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：
10.1111/j.1530-0277.2000.tb04614.x
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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：大鼠急性酒精中毒可降低骨骼肌蛋白质合成，并在较小程度上降低肝脏蛋白质合成。本研究的目的是研究潜在的机制，急性乙醇exposure.Methods的抑制作用：大鼠腹腔注射乙醇（75 mmol/kg）或生理盐水，和组织进行了检查2.5小时后。在体内的蛋白质合成率测定[H-3]苯丙氨酸掺入到蛋白质中，和各种真核起始因子（eIFs）进行定量Western印迹分析，以确定可能的机制，调节translation.Results：蛋白质合成腓肠肌和肝脏减少（39%和21%，分别）酒精管理后，与盐水注射对照动物。酒精管理没有改变组织RNA含量，但降低了肌肉（43%）和肝脏（24%）的翻译效率。在酒精处理的大鼠中，肝脏eIF 2B活性降低24%，这与eIF 2 α磷酸化增加95%有关。然而，酒精不会改变与eIF 4 E结合的4 E结合蛋白1（4 E-BP 1）、与eIF 4G结合的eIF 4 E的量，也不会改变4 E-BP 1或eIF 4 E的磷酸化状态。与肝脏相反，酒精处理的大鼠肌肉中eIF 2B活性和eIF 2 α磷酸化均未受到影响。然而，急性酒精中毒增加了4 E-BP 1与eIF 4 E的结合（113%），减少了与eIF 4G结合的eIF 4 E的量（81%），并减少了磷酸化γ形式的4 E-BP 1的量（77%）。结论：急性酒精中毒可通过不同的机制降低肝脏和肌肉中胰岛素和胰岛素样生长因子-I信使核糖核酸的含量。eIF 2B的变化似乎在肝脏中占主导地位，而eIF 4 E可用性的改变似乎在骨骼肌中对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.