Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle.
Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle.
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DOI：
10.1152/ajpendo.2000.278.1.e76
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
O. Shah;S. Kimball;L. Jefferson
中科院分区：
文献类型：
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作者：
O. Shah;S. Kimball;L. Jefferson
糖皮质激素是一种促糖尿病因子，它不仅能拮抗胰岛素在靶组织中的作用，还能使这些组织分解代谢。因此，在大鼠中，我们试图表征糖皮质激素在骨骼肌中对翻译起始的影响，这是一个受调控的过程，部分地通过真核起始因子(EIF)的调节活性来调控整体蛋白质合成。腹腔注射地塞米松(100微克/100g体重)4h后，骨骼肌蛋白质合成减少至对照组的59%。此外，翻译起始因子eIF4E更倾向于与其内源性抑制物4E-BP1结合，而不是eIF4G。地塞米松处理导致4E-BP1和40S核糖体蛋白S6激酶的去磷酸化，同时伴随着eIF4E的增强磷酸化。此外，eIF2B的鸟嘌呤核苷酸交换活性不受影响，eIF2α亚基的磷酸化也不受影响。因此，糖皮质激素负向调节蛋白质合成机制的一个子集的激活，从而促进这类激素在体内的分解代谢特性。
Glucocorticoids are diabetogenic factors that not only antagonize the action of insulin in target tissues but also render these tissues catabolic. Therefore, in rats, we endeavored to characterize the effects in skeletal muscle of glucocorticoids on translation initiation, a regulated process that, in part, governs overall protein synthesis through the modulated activities of eukaryotic initiation factors (eIFs). Four hours after intraperitoneal administration of dexamethasone (100 microg/100 g body wt), protein synthesis in skeletal muscle was reduced to 59% of the value recorded in untreated control animals. Furthermore, translation initiation factor eIF4E preferred association with its endogenous inhibitor 4E-BP1 rather than eIF4G. Dexamethasone treatment resulted in dephosphorylation of both 4E-BP1 and the 40S ribosomal protein S6 kinase concomitant with enhanced phosphorylation of eIF4E. Moreover, the guanine nucleotide exchange activity of eIF2B was unaffected as was phosphorylation of the alpha-subunit of eIF2. Hence glucocorticoids negatively modulate the activation of a subset of the protein synthetic machinery, thereby contributing to the catabolic properties of this class of hormones in vivo.