Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver
Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver
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DOI：
10.1097/00000374-200003000-00010
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发表时间：
2000-03-01
影响因子：
3.2
通讯作者：
Vary, TC
中科院分区：
文献类型：
--
作者：
Lang, CH;Frost, RA;Vary, TC
背景：大鼠急性酒精中毒会降低骨骼肌中的蛋白质合成，并在较小程度上降低肝脏中的蛋白质合成。本研究的目的是检查急性乙醇暴露抑制作用的潜在机制。方法：给大鼠腹腔注射乙醇（75 mmol/kg）或盐水，2.5小时后检查组织。通过 [H-3] 苯丙氨酸掺入蛋白质来测定体内蛋白质合成率，并通过蛋白质印迹分析对各种真核起始因子 (eIF) 进行定量，以确定调节翻译的可能机制。 结果：与注射盐水的对照动物相比，饮酒后腓肠肌和肝脏中的蛋白质合成减少（分别为 39% 和 21%）。饮酒不会改变组织 RNA 含量，但会降低肌肉 (43%) 和肝脏 (24%) 的翻译效率。在酒精处理的大鼠中，肝脏 eIF2B 活性降低了 24%，这与 eIF2 α 磷酸化增加 95% 相关。然而，酒精不会改变与 eIF4E 结合的 4E 结合蛋白 1 (4E-BP1) 的量、与 eIF4G 结合的 eIF4E 的量，或者 4E-BP1 或 eIF4E 的磷酸化状态。与肝脏相反，酒精治疗大鼠肌肉中的 eIF2B 活性和 eIF2 α 磷酸化均未受到影响。然而，急性酒精中毒增加了 4E-BP1 与 eIF4E 的结合（113%），减少了 eIF4E 与 eIF4G 结合的量（81%），并减少了磷酸化 γ 形式的 4E-BP1 的量（77%）。酒精不会改变胰岛素和胰岛素样生长因子-I 的血浆浓度，但肌肉胰岛素样生长因子-I 信使核糖核酸丰度降低 35%。 结论：这些数据表明，急性酒精中毒通过不同机制减少肝脏和肌肉中的翻译起始和蛋白质合成。 eIF2B 的变化似乎在肝脏中占主导地位，而 eIF4E 可用性的变化似乎在骨骼肌中对于控制翻译起始更为关键。
Background: Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure.Methods: Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and tissues were examined 2.5 hr later. Rates of protein synthesis in vivo were determined by [H-3]phenylalanine incorporation into protein, and various eukaryotic initiation factors (eIFs) were quantitated by Western blot analysis to identify possible mechanisms for regulating translation.Results: Protein synthesis in gastrocnemius and liver was decreased (39% and 21%, respectively) after alcohol administration, compared with saline-injected control animals. Alcohol administration did not alter tissue RNA content but diminished translational efficiency in muscle (43%) and liver (24%). Hepatic eIF2B activity was decreased 24% in alcohol-treated rats, and this was associated with a 95% increase in eIF2 alpha phosphorylation. However, alcohol did not alter the amount of 4E-binding protein 1 (4E-BP1) bound to eIF4E, eIF4E bound to eIF4G, or the phosphorylation state of either 4E-BP1 or eIF4E. In contrast to liver, neither eIF2B activity nor the phosphorylation of eIF2 alpha was affected in muscle of alcohol-treated rats. However, acute alcohol intoxication increased binding of 4E-BP1 to eIF4E (113%), decreased the amount of eIF4E bound to eIF4G (81%), and decreased the amount of 4E-BP1 in the phosphorylated gamma-form (77%). The plasma concentrations of insulin and insulin-like growth factor-I were unchanged by alcohol, but muscle insulin-like growth factor-I messenger ribonucleic acid abundance was decreased 35%.Conclusions: These data suggest that acute alcohol intoxication decreases translation initiation and protein synthesis in liver and muscle via different mechanisms. Changes in eIF2B appear to predominate in liver, whereas alterations in eIF4E availability appear more critical in skeletal muscle for controlling translation initiation.