Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis
Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis
复制标题
肌肉生长抑制素通过调节 AMPK 抑制 eEF2K-eEF2 抑制蛋白质合成
DOI：
10.1016/j.bbrc.2017.10.040
复制
发表时间：
2017-12-09
影响因子：
3.1
通讯作者：
Wei, Hong-Kui
中科院分区：
文献类型：
--
作者：
Deng, Zhao;Luo, Pei;Wei, Hong-Kui
骨骼肌的生长依赖于蛋白质合成，而蛋白质合成速率主要在翻译起始和延伸阶段受到调控。肌肉生长抑制素（Myostatin）是转化生长因子-β（TGF-β）超家族的成员，是蛋白质合成的负调控因子。将C2C12肌管分别与0、0.01、0.1、1、2、3微克/毫升的肌肉生长抑制素重组蛋白一起孵育，然后我们采用SUnSET方法检测蛋白质合成速率。我们发现，高浓度的肌肉生长抑制素（2微克/毫升和3微克/毫升）通过阻断哺乳动物雷帕霉素靶蛋白（mTOR）和真核延伸因子2激酶 - 真核延伸因子2（eEF2K - eEF2）通路来抑制蛋白质合成，而低浓度的肌肉生长抑制素（0.01、0.1和1微克/毫升）则通过调节eEF2K - eEF2通路活性来阻断蛋白质合成，且不影响mTOR通路，此外，肌肉生长抑制素通过调节5'-腺苷酸活化蛋白激酶（AMPK）通路来抑制eEF2K - eEF2通路，从而抑制蛋白质合成。这为肌肉生长抑制素调节蛋白质合成及治疗肌肉萎缩提供了一种新机制。（C）2017爱思唯尔公司出版
Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-beta (TGF-beta) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 mu g/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 mu g/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 mu g/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy. (C) 2017 Published by Elsevier Inc.