Acute alcohol-induced decrease in muscle protein synthesis in female mice is REDD-1 and mTOR-independent

Jennifer L. Steiner, Scot R. Kimball, Charles H. Lang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Aims: 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)micewere injected IPwith ethanol (alcohol; 3 g/kg BW) or saline and the skeletalmusclewas removed 1 h later. In vivo protein synthesiswas 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 T389 and 4E-BP1 S65. Although alcohol decreased p62 and ULK1 S757 protein in muscle fromWTand 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 alcoholinduced hyperinsulinemia seen in WT mice. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)242-250
Number of pages9
JournalAlcohol and Alcoholism
Volume51
Issue number3
DOIs
StatePublished - May 1 2016

All Science Journal Classification (ASJC) codes

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

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