Impaired myocardial protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4F

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

Research output: Contribution to journalArticle

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Abstract

The purpose of the present study was to examine potential mechanisms for the known inhibitory effect of acute alcohol exposure on myocardial protein synthesis. Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and protein synthesis was measured in vivo 2.5 h thereafter by use of the flooding-dose L-[3H]phenylalanine technique. Rates of myocardial protein synthesis and translational efficiency in alcohol-treated rats were decreased compared with control values. Free (nonpolysome bound) 40S and 60S ribosomal subunits were increased 50% after alcohol treatment, indicating an impaired peptide-chain initiation. To identify mechanisms responsible for this impairment, several eukaryotic initiation factors (eIF) were analyzed. Acute alcohol intoxication did not significantly alter the myocardial content of eIF2α or eIF2Bε, the extent of eIF2α phosphorylation, or the activity of eIF2B. Acute alcohol exposure increased the binding of 4E-binding protein 1 (4E-BP1) to eIF4E (55%), diminished the amount of eIF4E bound to eIF4G (70%), reduced the amount of 4E-BP1 in the phosphorylated γ-form (40%), and decreased the phosphorylation of p70S6 kinase and the ribosomal protein S6. There was no significant difference in either the plasma insulin-like growth factor (IGF) I concentration (total or free) or expression of IGF-I or IGF-II mRNA in heart between the two groups. These data suggest that the acute alcohol-induced impairment in myocardial protein synthesis results, in part, from an inhibition in peptide-chain initiation, which is associated with marked changes in eIF4E availability and p70S6 kinase phosphorylation but is independent of changes in the eIF2/2B system and IGFs.

Original languageEnglish (US)
Pages (from-to)E1029-E1038
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume279
Issue number5 42-5
StatePublished - Dec 12 2000

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Alcoholic Intoxication
Alcohols
Phosphorylation
Proteins
Insulin-Like Growth Factor I
Carrier Proteins
Eukaryotic Large Ribosome Subunits
Eukaryotic Small Ribosome Subunits
Ribosomal Protein S6 Kinases
Eukaryotic Initiation Factors
Peptides
Insulin-Like Growth Factor II
Phenylalanine
Ethanol
Phosphotransferases
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

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abstract = "The purpose of the present study was to examine potential mechanisms for the known inhibitory effect of acute alcohol exposure on myocardial protein synthesis. Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and protein synthesis was measured in vivo 2.5 h thereafter by use of the flooding-dose L-[3H]phenylalanine technique. Rates of myocardial protein synthesis and translational efficiency in alcohol-treated rats were decreased compared with control values. Free (nonpolysome bound) 40S and 60S ribosomal subunits were increased 50{\%} after alcohol treatment, indicating an impaired peptide-chain initiation. To identify mechanisms responsible for this impairment, several eukaryotic initiation factors (eIF) were analyzed. Acute alcohol intoxication did not significantly alter the myocardial content of eIF2α or eIF2Bε, the extent of eIF2α phosphorylation, or the activity of eIF2B. Acute alcohol exposure increased the binding of 4E-binding protein 1 (4E-BP1) to eIF4E (55{\%}), diminished the amount of eIF4E bound to eIF4G (70{\%}), reduced the amount of 4E-BP1 in the phosphorylated γ-form (40{\%}), and decreased the phosphorylation of p70S6 kinase and the ribosomal protein S6. There was no significant difference in either the plasma insulin-like growth factor (IGF) I concentration (total or free) or expression of IGF-I or IGF-II mRNA in heart between the two groups. These data suggest that the acute alcohol-induced impairment in myocardial protein synthesis results, in part, from an inhibition in peptide-chain initiation, which is associated with marked changes in eIF4E availability and p70S6 kinase phosphorylation but is independent of changes in the eIF2/2B system and IGFs.",
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Impaired myocardial protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4F. / Lang, Charles H.; Frost, Robert A.; Kumar, Vinayshree; Vary, Thomas C.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 279, No. 5 42-5, 12.12.2000, p. E1029-E1038.

Research output: Contribution to journalArticle

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