Myology Laboratory, Institute of Biomedical Problems RAS, Moscow, Russia.
INSERM U1059, Integrative Biology of Bone Tissue Laboratory, Lyon University, St.- Etienne, France.
Sci Rep. 2017 Jun 14;7(1):3514. doi: 10.1038/s41598-017-03758-x.
The purpose of the study was to assess the rate of protein synthesis (PS) and elucidate signalling pathways regulating PS in mouse soleus (Sol) and tibialis anterior (TA) muscles following chronic hypergravity (30-day centrifugation at 2G). The content of the key signalling proteins of the various anabolic signalling pathways was determined by Western-blotting. The rate of PS was assessed using in-vivo SUnSET technique. An exposure to 2G centrifugation did not induce any significant changes in the rate of PS as well as phosphorylation status of the key anabolic markers (AKT, p70s6k, 4E-BP1, GSK-3beta, eEF2) in Sol. On the contrary, a significant 55% increase in PS (p < 0.05) was found in TA. The cause of such a rise in PS could be associated with an increase in AKT (+72%, p < 0.05), GSK-3beta (+60%, p < 0.05) and p70s6k (+40%, p < 0.05) phosphorylation, as well as a decrease in eEF2 phosphorylation (-46%, p < 0.05) as compared to control values. Thus, the results of our study indicate that 30-day 2G centrifugation induces a distinct anabolic response in mouse Sol and TA muscles. The activation of the PS rate in TA could be linked to an up-regulation of both mTORC1-dependent and mTORC1-independent signalling pathways.
这项研究的目的是评估蛋白质合成(PS)的速率,并阐明在慢性超重力(2G 离心 30 天)后调节小鼠比目鱼肌(Sol)和胫骨前肌(TA)肌肉中 PS 的信号通路。通过 Western-blotting 确定各种合成代谢信号通路的关键信号蛋白的含量。使用体内 SUnSET 技术评估 PS 速率。暴露于 2G 离心不会引起 PS 速率以及 Sol 中关键合成代谢标志物(AKT、p70s6k、4E-BP1、GSK-3β、eEF2)的磷酸化状态发生任何显著变化。相反,在 TA 中发现 PS 增加了 55%(p<0.05)。PS 增加的原因可能与 AKT(增加 72%,p<0.05)、GSK-3β(增加 60%,p<0.05)和 p70s6k(增加 40%,p<0.05)的磷酸化增加以及 eEF2 磷酸化减少(减少 46%,p<0.05)有关,与对照值相比。因此,我们的研究结果表明,30 天 2G 离心在小鼠 Sol 和 TA 肌肉中引起明显的合成代谢反应。TA 中 PS 速率的激活可能与 mTORC1 依赖性和 mTORC1 非依赖性信号通路的上调有关。