Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Nagoya, Japan.
J Appl Physiol (1985). 2020 Apr 1;128(4):830-837. doi: 10.1152/japplphysiol.00578.2019. Epub 2020 Feb 20.
High-intensity muscle contraction (HiMC) is known to induce muscle protein synthesis, a process in which mechanistic target of rapamycin (mTOR) is reported to play a critical role. However, the mechanistic details have not been completely elucidated. Here, we investigated whether Akt plays a role in regulating HiMC-induced mTORC1 activation and muscle protein synthesis using a rodent model of resistance exercise and MK2206 (an Akt kinase inhibitor). The right gastrocnemius muscle of male C57BL/6J mice aged 10 wk was isometrically contracted via percutaneous electrical stimulation (100 Hz, 5 sets of 10 3-s contractions, 7-s rest between contractions, and 3-min rest between sets), while the left gastrocnemius muscle served as a control. Vehicle or MK2206 was injected intraperitoneally 6 h before contraction. MK2206 inhibited both resting and HiMC-induced phosphorylation of Akt1 Ser-473 and Akt2 Ser-474. MK2206 also inhibited the resting phosphorylation of p70S6K and 4E-BP1, which are downstream targets of mTORC1; however, it did not inhibit the HiMC-induced increase in phosphorylation of these targets. Similarly, MK2206 inhibited the resting muscle protein synthesis, but not the resistance exercise-induced muscle protein synthesis. On the basis of these observations, we conclude that although Akt2 regulates resting mTORC1 activity and muscle protein synthesis, HiMC-induced increases in mTORC1 activity and muscle protein synthesis are Akt-independent processes. Akt is well known to be an upstream regulator of mechanistic target of rapamycin (mTOR) and has three isoforms in mammals, namely, Akt1, Akt2, and Akt3. We found that high-intensity muscle contraction (HiMC) increases Akt1 and Akt2 phosphorylation; however, HiMC-induced increases in mTORC1 activity and muscle protein synthesis are Akt-independent processes.
高强度肌肉收缩（HiMC）已知可诱导肌肉蛋白质合成，这一过程中雷帕霉素靶蛋白（mTOR）被报道起着关键作用。然而，其具体机制尚未完全阐明。在这里，我们使用抗阻运动的啮齿动物模型和 MK2206（一种 Akt 激酶抑制剂）研究了 Akt 是否在调节 HiMC 诱导的 mTORC1 激活和肌肉蛋白质合成中发挥作用。10 周龄雄性 C57BL/6J 小鼠的右比目鱼肌通过经皮电刺激（100 Hz，5 组 10 个 3 秒收缩，收缩之间休息 7 秒，组间休息 3 分钟）进行等长收缩，而左比目鱼肌作为对照。在收缩前 6 小时，腹腔内注射载体或 MK2206。MK2206 抑制 Akt1 Ser-473 和 Akt2 Ser-474 的静息和 HiMC 诱导磷酸化。MK2206 还抑制 mTORC1 的下游靶点 p70S6K 和 4E-BP1 的静息磷酸化；然而，它并没有抑制这些靶点的 HiMC 诱导的磷酸化增加。同样，MK2206 抑制静息肌肉蛋白质合成，但不抑制抗阻运动引起的肌肉蛋白质合成。基于这些观察结果，我们得出结论，尽管 Akt2 调节静息状态下的 mTORC1 活性和肌肉蛋白质合成，但 HiMC 诱导的 mTORC1 活性和肌肉蛋白质合成的增加是 Akt 非依赖性过程。Akt 是众所周知的雷帕霉素靶蛋白（mTOR）的上游调节剂，在哺乳动物中有 3 种同工型，即 Akt1、Akt2 和 Akt3。我们发现，高强度肌肉收缩（HiMC）增加 Akt1 和 Akt2 的磷酸化；然而，HiMC 诱导的 mTORC1 活性和肌肉蛋白质合成的增加是 Akt 非依赖性过程。
