Effects of chronic alcohol consumption on regulation of myocardial protein synthesis.
Heart disease represents an important etiology of mortality in chronic alcoholics. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of chronic alcohol exposure (16 wk) on the regulation of myocardial protein metabolism. Chronic alcohol feeding resulted in a lower heart weight and 25% loss of cardiac protein per heart compared with pair-fed controls. The loss of protein mass resulted in part from a diminished (30%) rate of protein synthesis. Ethanol exerted its inhibition of protein synthesis through diminished translational efficiency rather than lower RNA content. Chronic ethanol administration decreased the abundance of eukaryotic initiation factor (eIF)4G associated with eIF4E in the myocardium by 36% and increased the abundance of the translation response protein (4E-BP1) associated with eIF4E. In addition, chronic alcohol feeding significantly reduced the extent of p70S6 kinase (p70(S6K)) phosphorylation. The decreases in the phosphorylation of 4E-BP1 and p70(S6K) did not result from a reduced abundance of mammalian target of rapamycin (mTOR). These data suggest that a chronic alcohol-induced impairment in myocardial protein synthesis results in part from inhibition in peptide chain initiation secondary to marked changes in eIF4E availability and p70(S6K) phosphorylation.
Vary
T C
TC
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. tvary@psu.edu
Lynch
C J
CJ
Lang
C H
CH
D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003401:Creatine / Q000032:analysis; D002149:Energy Intake / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D039561:Eukaryotic Initiation Factor-4E; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010448:Peptide Initiation Factors / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D016276:Ventricular Function
D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D010725:Phosphocreatine; D000431:Ethanol; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019893:Ribosomal Protein S6 Kinases; D003401:Creatine