环孢素对耐力运动大鼠骨骼肌Akt及其下游信号分子影响
投稿时间:2010-06-29    点此下载全文
引用本文:廖八根,张仝.环孢素对耐力运动大鼠骨骼肌Akt及其下游信号分子影响[J].医学研究杂志,2010,39(12):63-67
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作者单位
廖八根 广州体育学院运动医学室 
张仝 广州体育学院运动医学室 
基金项目:2008年广东省自然科学基金资助项目(R1003251)
中文摘要: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Western blotting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。
中文关键词:Akt  mTOR  S6K1  GSK-3
 
Effects of Cyclosporin A on Skeletal Muscle Akt and Downstream Signaling Moleucles to Exercise
Abstract:ObjectiveTo explore the effects of calcineurin inhibitor cyclosporin A(CSA) on skeletal muscle Akt/mTOR/S6k1/GSK-3/FoxO1 signaling pathway in response to exercise. MethodsMale 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(Ser473),p-mTOR(Ser2448),P-S6K1(Thr389),GSK-3,FoxO1 were measured by western blotting and GSK-3 activity was measured by isotopic method. ResultsCSA did not affect the basic content of P-Akt(Ser473),p-mTOR(Ser2448),P-S6K1(Thr389) in response to exercise in both SOL and EDL. Exercise increased basic GSK-3 content in EDL, but decreased 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. ConclusionExercise affects skeletal muscle GSK-3 protein and activity and FoxO1 protein content,and CSA can further to increase SOL cytosolic FoxO1 protein content.
keywords:Akt  mTOR  S6K1  GSK-3
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