Restoration of Protein Synthesis in Heart and Skeletal Muscle after Withdrawal of Alcohol

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 [³H]-L-phenylalanine. The formation of active eukaryotic initiation factor (eIF)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.