Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle
Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle
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DOI：
10.1113/jphysiol.2003.047019
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发表时间：
2003-11-15
影响因子：
5.5
通讯作者：
Jefferson, LS
中科院分区：
文献类型：
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作者：
Bolster, DR;Kubica, N;Jefferson, LS
本研究的目的是确定是否哺乳动物雷帕霉素靶蛋白（mTOR）介导的信号转导和翻译起始的一些关键调控蛋白在骨骼肌急性阻力运动后恢复的即时阶段发生改变。操作性地使大鼠适应到达位于有机玻璃笼高处的照明杆，使得动物完成涉及后肢肌肉组织的同心和离心收缩。急性运动后即刻及恢复后5、10、15、30、60 min分别取腓肠肌。Ser-473上的蛋白激酶B（PK B）的磷酸化在恢复10分钟时达到峰值（对照的282%，P < 0.05），而未注意到Ser-2448上的mTOR磷酸化的显著变化。真核起始因子（eIF）4 E-结合蛋白-1（4 E-BP 1）和S6激酶-1（SW 1），两者都是mTOR的下游效应子，在恢复过程中也发生了变化。4 E-BP 1磷酸化水平在恢复10 min时显著升高（292%，P < 0.01）。Thr-389上的S6 K1磷酸化在运动后10 min表现出峰值激活趋势（336%，P = 0.06），核糖体蛋白S6磷酸化在恢复15 min时最大激活（647%，P < 0.05）。在恢复过程中，eIF 4F复合物的组分增加，因为eIF 4 E与eIF 4G的结合在10 min时达到峰值（292%，P < 0.05）。通过eIF 2B活性和Ser-51上的eIF 2 α磷酸化来评估调节起始甲硫氨酰-tRNA与40 S核糖体亚基结合的事件。eIF 2B或eIF 2alpha均未观察到差异。总的来说，这些结果提供了强有力的证据表明，mTOR介导的信号传导是短暂的上调后的阻力运动的即时期间，这种反应可能构成最近的细胞生长反应。
The purpose of the present investigation was to determine whether mammalian target of rapamycin (mTOR)-mediated signalling and some key regulatory proteins of translation initiation are altered in skeletal muscle during the immediate phase of recovery following acute resistance exercise. Rats were operantly conditioned to reach an illuminated bar located high on a Plexiglass cage, such that the animals completed concentric and eccentric contractions involving the hindlimb musculature. Gastrocnemius muscle was extracted immediately after acute exercise and 5, 10, 15, 30 and 60 min of recovery. Phosphorylation of protein kinase B (PKB) on Ser-473 peaked at 10 min of recovery (282% of control, P < 0.05) with no significant changes noted for mTOR phosphorylation on Ser-2448. Eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) and S6 kinase-1 (SW1), both downstream effectors of mTOR, were altered during recovery as well. 4E-BP1 phosphorylation was significantly elevated at 10 min (292%, P < 0.01) of recovery. S6K1 phosphorylation on Thr-389 demonstrated a trend for peak activation at 10 min following exercise (336%, P = 0.06) with ribosomal protein S6 phosphorylation being maximally activated at 15 min of recovery (647%, P < 0.05). Components of the eIF4F complex were enhanced during recovery as eIF4E association with eIF4G peaked at 10 min (292%, P < 0.05). Events regulating the binding of initiator methionyl-tRNA to the 40S ribosomal subunit were assessed through eIF2B activity and eIF2alpha phosphorylation on Ser-51. No differences were noted with either eIF2B or eIF2alpha. Collectively, these results provide strong evidence that mTOR-mediating signalling is transiently upregulated during the immediate period following resistance exercise and this response may constitute the most proximal growth response of the cell.