Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids
Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids
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DOI：
10.1016/j.bbrc.2003.07.014
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发表时间：
2004-01-09
影响因子：
3.1
通讯作者：
Jefferson, LS
中科院分区：
文献类型：
--
作者：
Kimball, SR;Jefferson, LS
支链氨基酸作为骨骼肌中蛋白质合成的营养调节剂的重要性在20多年前就被认识到。在支链氨基酸中，亮氨酸尤其被证明在促进肌肉蛋白质合成中发挥核心作用。然而，直到最近才开始确定亮氨酸刺激蛋白质合成的机制。在我们的实验室在过去几年中进行的研究表明，口服亮氨酸禁食大鼠增强蛋白质合成与增加磷酸化的蛋白激酶下游的两种蛋白质称为哺乳动物雷帕霉素靶（mTOR）。这些蛋白质，真核起始因子eIF 4 E结合蛋白（4 E-BP）1和核糖体蛋白S6激酶S6 K1，部分控制翻译起始步骤，包括mRNA与40 S核糖体亚基的结合。理论上，所有mRNA的翻译都可以通过这种机制进行调节，然而，一些mRNA对这些变化比其他mRNA更敏感，从而通过改变特定mRNA的翻译模式来调节基因表达。此外，尽管亮氨酸需要基础量的血浆胰岛素来增强mTOR下游的信号传导，但在禁食大鼠的血浆中观察到的浓度足以观察到4 E-BP 1和S6 K1磷酸化的最大变化。(C)2003年爱思唯尔公司All rights reserved.
The importance of branched-chain amino acids as nutrient regulators of protein synthesis in skeletal muscle was recognized more than 20 years ago. Of the branched-chain amino acids, leucine in particular was shown to play a central role in promoting muscle protein synthesis. However, it was only recently that the mechanism(s) involved in the stimulation of protein synthesis by leucine has begun to be defined. Studies performed in our laboratory during the past few years have revealed that oral administration of leucine to fasted rats enhances protein synthesis in association with increased phosphorylation of two proteins downstream of the protein kinase referred to as the mammalian target of rapamycin (mTOR). These proteins, eukaryotic initiation factor eIF4E binding protein (4E-BP)1 and ribosomal protein S6 kinase S6K1, control in part the step in translation initiation involving the binding of mRNA to the 40S ribosomal subunit. In theory the translation of all mRNAs can be regulated through such mechanisms, however, some mRNAs are more sensitive to the changes than others, resulting in modulation of gene expression through altered patterns of translation of specific mRNAs. Moreover, although a basal amount of plasma insulin is required for leucine to enhance signaling downstream of mTOR, the concentration observed in plasma of fasted rats is sufficient to observe maximal changes in phosphorylation of 4E-BP1 and S6K1. (C) 2003 Elsevier Inc. All rights reserved.