Hayasaka Miki, Tsunekawa Haruka, Yoshinaga Mariko, Murakami Taro
Department of Nutrition, Shigakkan University, Yokone-Machi, Ohbu, Japan.
Physiol Rep. 2014 Dec 24;2(12). doi: 10.14814/phy2.12254. Print 2014 Dec 1.
Working muscle conserves adenosine triphosphate (ATP) for muscle contraction by attenuating protein synthesis through several different pathways. Regulated in development and DNA damage response 1 (REDD1) is one candidate protein that can itself attenuate muscle protein synthesis during muscle contraction. In this study, we investigated whether endurance exercise induces REDD1 expression in association with decreased mammalian target of rapamycin (mTOR) complex I (mTORC1) signaling and global protein synthesis in rat skeletal muscle. After overnight fasting, rats ran on a treadmill at a speed of 28 m/min for 60 min, and were killed before and immediately, 1, 3, 6, 12, and 24 h after exercise. REDD1 mRNA and corresponding protein levels increased rapidly immediately after exercise, and gradually decreased back to the basal level over a period of 6 h in the gastrocnemius muscle. Phosphorylation of mTOR Ser2448 and S6K1 Thr389 increased with the exercise, but diminished in 1-3 h into the recovery period after cessation of exercise. The rate of protein synthesis, as determined by the surface sensing of translation (SUnSET) method, was not altered by exercise in fasted muscle. These results suggest that REDD1 attenuates exercise-induced mTORC1 signaling. This may be one mechanism responsible for blunting muscle protein synthesis during exercise and in the early postexercise recovery period.
工作中的肌肉通过几种不同途径减弱蛋白质合成来保存三磷酸腺苷（ATP）以供肌肉收缩。发育和DNA损伤反应调节因子1（REDD1）是一种候选蛋白，其本身可在肌肉收缩期间减弱肌肉蛋白质合成。在本研究中，我们调查了耐力运动是否会诱导大鼠骨骼肌中REDD1表达，并伴有哺乳动物雷帕霉素靶蛋白（mTOR）复合体I（mTORC1）信号传导及整体蛋白质合成的降低。过夜禁食后，大鼠在跑步机上以28米/分钟的速度跑60分钟，并在运动前、运动后立即、1、3、6、12和24小时处死。运动后立即，腓肠肌中REDD1 mRNA和相应蛋白水平迅速升高，并在6小时内逐渐降至基础水平。mTOR Ser2448和S6K1 Thr389的磷酸化随运动增加，但在运动停止后的恢复期1 - 3小时内减弱。通过翻译表面传感（SUnSET）方法测定的蛋白质合成速率在禁食肌肉中不受运动影响。这些结果表明，REDD1减弱运动诱导的mTORC1信号传导。这可能是运动期间及运动后早期恢复期肌肉蛋白质合成减弱的一种机制。
