Vary T C, Jefferson L S, Kimball S R
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E58-64. doi: 10.1152/ajpendo.2000.278.1.E58.
Insulin-like growth factor I (IGF-I) promotes anabolism by stimulating protein synthesis in skeletal muscle. In the present study, we have examined mechanisms by which IGF-I stimulates protein synthesis in skeletal muscle with a perfused rat hindlimb preparation. IGF-I (10 nM) stimulated protein synthesis over 2.7-fold. Total RNA content was unaffected, but translational efficiency was increased by IGF-I. We next examined the effect of IGF-I on eukaryotic initiation factor (eIF) 4E as a mechanism regulating translation initiation. IGF-I did not alter either the amount of eIF4E associated with the eIF4E binding protein 4E-BP1 or the phosphorylation state of 4E-BP1. Likewise, the phosphorylation state of eIF4E was unaltered by IGF-I. In contrast, the amount of eIF4E bound to eIF4G was increased threefold by IGF-I. We conclude that IGF-I regulates protein synthesis in skeletal muscle by enhancing formation of the active eIF4E x eIF4G complex.
胰岛素样生长因子I（IGF-I）通过刺激骨骼肌中的蛋白质合成来促进合成代谢。在本研究中，我们利用灌注大鼠后肢制备模型研究了IGF-I刺激骨骼肌蛋白质合成的机制。IGF-I（10 nM）使蛋白质合成增加了2.7倍以上。总RNA含量未受影响，但IGF-I提高了翻译效率。接下来，我们研究了IGF-I对真核起始因子（eIF）4E的影响，将其作为调节翻译起始的一种机制。IGF-I既未改变与eIF4E结合蛋白4E-BP1结合的eIF4E的量，也未改变4E-BP1的磷酸化状态。同样，IGF-I也未改变eIF4E的磷酸化状态。相反，IGF-I使与eIF4G结合的eIF4E的量增加了三倍。我们得出结论，IGF-I通过增强活性eIF4E×eIF4G复合物的形成来调节骨骼肌中的蛋白质合成。
