Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin, 300070, China.
Department of Anatomy and Histology, School of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China.
Exp Cell Res. 2023 Nov 1;432(1):113779. doi: 10.1016/j.yexcr.2023.113779. Epub 2023 Sep 12.
It has long been recognized that resistance exercise can substantially increase skeletal muscle mass and strength, but whether it can protect against glucocorticoid-induced muscle atrophy and its potential mechanism is yet to be determined. This study aimed to investigate the protective effects of resistance exercise in dexamethasone-induced muscle atrophy and elucidate the possible function of exercise-induced protein Sestrin2 in this process.
Eight-week-old male C57BL/6J mice carried out the incremental mouse ladder exercise for 11 weeks. Two weeks before the end of the intervention, mice were daily intraperitoneally injected with dexamethasone. Body composition, muscle mass, and exercise performance were examined to evaluate muscle atrophy. In vitro, C2C12 cells were used for RT-qPCR, Western Blot, and immunofluorescence experiments to elucidate the potential mechanism.
Our results showed that long-term resistance exercise is an effective intervention for dexamethasone-induced muscle atrophy. We also found that Sestrin2 plays a vital role in dexamethasone-induced muscle atrophy. In both animal (P = .0006) and cell models (P = .0266), dexamethasone intervention significantly reduced the protein expression of Sestrin2, which was increased (P = .0112) by resistance exercise. Inversely, overexpression of Sestrin2 improved (P < .0001) dexamethasone-induced myotube cell atrophy by reducing the activation of the ubiquitin-proteasome pathway via inhibiting Forkhead box O3 (FoxO3a) and myostatin (MSTN)/small mother against decapentaplegic (Smad) signaling pathways.
Taken together, our results indicated that Sestrin2 may serve as an effective molecule that mimics the protective effect of resistance exercise on dexamethasone-induced muscle atrophy.
长期以来，人们一直认识到抗阻运动可以显著增加骨骼肌质量和力量，但它是否能预防糖皮质激素诱导的肌肉萎缩及其潜在机制尚待确定。本研究旨在探讨抗阻运动对地塞米松诱导的肌肉萎缩的保护作用，并阐明运动诱导的 Sestrin2 在这一过程中的可能作用。
8 周龄雄性 C57BL/6J 小鼠进行递增式小鼠梯运动 11 周。在干预结束前 2 周，小鼠每天腹腔内注射地塞米松。检测身体成分、肌肉质量和运动表现，以评估肌肉萎缩。体外，使用 C2C12 细胞进行 RT-qPCR、Western Blot 和免疫荧光实验，以阐明潜在机制。
我们的结果表明，长期抗阻运动是预防地塞米松诱导肌肉萎缩的有效干预措施。我们还发现 Sestrin2 在地塞米松诱导的肌肉萎缩中起着至关重要的作用。在动物（P=0.0006）和细胞模型中（P=0.0266），地塞米松干预显著降低了 Sestrin2 的蛋白表达，而抗阻运动则增加了 Sestrin2 的蛋白表达（P=0.0112）。相反，Sestrin2 的过表达通过抑制叉头框 O3（FoxO3a）和肌肉生长抑制素（MSTN）/小 Smad 信号通路，减少了泛素-蛋白酶体途径的激活，改善了地塞米松诱导的肌管细胞萎缩（P<0.0001）。
综上所述，我们的结果表明，Sestrin2 可能作为一种有效的分子，模拟抗阻运动对地塞米松诱导的肌肉萎缩的保护作用。
