Regulation of REDD1 by Insulin-Like Growth Factor-I in Skeletal Muscle and Myotubes
Regulation of REDD1 by Insulin-Like Growth Factor-I in Skeletal Muscle and Myotubes
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DOI：
10.1002/jcb.22349
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Lang, Charles H.
中科院分区：
文献类型：
--
作者：
Frost, Robert A.;Huber, Danuta;Lang, Charles H.
胰岛素样生长因子- i （IGF-I）是骨骼肌的主要合成代谢激素，是蛋白质合成和翻译起始的有效刺激。最近的研究表明，过表达雷帕霉素靶蛋白（mTOR）阻遏物redd1可以抑制翻译。本研究的目的是确定IGF-I是否会改变redd1的表达，以及这是否与体外蛋白质合成的伴随变化有关。皮下注射igf -1或静脉注射胰岛素3-4h，骨骼肌中redd1 mRNA增加7-10倍。当C2C12肌管中加入IGF-I后，redd1蛋白在24小时内持续表达时，redd1蛋白增加了三倍。从肌管中撤出igf - 1会导致redd1蛋白含量的快速损失。igf -i诱导的redd1 mRNA和蛋白表达被转录和翻译抑制剂阻断。igf - 1与地塞米松（Dex）对肌管中redd1蛋白含量有累加作用。PI3K抑制剂LY294002阻断igf - 1，但不阻断Dex诱导的redd1。igf - 1也刺激redd1启动子活性。虽然在肌管中添加igf - 1后，REDD1蛋白升高了5-6个单位，但在这个I - h窗口期间测量的蛋白合成在表达更多REDD1的肌管中反而更高。与IGF-I诱导的REDD 1 mRNA的增加相反，IGF-I导致REDD2 mRNA的减少。我们得出结论，IGF-I刺激骨骼肌和肌管中REDD 1的表达，但在这些条件下，REDD 1的反应不足以抑制蛋白质合成。j .细胞。中国生物医学工程学报，2009,31(2):391 - 391。(C) 2009 Wiley-Liss, Inc。
Insulin-like growth factor-I (IGF-I) is a major anabolic hormone for skeletal muscle and a potent stimulus for protein synthesis and translation initiation. Recent studies suggest that translation can be inhibited by over expression of the mammalian target of rapamycin (mTOR) repressor REDD 1. The purpose of the present study was to determine whether IGF-I alters the expression of REDD 1 and whether this is associated with a concomitant change in protein synthesis in vitro. Subcutaneous injection of IGF-I or intravenous delivery of insulin for 3-4h increased REDD 1 mRNA in skeletal muscle 7-10-fold. A threefold increase in REDD 1 was observed when C2C12 myotubes were treated with IGF-I-REDD 1 protein continued to be expressed for up to 24 h after addition of IGF-I to cells. Withdrawal of IGF-I from myotubes lead to a rapid loss of REDD 1 protein content. IGF-I-induced REDD 1 mRNA and protein expression were prevented by inhibitors of transcription and translation. IGF-I had an additive effect with dexamethasone (Dex) on REDD 1 protein content in myotubes. The PI3K inhibitor LY294002 blocked IGF-I but not Dex induced REDD 1. IGF-I also stimulated REDD 1 promoter activity. Although REDD1 protein was elevated 5-6 It after addition of IGF-I to myotubes, protein synthesis measured during this I h window was paradoxically greater in myotubes expressing more REDD 1. In contrast to the IGF-I induced increase in REDD 1 mRNA, REDD2 mRNA was decreased by IGF-I We conclude that IGF-I stimulates REDD 1 expression in skeletal muscle and myotubes but under these conditions the REDD 1 response is not sufficient to repress protein synthesis. J. Cell. Biochem. 108: 1192-1202, 2009. (C) 2009 Wiley-Liss, Inc.