Mammalian target of rapamycin pathway is up-regulated by both acute endurance exercise and chronic muscle contraction in rat skeletal muscle
Mammalian target of rapamycin pathway is up-regulated by both acute endurance exercise and chronic muscle contraction in rat skeletal muscle
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DOI：
10.1139/apnm-2012-0405
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发表时间：
2013-08-01
期刊：
影响因子：
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通讯作者：
Gurd, Brendon J.
中科院分区：
文献类型：
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作者：
Edgett, Brittany A.;Fortner, Melanie L.;Gurd, Brendon J.
本研究检测了急性耐力运动和慢性肌肉收缩活动后翻译起始调节蛋白和mRNA表达的变化。雌性Sprague道利大鼠在15 m处跑2 h。min（-1），然后每5 min增加5 μ min-1的速度，直到意志疲劳。从未运动的动物（对照; n = 6）和运动后立即运动的动物（n = 6）或从运动恢复3小时后运动的动物（n = 6）中收获红色腓肠肌。与对照组相比，核糖体蛋白S6（rpS 6）mRNA在0 h（+32%）和3 h（+47%）均升高（p < 0.05）。与对照组相比，真核细胞起始因子2B的催化亚基（eIF 2B β）（+127%）和雷帕霉素靶蛋白（mTOR）mRNA（+44%）在3 h时均增加。运动后即刻，mTOR（+40%）和S6激酶1（S6 K1）（+266%）的磷酸化增加（p < 0.05）。雌性Sprague道利大鼠也连续7天接受腓神经的慢性刺激。停止刺激后24 h，移除红色腓肠肌。慢性肌肉刺激增加（p < 0.05）mTOR蛋白（+74%）、rpS 6（+31%）和真核起始因子2 α（+44%，p = 0.069），并伴有细胞色素c（+31%）的增加。观察到rpS 6（+51%）（p < 0.05）的静息磷酸化增加，但未观察到mTOR或真核起始因子4 E结合蛋白1。这些实验表明，急性和慢性收缩活动上调小鼠骨骼肌中的mTOR途径和线粒体含量。这种mTOR途径的上调可能会增加翻译效率，也可能是运动介导的线粒体生物发生的重要控制点。
This study examined changes in the expression of translation initiation regulatory proteins and mRNA following both an acute bout of endurance exercise and chronic muscle contractile activity. Female Sprague Dawley rats ran for 2 h at 15 m . min(-1) followed by an increase in speed of 5 m u min-1 every 5 min until volitional fatigue. The red gastrocnemius muscle was harvested from nonexercised animals (control; n = 6) and from animals that exercised either immediately after exercise (n = 6) or following 3 h of recovery from exercise (n = 6). Compared with control, ribosomal protein S6 (rpS6) mRNA was elevated (p < 0.05) at both 0 h (+32%) and 3 h (+47%). Both a catalytic subunit of eukaryotic initiation factor 2B (eIF2B epsilon) (+127%) and mammalian target of rapamycin (mTOR) mRNA (+44%) were increased at 3 h, compared with control. Phosphorylation of mTOR (+40%) and S6 kinase 1 (S6K1) (+266%) were increased immediately after exercise (p < 0.05). Female Sprague Dawley rats also underwent chronic stimulation of the peroneal nerve continuously for 7 days. The red gastrocnemius muscle was removed 24 h after cessation of the stimulation. Chronic muscle stimulation increased (p < 0.05) mTOR protein (+74%), rpS6 (+31%), and eukaryotic initiation factor 2 alpha (+44%, p = 0.069), and this was accompanied by an increase in cytochrome c (+31%). Increased resting phosphorylation was observed for rpS6 (+51%) (p < 0.05) but not for mTOR or eukaryotic initiation factor 4E binding protein 1. These experiments demonstrate that both acute and chronic contractile activity up-regulate the mTOR pathway and mitochondrial content in murine skeletal muscle. This up-regulation of the mTOR pathway may increase translation efficiency and may also represent an important control point in exercise-mediated mitochondrial biogenesis.