title: Acute Alcohol-Induced Decrease in Muscle Protein Synthesis in Female Mice Is REDD-1 and mTOR-Independent.
abstract: OBJECTIVE
  To determine the causative role of the REDD (regulated in development and DNA damage)-1 protein, a known negative regulator of mTOR kinase, in changes in muscle protein synthesis induced by acute alcohol administration.
  
  
  METHODS
  Adult female REDD1(-/-) or wild-type (WT) mice were injected IP with ethanol (alcohol; 3 g/kg BW) or saline and the skeletal muscle was removed 1 h later. In vivo protein synthesis was assessed as were selected endpoints related to the activation of mTOR and protein degradation.
  
  
  RESULTS
  Acute alcohol decreased muscle protein synthesis similarly in WT and REDD1(-/-) mice. In contrast, mTORC1 signaling was largely unaffected by either EtOH or genotype as evidenced by the lack of change in the phosphorylation of its downstream targets, S6K1 T(389) and 4E-BP1 S(65). Although alcohol decreased p62 and ULK1 S(757) protein in muscle from WT and REDD1(-/-) mice, there was no change in LC3B lipidation, or beclin1, Atg7 and Atg12 protein suggesting no change in autophagy. MuRF1 and atrogin-1 mRNAs were elevated in alcohol-treated REDD1(-/-) mice compared with WT mice suggesting activation of the ubiquitin proteasome activity. While there was no genotype or alcohol effect on plasma corticosterone, REDD1(-/-) mice failed to demonstrate the alcohol-induced hyperinsulinemia seen in WT mice.
  
  
  CONCLUSIONS
  REDD1 does not appear to play a role in the acute alcohol-mediated decrease in protein synthesis or mTOR activity, but may contribute to the regulation of ubiquitin-proteasome mediated protein breakdown.
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steiner
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Scot R
authors.initials: SR
authors.lastname: Kimball
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA clang@psu.edu.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006946:Hyperinsulinism / Q000139:chemically induced / Q000235:genetics; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C469992:Ddit4 protein, mouse; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D014157:Transcription Factors; D000431:Ethanol; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D003345:Corticosterone