title: Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania JLS1075@psu.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steiner
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D004558:Electric Stimulation; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006614:Hindlimb; D008297:Male; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039642:Eukaryotic Initiation Factors; D009124:Muscle Proteins; D010750:Phosphoproteins; D038601:Ribosomal Protein S6; C448579:ribosomal protein S6, mouse; D000431:Ethanol; C546843:mTOR protein, mouse; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 4E-binding protein; anabolic resistance; p70S6K1; resistance exercise; skeletal muscle metabolism