PMID- 25257868 OWN - NLM STAT- MEDLINE DCOM- 20151015 LR - 20211203 IS - 1522-1601 (Electronic) IS - 8750-7587 (Print) IS - 0161-7567 (Linking) VI - 117 IP - 10 DP - 2014 Nov 15 TI - Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction. PG - 1170-9 LID - 10.1152/japplphysiol.00180.2014 [doi] AB - 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. CI - Copyright (c) 2014 the American Physiological Society. FAU - Steiner, Jennifer L AU - Steiner JL AD - Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania JLS1075@psu.edu. FAU - Lang, Charles H AU - Lang CH AD - Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania. LA - eng GR - F32 AA023422/AA/NIAAA NIH HHS/United States GR - R37-AA-011290/AA/NIAAA NIH HHS/United States GR - F32-AA-23422/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140925 PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Cell Cycle Proteins) RN - 0 (Eif4ebp1 protein, mouse) RN - 0 (Eukaryotic Initiation Factors) RN - 0 (Muscle Proteins) RN - 0 (Phosphoproteins) RN - 0 (Ribosomal Protein S6) RN - 0 (ribosomal protein S6, mouse) RN - 3K9958V90M (Ethanol) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) RN - EC 2.7.11.1 (Rps6ka1 protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Alcohol Drinking/*adverse effects MH - Animals MH - Carrier Proteins/metabolism MH - Cell Cycle Proteins MH - Electric Stimulation MH - Ethanol/blood/*toxicity MH - Eukaryotic Initiation Factors MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Hindlimb MH - Male MH - Mice, Inbred C57BL MH - Muscle Contraction MH - Muscle Proteins/*biosynthesis MH - Muscle, Skeletal/*drug effects/enzymology/innervation MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Ribosomal Protein S6/metabolism MH - Ribosomal Protein S6 Kinases, 90-kDa/metabolism MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/*metabolism MH - Time Factors PMC - PMC4233249 OTO - NOTNLM OT - 4E-binding protein OT - anabolic resistance OT - p70S6K1 OT - resistance exercise OT - skeletal muscle metabolism EDAT- 2014/09/27 06:00 MHDA- 2015/10/16 06:00 PMCR- 2015/11/15 CRDT- 2014/09/27 06:00 PHST- 2014/09/27 06:00 [entrez] PHST- 2014/09/27 06:00 [pubmed] PHST- 2015/10/16 06:00 [medline] PHST- 2015/11/15 00:00 [pmc-release] AID - japplphysiol.00180.2014 [pii] AID - JAPPL-00180-2014 [pii] AID - 10.1152/japplphysiol.00180.2014 [doi] PST - ppublish SO - J Appl Physiol (1985). 2014 Nov 15;117(10):1170-9. doi: 10.1152/japplphysiol.00180.2014. Epub 2014 Sep 25.