环孢素对耐力运动大鼠骨骼肌Akt及其下游信号分子影响

Effects of Cyclosporin A on Skeletal Muscle Akt and Downstream Signaling Moleucles to Exercise

目的本研究旨在探讨耐力运动时骨骼肌Akt/mTOR/S6k1/GSK-3/FoxO1信号通路变化及钙调神经磷酸酶(CaN)抑制剂环孢素(CSA)是否影响这些信号分子。方法雄性SD大鼠随机分成对照组、运动组和CSA+运动组,6周实验结束取比目鱼肌(SOL)和趾长伸肌(EDL),用W estern b lotting法测基础P-Akt(Ser473)、p-mTOR(Ser2448)、P-S6K1(Thr389)和GSK-3、FoxO1蛋白含量,并用放射性核素法测GSK-3活性。结果 CSA不影响耐力运动大鼠SOL和EDL基础胞质P-Akt(Ser473)、p-mTOR(Ser2448)、P-S6K1(Thr389)含量;耐力运动增加EDL胞质GSK-3蛋白含量,但降低其活性;CSA不影响耐力运动诱导的EDL GSK-3蛋白含量和活性变化。耐力运动增加SOL FoxO1蛋白含量,CSA进一步增加其胞质含量,但CSA不影响SOL、EDL胞核FoxO1含量。结论耐力运动可影响骨骼肌静息GSK-3蛋白含量和活性以及FoxO1蛋白含量,CSA进一步增加耐力运动时大鼠SOL胞质FoxO1蛋白。

Objective To explore the effects of calcincurin inhibitor cyclosporin A （CSA） on skeletal muscle Akt/mTOR/S6kl/ GSK -3/FoxOl signaling pathway in response to exercise. Methods Male SD rats were randomized into 3 groups：control group,exercise group, CSA ＋ exercise group. After experiment, soleus（SOL） and extensor digitorum longus （EDL）muscle were removed for analysis. Basic protein content of P - Akt （ Set473 ） , p - mTOR （ Ser2＊4s ） , P - S6K1 （ Thr3a9 ） , GSK - 3, FoxO1 were measured by western blotting and GSK - 3 activity was measured by isotopic method. Results CSA did not affect the basic content of P - Akt （ Ser473 ） , p - mTOR （ Ser244s ） ,P - S6KI （Thr389 ） in response to exercise in both SOL and EDL. Exercise increased basic GSK - 3 content in EDL, but de- creased GSK -3 activity. CSA did not regulate exercise -induced change of GSK -3 in EDL. Exercise increased FoxO1 protein content, and CSA furthered to increase it in SOl,, but CSA did not affect nuclear FoxO1 protein content in SOL and EDL. Conclusion Exercise affects skeletal muscle GSK -3 protein and activity and FoxOl protein content,and CSA can further to increase SOL cytosolic FoxO1 protein content.