PMID- 15388509
OWN - NLM
STAT- MEDLINE
DCOM- 20050322
LR  - 20211203
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 288
IP  - 1
DP  - 2005 Jan
TI  - Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite 
      reducing mTOR signaling.
PG  - H121-8
AB  - 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 data suggest that acute alcohol-induced impairments 
      in myocardial mRNA translation initiation result, in part, from marked decreases 
      in eIF4G.eIF4E complex formation, which appear to be independent of changes in 
      phosphorylation of eIF4G but dependent on mTOR.
FAU - Vary, Thomas C
AU  - Vary TC
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, H166, 500 Univ. Dr., Hershey, PA 17033, USA. 
      tvary@psu.edu
FAU - Deiter, Gina
AU  - Deiter G
FAU - Goodman, Stacy A
AU  - Goodman SA
LA  - eng
GR  - AA-12814/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040923
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Ethanol/*poisoning
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Eukaryotic Initiation Factor-4G/*metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Myocardium/*metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases
EDAT- 2004/09/25 05:00
MHDA- 2005/03/23 09:00
CRDT- 2004/09/25 05:00
PHST- 2004/09/25 05:00 [pubmed]
PHST- 2005/03/23 09:00 [medline]
PHST- 2004/09/25 05:00 [entrez]
AID - 00440.2004 [pii]
AID - 10.1152/ajpheart.00440.2004 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H121-8. doi: 
      10.1152/ajpheart.00440.2004. Epub 2004 Sep 23.