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大鼠比目鱼肌对下肢去负荷后离心收缩的合成信号反应:牵张激活离子通道的潜在作用。

An Anabolic Signaling Response of Rat Soleus Muscle to Eccentric Contractions Following Hindlimb Unloading: A Potential Role of Stretch-Activated Ion Channels.

机构信息

Myology Laboratory, Institute of Biomedical Problems RAS, 123007, 76A Khoroshevskoe shosse, 123007 Moscow, Russia.

出版信息

Int J Mol Sci. 2019 Mar 7;20(5):1165. doi: 10.3390/ijms20051165.

Abstract

Mechanisms that convert a mechanical signal into a biochemical response in an atrophied skeletal muscle remain poorly understood. The aims of the study were to evaluate a temporal response of anabolic signaling and protein synthesis (PS) to eccentric contractions (EC) in rat soleus during hindlimb unloading (HU); and to assess a possible role of stretch-activated ion channels (SAC) in the propagation of a mechanical signal to mTORC1 following HU. Following HU, an isolated soleus was subjected to EC. Upon completion of EC, muscles were collected for western blot analyses to determine the content/phosphorylation of the key anabolic markers. We found that a degree of EC-induced p70S6K phosphorylation and the rate of PS in the soleus of 3- and 7-day unloaded rats was significantly less than that in control. A decrease in EC-induced phosphorylation of p70S6K, RPS6 and PS in the 7-day unloaded soleus treated with SAC inhibitor did not differ from that of the 7-day unloaded soleus without SAC blockade. The results of the study suggest that (i) HU results in a blunted anabolic response to a bout of EC, (ii) attenuation of mTORC1-signaling and PS in response to EC in unloaded soleus may be associated with inactivation of SAC.

摘要

在萎缩的骨骼肌中,将机械信号转换为生化反应的机制仍知之甚少。本研究的目的是评估在下肢去负荷(HU)期间大鼠比目鱼肌中离心收缩(EC)对合成代谢信号和蛋白质合成(PS)的时间反应;并评估 SAC 在 HU 后将机械信号传播到 mTORC1 中的可能作用。HU 后,将分离的比目鱼肌进行 EC。完成 EC 后,收集肌肉进行 Western blot 分析,以确定关键合成代谢标记物的含量/磷酸化。我们发现,在 3 天和 7 天去负荷大鼠的比目鱼肌中,EC 诱导的 p70S6K 磷酸化程度和 PS 速率明显低于对照组。在 SAC 抑制剂处理的 7 天去负荷比目鱼肌中,EC 诱导的 p70S6K、RPS6 和 PS 磷酸化减少与没有 SAC 阻断的 7 天去负荷比目鱼肌没有差异。研究结果表明:(i)HU 导致 EC 对一系列反应的合成代谢反应减弱,(ii)在去负荷比目鱼肌中,EC 引起的 mTORC1 信号和 PS 衰减可能与 SAC 失活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3405/6429234/c90f363dc810/ijms-20-01165-g001.jpg

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