Alcohol myopathy: impairment of protein synthesis and translation initiation.
Alcohol consumption leads to numerous morphological, biochemical and functional changes in skeletal and cardiac muscle. One such change observed in both tissues after either acute alcohol intoxication or chronic alcohol consumption is a characteristic decrease in the rate of protein synthesis. A decrease in translation efficiency appears to be responsible for at least part of the reduction. This review highlights advances in determining the molecular mechanisms by which alcohol impairs protein synthesis and places these observations in context of earlier studies on alcoholic myopathy. Both acute and chronic alcohol administration impairs translational control by modulating various aspects of peptide-chain initiation. Moreover, this alcohol-induced impairment in initiation is associated with a decreased availability of eukaryotic initiation factor (eIF) 4E in striated muscle, as evidenced by an increase in the amount of the inactive eIF4E.4E-BP1 complex and decrease in the active eIF4E.eIF4G complex. In contrast, alcohol does not produce consistent alterations in the control of translation initiation by the eIF2 system. The etiology of these changes remain unresolved. However, defects in the availability or effectiveness of various anabolic hormones, particularly insulin-like growth factor-I, are consistent with the alcohol-induced decrease in protein synthesis and translation initiation.
Lang
C H
CH
Department of Cellular and Molecular Physiology (H166), Penn State College of Medicine, Hershey, PA 17033, USA. clang@psu.edu
Kimball
S R
SR
Frost
R A
RA
Vary
T C
TC
D000818:Animals; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity*; D039561:Eukaryotic Initiation Factor-4E; D005260:Female; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism
D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D011506:Proteins; D013002:Somatomedins; D000431:Ethanol; D013006:Growth Hormone