Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction

J Appl Physiol (1985). 2014 Nov 15;117(10):1170-9. doi: 10.1152/japplphysiol.00180.2014. Epub 2014 Sep 25.


Alcohol (EtOH) decreases protein synthesis and mammalian target of rapamycin (mTOR)-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle. The purpose of the current investigation was to determine whether acute EtOH intoxication antagonizes the contraction-induced increase in protein synthesis and mTOR signaling in skeletal muscle. Fasted male mice were injected intraperitoneally with 3 g/kg EtOH or saline (control), and the right hindlimb was electrically stimulated (10 sets of 6 contractions). The gastrocnemius muscle complex was collected 30 min, 4 h, or 12 h after stimulation. EtOH decreased in vivo basal protein synthesis (PS) in the nonstimulated muscle compared with time-matched Controls at 30 min, 4 h, and 12 h. In Control, but not EtOH, PS was decreased 15% after 30 min. In contrast, PS was increased in Control 4 h poststimulation but remained unchanged in EtOH. Last, stimulation increased PS 10% in Control and EtOH at 12 h, even though the absolute rate remained reduced by EtOH. The stimulation-induced increase in the phosphorylation of S6K1 Thr(421)/Ser(424) (20-52%), S6K1 Thr(389) (45-57%), and its substrate rpS6 Ser(240/244) (37-72%) was blunted by EtOH at 30 min, 4 h, and 12 h. Phosphorylation of 4E-BP1 Ser(65) was also attenuated by EtOH (61%) at 4 h. Conversely, phosphorylation of extracellular signal-regulated kinase Thr(202)/Tyr(204) was increased by stimulation in Control and EtOH mice at 30 min but only in Control at 4 h. Our data indicate that acute EtOH intoxication suppresses muscle protein synthesis for at least 12 h and greatly impairs contraction-induced changes in synthesis and mTOR signaling.

Keywords: 4E-binding protein; anabolic resistance; p70S6K1; resistance exercise; skeletal muscle metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alcohol Drinking / adverse effects*
  • Animals
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Electric Stimulation
  • Ethanol / blood
  • Ethanol / toxicity*
  • Eukaryotic Initiation Factors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hindlimb
  • Male
  • Mice, Inbred C57BL
  • Muscle Contraction
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / innervation
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Ribosomal Protein S6 / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Muscle Proteins
  • Phosphoproteins
  • Ribosomal Protein S6
  • ribosomal protein S6, mouse
  • Ethanol
  • mTOR protein, mouse
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Rps6ka1 protein, mouse
  • TOR Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases