regulate protein turnover. Short-term (6 days) hindlimb suspension of rats resulted in significant losses of myofibrillar proteins, total RNA, and rRNAs and pronounced atrophy of the soleus muscle. Muscle disuse induced upregulation and increases in the abundance of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), increases in gene and protein amounts of two ubiquitin ligases (muscle RING-finger protein 1 and muscle atrophy F-box protein), and decreases in the expression of cyclin D1, the ribosomal protein S6 kinase 1, the mammalian target of rapamycin (mTOR), and ERK1/2. BCAA addition to the diet did not prevent muscle atrophy and had no apparent effect on regulators of proteasomal protein degradation. However, BCAA supplementation reduced the loss of myofibrillar proteins and RNA, attenuated the increases in 4E-BP1, and partially preserved cyclin D1, mTOR and ERK1 proteins. These results indicate that BCAA supplementation alone does not oppose protein degradation but partly preserves specific signal transduction proteins that act as regulators of protein synthesis and cell growth in the non-weight-bearing soleus muscle.