急性低氧对大鼠骨骼肌AMPK/TSC2/mTOR信号的影响
首发时间:2013-01-04
摘要:目的:通过急性低氧暴露,观察复氧后骨骼肌LKB1、AMP/ATP、AMPK以及mTOR信号时程变化规律,探索低氧经该信号通路下调骨骼肌蛋白合成的作用机制。方法:8周龄雄性SD大鼠分为:安静对照组、低氧即刻组、复氧1h组、复氧2h组、复氧6h组和复氧12h组。低氧暴露10h(氧浓度13.6%)。采用HPLC检测大鼠趾长伸肌AMP、ATP含量,蛋白印迹法检测MHC蛋白表达以及LKB1、AMPK、TSC2、mTOR磷酸化。结果:低氧暴露后即刻,骨骼肌AMP含量、AMP/ATP比值和LKB1、AMPK和TSC2磷酸化显著升高(P<0.01),同时mTOR磷酸化显著减少(P<0.01),均于复氧后6h恢复。结论:(1)低氧可通过AMP/ATP比值和LKB1来激活AMPK,并可经AMPK/TSC2/mTOR通路下调mTOR活性,进而抑制蛋白合成。AMP/ATP比值可能通过LKB1来激活AMPK。(2)低氧可通过AMPK/TSC2/mTOR通路抑制骨骼肌蛋白合成。
关键词: 低氧 LKB1 AMP/ATP AMPK mTOR
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Effects of Acution Hypoxia on AMPK/TSC2/mTOR Signaling Pathway in Skeletal Muscle of Rats
Abstract:Objective: The present study focused on the mechanism of hypoxia regulating skeletal muscle protein synthesis, and investigated the changing characteristics of LKB1, AMP/ATP, AMPK and mTOR signals in skeletal muscle in a reoxygen period after acute hypoxia exposure. Methods: Male SD rats were employed in the present research and randomly divided into groups: normoxia sedentary group, hypoxia instant group, reoxygen 1h group, reoxygen 2h group, reoxygen 6h group and reoxygen 12h group. A hypoxia exposure mode is defined as hypoxia exposure for 10 hours in a hypoxia room from 10 p.m. at night to 8 a.m. (oxygen concentration 13.6%). AMP and ATP contents in extensor digitorum longus (EDL) of a rat were examined by HPLC analysis. The phosphorylation of LKB1 Ser428, AMPK Thr172, TSC2 Thr1462 and mTOR Ser2448 were examined by western blotting analysis. Results: Immediately after hypoxia exposure, AMP content, AMP/ATP ratio and the phosphorylation of LKB1, AMPK and TSC2 in skeletal muscle increase remarkably (P<0.01), and meanwhile the phosphorylation of mTOR decreases remarkably (P<0.01), all of which restore to a sedentary level after reoxygen for 6h. Conclusions: (1) Hypoxia can activate AMPK via AMP/ATP ratio and LKB1 ways, and reduce the activity of mTOR via AMPK/TSC2/mTOR pathways, and further inhibit protein synthesis. AMP/ATP ratio possibly activates AMPK via LKB1. (2) Hypoxia inhibits protein synthesis in skeletal muscle via AMPK/TSC2/mTOR pathways.
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急性低氧对大鼠骨骼肌AMPK/TSC2/mTOR信号的影响
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