Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor

Weidong Zhao, Weiping Qin, Jiangping Pan, Yong Wu, William A. Bauman, Christopher Cardozo

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The muscle ubiquitin ligases MAFbx and MuRF1 are upregulated in and promote muscle atrophy. Upregulation of MAFbx and MuRF1 by glucocorticoids has been linked to activation of FOXO1 and FOXO3A resulting from reduced Akt activity. We determined the requirements for the glucocorticoid receptor (GR) in these biological responses in C2C12 cells in which GR expression was knocked down by stable expression of an shRNA. Loss of GR prevented dexamethasone-induced increases in protein catabolism. Loss of GR, or inhibition of ligand binding to GR with RU486, prevented upregulation of MAFbx and MuRF1 by dexamethasone. Loss of GR also prevented dexamethasone-induced decreases in Akt phosphorylation, and increases in the fraction of FOXO1 that was unphosphorylated. The findings establish a requirement for the GR in activating molecular signals that promote muscle protein catabolism.

Original languageEnglish
Pages (from-to)668-672
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume378
Issue number3
DOIs
StatePublished - 16 Jan 2009

Keywords

  • Akt
  • Atrogin-1
  • FOXO1
  • Glucocorticoids
  • Glucocorticoiod receptor
  • MAFbx
  • MuRF1
  • Muscle atrophy

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