Regulation of the early expression of MAFbx/atrogin-1 and MuRF1 through membrane-initiated cortisol action in the skeletal muscle of rainbow trout

Daniela Aravena-Canales, Jorge E. Aedo, Alfredo Molina, Juan Antonio Valdés

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids are key stress-related hormones in vertebrates, with cortisol being the main glucocorticoid in teleosts. Glucocorticoids exert their effects through two mechanisms of action: genomic/classic and membrane initiated. In mammals, cortisol-mediated stress has been found to be associated with increased expression of critical atrophy-related genes (atrogenes), such as MAFbx/atrogin-1 and murf1/trim63. However, the direct impact of cortisol on the early regulation of atrogene expression in teleost skeletal muscle and the contribution of membrane-initiated cortisol action to this process have not been identified. In this work, the mRNA levels of atrogin-1 and murf1 were assessed in isolated myotubes and skeletal muscle of rainbow trout administered with cortisol or cortisol-BSA. This latter compound is a membrane-impermeable cortisol analog that exclusively induces membrane-initiated effects. We found that cortisol (10 mg/kg) first decreased the expression of both atrogenes at 3 h of treatment and then increased their expression at 9 h of treatment in the skeletal muscle of rainbow trout. Additionally, the in vitro analysis suggested that membrane-initiated cortisol action regulates murf1 but not atrogin-1 in rainbow trout myotubes. Using RU486 to selectively block glucocorticoid receptor (GR), we found that early downregulation of murf1 is potentially mediated by membrane GR signaling in myotubes. Considering the results of both the in vivo and in vitro approaches, we suggest that membrane-initiated cortisol action regulates the early expression of atrophy-related processes in teleosts.

Original languageEnglish
Article number110565
JournalComparative Biochemistry and Physiology Part - B: Biochemistry and Molecular Biology
Volume253
DOIs
Publication statusPublished - 1 Apr 2021

Keywords

  • Atrogenes
  • Cortisol
  • MAFbx/atrogin-1
  • murf1
  • Nongenomic cortisol signaling
  • Oncorhynchus mykiss
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

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