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* To whom correspondence should be addressed. E-mail: tvary{at}psu.edu.
Acute alcohol intoxication impairs myocardial protein synthesis in rats secondary to a diminished mRNA translational efficiency. Decreased mRNA translational efficiency occurs through altered regulation of peptide-chain initiation. The purpose of the present set of experiments was to determine whether acute alcohol (EtOH) intoxication alters the phosphorylation state of eIF4G, eIF4G.eIF4E complex formation and the mammalian target of rapamycin (mTOR) signaling pathway in heart. Acute alcohol intoxication was induced by intraperitoneal injection of EtOH (75 mmol/kg body wt). Control animals received an equal volume of saline. EtOH administration enhanced phosphorylation of eIF4G (Ser1108) approximately 3-fold. EtOH administration lowered the formation of active eIF4G.eIF4E complex by over 90% whereas it increased the abundance of the inactive 4E-BP1.eIF4E complex by ~160%. Phosphorylation of mTOR on Ser2448 and Ser2481 was decreased by 50%. Reduced mTOR phosphorylation did not result from a decreased phosphorylation of PKB. Phosphorylation of both 4E-BP1 and S6K1(Thr389), downstream targets of mTOR, were also reduced following acute alcohol injection. These data suggest that acute alcohol-induced impairments in myocardial mRNA translation initiation results, in part, from marked decreases in eIF4E.eIF4G complex formation that appear independent of changes in the phosphorylation of eIF4G but dependent upon mTOR.
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