title: Alcohol impairs protein synthesis and degradation in cultured skeletal muscle cells.
abstract: BACKGROUND
  Acute and chronic alcohol intoxication decreases skeletal muscle protein synthesis under in vivo conditions. We investigated whether ethanol (EtOH) and its major metabolites, acetaldehyde and acetate, can directly modulate protein balance under in vitro conditions.
  
  
  METHODS
  Human myocytes were incubated with different doses of EtOH for varying periods of time (i.e., 4-72 hr). Alternatively, cells were incubated with acetaldehyde, acetate, insulin, insulin-like growth factor-I (IGF-I), or with a combination of EtOH plus insulin or IGF-I. Rates of protein synthesis or degradation were determined by 35S-methionine/cysteine incorporation into or release from cellular protein.
  
  
  RESULTS
  A significant, 15% to 20%, decrease in basal protein synthesis was observed after 24 hr, but not at earlier time points, in response to 80 mM EtOH. Incubation of myocytes for 72 hr decreased synthesis in cells incubated with EtOH ranging between 60 and 120 mM. The ability of IGF-I or insulin to stimulate protein synthesis was impaired by 30% and 60%, respectively, in cells incubated with 80 mM EtOH for 72 hr. Exposure of cells to 200 microM acetaldehyde or 5 mM Na-acetate also decreased basal protein synthesis. In contrast, neither EtOH, acetaldehyde, nor acetate altered the basal rate of protein degradation. However, EtOH completely impaired the ability of insulin and IGF-I to inhibit proteolysis. Finally, EtOH did not impair IGF-I receptor autophosphorylation, but inhibited the ability of insulin to phosphorylate its own receptor. EtOH also did not alter the number of insulin or IGF-I receptors or the formation of insulin/IGF-I hybrid receptors.
  
  
  CONCLUSIONS
  We have demonstrated that EtOH can directly inhibit muscle protein synthesis under in vitro conditions. Neither EtOH nor its metabolites altered basal protein degradation, although EtOH did compromise the ability of both insulin and IGF-I to slow proteolysis. This impairment seems to be mediated by different defects in signal transduction.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA. lqh10@psu.edu
authors.forename: L Q
authors.initials: LQ
authors.lastname: Hong-Brown
authors.forename: R A
authors.initials: RA
authors.lastname: Frost
authors.forename: C H
authors.initials: CH
authors.lastname: Lang
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D012313:RNA / Q000032:analysis; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000085:Acetates; D007328:Insulin; D009124:Muscle Proteins; D000431:Ethanol; D012313:RNA; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D000079:Acetaldehyde