Time Course Change of IGF1/Akt/mTOR/p70s6k Pathway Activation in Rat Gastrocnemius Muscle During Repeated Bouts of Eccentric Exercise.
Time Course Change of IGF1/Akt/mTOR/p70s6k Pathway Activation in Rat Gastrocnemius Muscle During Repeated Bouts of Eccentric Exercise.
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发表时间：
2010-06
影响因子：
3.2
通讯作者：
E. Ochi;N. Ishii;K. Nakazato
中科院分区：
文献类型：
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作者：
E. Ochi;N. Ishii;K. Nakazato
本研究旨在探讨慢性偏心运动是否会改变大鼠腓肠肌内侧肌胰岛素样生长因子（IGF-1）和Akt/mTOR/p70S6K通路活性。雄性Wistar大鼠24只，随机分为2组：偏心运动组（ECC）和假手术对照组（CON）。ECC组每2天训练1次，共10天（共5次）或20天（共10次）。在5或10次运动后，肌肉标本被解剖并称重。采用实时逆转录聚合酶链式反应（RT-PCR）检测IGF-1及其变体机械生长因子（MGF）的mRNA表达。western blot检测组织中Akt (P)、mTOR (P)、p70S6K (P)的浓度。运动5次后，ECC组腓肠肌内侧肌质量无显著差异，而运动10次后，肌肉质量显著增加，肌纤维横截面积增加（p < 0.05）。10次运动后大鼠IGF-1 mRNA的表达和Akt (P)、p70S6K (P)的组织浓度显著高于同龄对照组和5次运动组。MGF mRNA在ECC5S和ECC10S中的表达均显著高于各周期匹配对照组（p < 0.01）。与对照组比较，10个疗程后mTOR组织浓度(P)显著升高（P < 0.01）。这些结果表明，IGF-1/Akt/mTOR/p70S6K信号通路的激活在慢性运动后期成为主导，此时观察到明显的肌肉肥大。我们证实，使用原始开发的设备的大鼠肌肉运动模型在10次（20天）中增加了腓肠肌内侧肌的湿质量和肌纤维的横截面积，但在5次（10天）中没有增加。我们发现肌肉质量和肌纤维CSA的增加伴随着IGF-1 mRNA、磷酸化Akt、mTOR和p70S6K的表达。这些结果表明，在我们的模型中，肌肉肥大是在10次运动后实现的，并与IGF-1/Akt/mTOR/p70S6K信号通路的激活有关。
The purpose of this study was to examine whether insulin-like growth factor (IGF-1) and Akt/mTOR/p70S6K pathway activity is altered by chronic eccentric exercise in rat medial gastrocnemius muscle. Male Wistar rats (n = 24) were randomly assigned to 1 of the 2 groups: eccentric exercise (ECC) group or sham-operated control (CON) group. Rats in the ECC group were trained every second day for 10 days (5 sessions in total) or 20 days (10 sessions in total). After either 5 or 10 exercise sessions, muscle specimens were dissected and weighed. The mRNA expression of IGF-1 and its variant, mechano growth factor (MGF), was evaluated using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Tissue concentrations of Akt (P), mTOR (P), and p70S6K (P) were measured by using western blot analysis. The medial gastrocnemius muscle mass of the ECC group did not show any significant difference after 5 exercise sessions, whereas the muscle mass increased significantly after 10 exercise sessions with a concomitant increase in the cross-sectional area of muscle fibers (p < 0.05). The expression of IGF-1 mRNA and the tissue concentrations of Akt (P) and p70S6K (P) after 10 exercise sessions was significantly higher than those of the age-matched controls and the rats that received 5 exercise sessions. The expression of MGF mRNA in both ECC5S and ECC10S were significantly higher than that in each period-matched control (p < 0.01). The tissue concentration of mTOR (P) after 10 sessions showed a significant increase when compared with period-matched controls (p < 0.01). These results suggest that activation of the IGF-1/Akt/mTOR/p70S6K signaling pathway becomes dominant in the later phase of chronic exercise, when significant muscular hypertrophy is observed. Key pointsWe confirmed that the rat muscular exercise model using originally-developed equipment increased the wet mass of the medial gastrocnemius muscle and cross-sectional areas of muscle fibres in 10 sessions (20 days) but not in 5 sessions (10days).We clarified that the increases of muscle mass and CSA of muscle fibers were accompanied by IGF-1 mRNA expression, the phosphorylated Akt, mTOR, and p70S6K.These results suggest that muscular hypertrophy in our model was achieved after 10 sessions of exercise and associated with the activation of IGF-1/Akt/mTOR/p70S6K signal pathway.