title: Alcohol intoxication following muscle contraction in mice decreases muscle protein synthesis but not mTOR signal transduction.
abstract: BACKGROUND
  Alcohol (ethanol [EtOH]) intoxication antagonizes stimulation of muscle protein synthesis and mammalian target of rapamycin (mTOR) signaling. However, whether the anabolic response can be reversed when alcohol is consumed after the stimulus is unknown.
  
  
  METHODS
  A single bout of electrically stimulated muscle contractions (10 sets of 6 contractions) was induced in fasted male C57BL/6 mice 2 hours prior to alcohol intoxication. EtOH was injected intraperitoneally (3 g/kg), and the gastrocnemius/plantaris muscle complex was collected 2 hours later from the stimulated and contralateral unstimulated control leg.
  
  
  RESULTS
  Muscle contraction increased protein synthesis 28% in control mice, while EtOH abolished this stimulation-induced increase. Further, EtOH suppressed the rate of synthesis ~75% compared to control muscle irrespective of stimulation. This decrease was associated with impaired protein elongation as EtOH increased the phosphorylation of eEF2 Thr(56) . In contrast, stimulation-induced increases in mTOR protein complex-1 (mTORC1) (S6K1 Thr(421) /Ser(424) , S6K1 Thr(389) , rpS6 Ser(240/244) , and 4E-BP1 Thr(37/46) ) and mitogen-activated protein kinase (MAPK) (JNK Thr(183) /Tyr(185) , p38 Thr(180) /Tyr(182) , and rpS6S(235/236) ) signaling were not reversed by acute EtOH.
  
  
  CONCLUSIONS
  These data suggest that EtOH-induced decreases in protein synthesis in fasted mice may be independent of mTORC1 and MAPK signaling following muscle contraction and instead due to the antagonistic actions of EtOH on mRNA translation elongation. Therefore, EtOH suppresses the contraction-induced increase in protein synthesis, and over time has the potential to prevent skeletal muscle hypertrophy induced by repeated muscle contraction.
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steiner
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
mesh_terms: D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000187:drug effects*; D046912:Multiprotein Complexes / Q000096:biosynthesis* / Q000187:drug effects*; D009119:Muscle Contraction / Q000502:physiology*; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis* / Q000187:drug effects*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: Anabolic Signaling; Electrical Stimulation; Ethanol; S6K1; Skeletal Muscle Metabolism