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

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

Author information

1
Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania JLS1075@psu.edu.
2
Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania.

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.

KEYWORDS:

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

PMID:
25257868
PMCID:
PMC4233249
DOI:
10.1152/japplphysiol.00180.2014
[Indexed for MEDLINE]
Free PMC Article

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