Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway.
Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway.
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DOI：
10.1093/jn/130.10.2413
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
J. Anthony;F. Yoshizawa;T. Anthony;T. Vary;L. Jefferson;S. Kimball
中科院分区：
文献类型：
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作者：
J. Anthony;F. Yoshizawa;T. Anthony;T. Vary;L. Jefferson;S. Kimball
本研究的目的有两个：1）确定亮氨酸是否是支链氨基酸（BCAA）中唯一的刺激食物剥夺大鼠骨骼肌蛋白质合成的能力; 2）研究亮氨酸给药后肌肉蛋白质合成的变化是否涉及包括蛋白激酶哺乳动物雷帕霉素靶蛋白（mTOR）的信号传导途径。在第一组实验中，对禁食（18小时）的雄性大鼠（200 g）口服生理盐水或270 mg缬氨酸、异亮氨酸或亮氨酸。在第二组实验中，在亮氨酸给药之前，给食物剥夺的大鼠静脉注射雷帕霉素（0.75 mg/kg），雷帕霉素是mTOR的特异性抑制剂。仅亮氨酸刺激骨骼肌蛋白质合成高于盐水处理对照（P：< 0.05）。此外，亮氨酸是最有效的支链氨基酸在增强磷酸化的真核生物起始因子（eIF），4 E结合蛋白1（4 E-BP 1）和70 kDa的核糖体蛋白S6激酶（S6 K1）。4 E-BP 1的亮氨酸依赖性过度磷酸化增加了eIF 4 E形成活性eIF4G.eIF4E复合物的可用性。在较小程度上，异亮氨酸也增强4 E-BP 1和S6 K1的磷酸化。雷帕霉素抑制蛋白质合成亮氨酸治疗和食物剥夺大鼠。此外，雷帕霉素阻止了亮氨酸对eIF 4 E结合eIF 4G的刺激作用，并抑制了S6 K1的亮氨酸依赖性磷酸化。这些数据表明，亮氨酸是独特的支链氨基酸中，其刺激蛋白质合成的能力，在肌肉中的食物剥夺大鼠。我们第一次表明，亮氨酸依赖的刺激翻译起始在体内发生通过雷帕霉素敏感的途径。
The objectives of the present study were twofold: 1) to determine whether leucine is unique among the branched-chain amino acids (BCAA) in its ability to stimulate protein synthesis in skeletal muscle of food-deprived rats; and 2) to investigate whether changes in muscle protein synthesis after leucine administration involve a signaling pathway that includes the protein kinase mammalian target of rapamycin (mTOR). In the first set of experiments, food-deprived (18 h) male rats (200 g) were orally administered saline or 270 mg valine, isoleucine or leucine. In the second set of experiments, food-deprived rats were injected intravenously with rapamycin (0.75 mg/kg), a specific inhibitor of mTOR, before leucine administration. Only leucine stimulated protein synthesis in skeletal muscle above saline-treated controls (P: < 0.05). Furthermore, leucine was most effective among the BCAA at enhancing phosphorylation of eukaryotic initiation factor (eIF), 4E binding protein 1 (4E-BP1) and the 70-kDa ribosomal protein S6 kinase (S6K1). Leucine-dependent hyperphosphorylation of 4E-BP1 increased the availability of eIF4E to form the active eIF4G.eIF4E complex. To a lesser extent, isoleucine also enhanced phosphorylation of 4E-BP1 and S6K1. Rapamycin inhibited protein synthesis in both leucine-treated and food-deprived rats. Additionally, rapamycin prevented the stimulatory effects of leucine on eIF4E availability for binding eIF4G and inhibited leucine-dependent phosphorylation of S6K1. The data demonstrate that leucine is unique among the BCAA in its ability to stimulate protein synthesis in muscle of food-deprived rats. We show for the first time that leucine-dependent stimulation of translation initiation in vivo occurs via a rapamycin-sensitive pathway.