Restoration of protein synthesis in heart and skeletal muscle after withdrawal of alcohol
Restoration of protein synthesis in heart and skeletal muscle after withdrawal of alcohol
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DOI：
10.1097/01.alc.0000121653.80502.54
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发表时间：
2004-04-01
影响因子：
3.2
通讯作者：
Lang, CH
中科院分区：
文献类型：
--
作者：
Vary, TC;Nairn, AC;Lang, CH
背景：长期饮酒后，由于 mRNA 翻译起始和延伸的变化，蛋白质合成速率降低。目前尚不清楚戒除乙醇后酒精对蛋白质合成的不利影响会持续多久。 方法：我们研究了慢性酒精暴露（16 周）后 72 小时从大鼠饮食中去除酒精对蛋白质合成速率的影响以及控制心脏、骨骼肌和肝脏中 mRNA 翻译的潜在机制。静脉输注[H-3]-L-苯丙氨酸后测量蛋白质合成率。测量每个组织中活性真核起始因子 (elF)4E(.)eIF4G 复合物的形成、真核延伸因子 (eEF)1A 和 eEF2 的细胞含量以及 eEF2 和 S6K1 的磷酸化状态。 结果：从饮食中戒除酒精后，心脏和骨骼肌中的蛋白质合成恢复到未接触酒精的配对喂养对照大鼠中获得的值。然而，器官重量和每块肌肉的蛋白质含量不受饮食中酒精戒断的影响。在心脏和骨骼肌中，蛋白质合成的恢复与活性 eIF4E(.)eIF4G 复合物和 eEF1A 含量形成缺陷的逆转相关。从饮食中戒除酒精后，心肌 eEF2 含量也恢复至对照值。在腓肠肌中，eEF2 的细胞含量减少。较低的 eIF2 含量可能通过 eEF2 磷酸化状态的降低而增加的 eEF2 活性所抵消，从而使蛋白质合成不受阻碍地进行。结论：这些研究表明，长期饮酒期间观察到的蛋白质代谢变化是可逆的，在现阶段并不代表心肌或骨骼肌发生不可逆的变化。
Background: The rate of protein synthesis is diminished after chronic alcohol consumption through changes in both mRNA translation initiation and elongation. It remains unknown how long adverse effects of alcohol on protein synthesis persist after withdrawal from ethanol.Methods: We examined the effect of removal of alcohol from the diet of rats for 72 hr after chronic alcohol exposure (16 weeks) on rates of protein synthesis and potential mechanisms for controlling mRNA translation in heart, skeletal muscle, and liver. Rates of protein synthesis were measured after intravenous infusion of [H-3]-L-phenylalanine. The formation of active eukaryotic initiation factor (elF)4E(.)eIF4G complex, the cellular content of eukaryotic elongation factor (eEF)1A and eEF2, and the phosphorylation state of eEF2 and S6K1 were measured in each tissue.Results: Withdrawal of alcohol from the diet restored protein synthesis in heart and skeletal muscle to values obtained in pair-fed control rats not exposed to alcohol. However, the organ weight and protein content per muscle was not affected by withdrawal of alcohol from the diet. In both heart and skeletal muscle, the restoration of protein synthesis correlated with reversal of defects in the formation of active eIF4E(.)eIF4G complex and eEF1A content. Myocardial eEF2 content was also restored to control values after withdrawal of alcohol from the diet. In the gastrocnemius, there was a decrease in the cellular content of eEF2. The lower eIF2 content may have been counterbalanced by an increased activity of eEF2 through a reduction in the phosphorylation state of eEF2 allowing protein synthesis to proceed unimpeded.Conclusions: These studies indicate that changes in protein metabolism observed during chronic alcohol intake are reversible and do not, at this stage, represent an irreversible change in cardiac or skeletal muscle.