Graduate Program in Physiological Sciences, Federal University of Sergipe, São Cristóvão, SE, Brazil; Department of Physiology, Center for Biological and Health Sciences, Federal University of Sergipe, São Cristóvão, SE, Brazil.
Department of Physiology, Center for Biological and Health Sciences, Federal University of Sergipe, São Cristóvão, SE, Brazil.
Life Sci. 2021 Aug 15;279:119665. doi: 10.1016/j.lfs.2021.119665. Epub 2021 Jun 2.
Although it is well established that skeletal muscle contains oxytocin (OT) receptors and OT-knockout mice show premature development of sarcopenia, the role of OT in controlling skeletal muscle mass is still unknown. Therefore, the present work aimed to determine OT's effects on skeletal muscle protein metabolism.
Total proteolysis, proteolytic system activities and protein synthesis were assessed in isolated soleus muscle from prepubertal female rats. Through in vivo experiments, rats received 3-day OT treatment (3UI.kg.day, i.p.) or saline, and muscles were harvested for mass-gain assessment.
In vitro OT receptor stimulation reduced total proteolysis, specifically through attenuation of the lysosomal and proteasomal proteolytic systems, and in parallel activated the Akt/FoxO1 signaling and suppressed atrogenes (e.g., MuRF-1 and atrogin-1) expression induced by motor denervation. On the other hand, the protein synthesis was not altered by in vitro treatment with the OT receptor-selective agonist. Although short-term OT treatment did not change the atrogene mRNA levels, the protein synthesis was stimulated, resulting in soleus mass gain, probably through an indirect effect.
Taken together, these data show for the first time that OT directly inhibits the proteolytic activities of the lysosomal and proteasomal systems in rat oxidative skeletal muscle by suppressing atrogene expression via stimulation of Akt/FoxO signaling. Moreover, the data obtained from in vivo experiments suggest OT's ability to control rat oxidative skeletal muscle mass.
尽管已经证实骨骼肌含有催产素（OT）受体，OT 敲除小鼠表现出骨骼肌减少症的过早发展，但 OT 控制骨骼肌质量的作用仍不清楚。因此，本研究旨在确定 OT 对骨骼肌蛋白代谢的影响。
评估来自青春期前雌性大鼠的分离比目鱼肌中的总蛋白水解、蛋白水解系统活性和蛋白质合成。通过体内实验，大鼠接受了 3 天 OT 治疗（3UI.kg.day，腹腔注射）或生理盐水，并收获肌肉进行质量增加评估。
OT 受体刺激在体外减少了总蛋白水解，特别是通过衰减溶酶体和蛋白酶体蛋白水解系统，并平行激活 Akt/FoxO1 信号通路并抑制运动神经元损伤诱导的自噬基因（例如 MuRF-1 和 atrogin-1）表达。另一方面，OT 受体选择性激动剂的体外处理并没有改变蛋白质合成。尽管短期 OT 处理没有改变自噬基因 mRNA 水平，但蛋白质合成受到刺激，导致比目鱼肌质量增加，可能是通过间接作用。
综上所述，这些数据首次表明，OT 通过刺激 Akt/FoxO 信号通路抑制自噬基因表达，直接抑制大鼠氧化骨骼肌中溶酶体和蛋白酶体系统的蛋白水解活性。此外，体内实验获得的数据表明 OT 能够控制大鼠氧化骨骼肌的质量。
