Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signaling

American Journal of Physiology. Heart and Circulatory Physiology
Thomas C VaryStacy A Goodman

Abstract

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 intoxication alters the phosphorylation state of eukaryotic initiation factor (eIF) 4G, eIF4G.eIF4E complex formation, and the mammalian target of rapamycin (mTOR) signaling pathway in the heart. Acute alcohol intoxication was induced by injection of alcohol (75 mmol/kg body wt ip). Control animals received an equal volume of saline. Alcohol administration enhanced phosphorylation of eIF4G (Ser(1108)) approximately threefold. Alcohol administration lowered formation of the active eIF4G.eIF4E complex by >90%, whereas it increased the abundance of the inactive 4E-binding protein 1 (4E-BP1).eIF4E complex by approximately 160%. Phosphorylation of mTOR on Ser(2448) and Ser(2481) was decreased by 50%. Reduced mTOR phosphorylation did not result from decreased phosphorylation of PKB. Phosphorylation of 4E-BP1 and S6 kinase 1 (Thr(389)), downstream targets of mTOR, were also reduced after acute alcohol administration. These...Continue Reading

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Citations

Apr 11, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Thomas C VaryCharles H Lang
Dec 9, 2014·Autophagy·Jia Luo
Apr 21, 2017·Alcoholism, Clinical and Experimental Research·Jennifer L Steiner, Charles H Lang
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Sep 10, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Thomas C Vary
Nov 3, 2005·American Journal of Physiology. Endocrinology and Metabolism·Thomas C Vary, Christopher J Lynch
Apr 28, 2006·American Journal of Physiology. Endocrinology and Metabolism·Christopher J LynchThomas C Vary
Sep 2, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Thomas C VaryAndrew Sumner
Mar 29, 2007·American Journal of Physiology. Endocrinology and Metabolism·Thomas C VaryChristopher J Lynch

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