Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver

Charles H. Lang, Robert A. Frost, Vinayshree Kumar, Duanqing Wu, Thomas C. Vary

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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 [3H]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 eIF2α 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 eIF2α 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 γ-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.

Original languageEnglish (US)
Pages (from-to)322-331
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number3
DOIs
StatePublished - Mar 2000

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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