Alcohol Intoxication Following Muscle Contraction in Mice Decreases Muscle Protein Synthesis But Not mTOR Signal Transduction

Jennifer L. Steiner, Charles H. Lang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 Thr56. In contrast, stimulation-induced increases in mTOR protein complex-1 (mTORC1) (S6K1 Thr421/Ser424, S6K1 Thr389, rpS6 Ser240/244, and 4E-BP1 Thr37/46) and mitogen-activated protein kinase (MAPK) (JNK Thr183/Tyr185, p38 Thr180/Tyr182, and rpS6S235/236) 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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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