Excessive glucocorticoid-induced muscle MuRF1 overexpression is independent of Akt/FoXO1 pathway
Open Access
- 17 November 2017
- journal article
- Published by Portland Press Ltd. in Bioscience Reports
- Vol. 37 (6)
- https://doi.org/10.1042/bsr20171056
Abstract
The ubiquitin-proteasome system (UPS)-dependent proteolysis plays a major role in the muscle catabolic action of glucocorticoids (GCs). Atrogin-1 and muscle-specific RING finger protein 1 (MuRF1), two E3 ubiquitin ligases, are uniquely expressed in muscle. It has been previously demonstrated that GC treatment induced MuRF1 and atrogin-1 overexpression. However, it is yet unclear whether the higher pharmacological dose of GCs induced muscle protein catabolism through MuRF1 and atrogin-1. In the present study, the role of atrogin-1 and MuRF1 in C2C12 cells protein metabolism during excessive dexamethasone (DEX) was studied. The involvement of Akt/forkhead box O1 (FoXO1) signaling pathway and the cross-talk between anabolic regulator mammalian target of rapamycin (mTOR) and catabolic regulator FoXO1 were investigated. High concentration of DEX increased MuRF1 protein level in a time-dependent fashion (P0.05). FoXO1/3a (Thr24/32) phosphorylation was enhanced (PP0.05) by DEX. RU486 treatment inhibited the DEX-induced increase of FoXO1/3a phosphorylation (P0.05), but inhibited the activation of MuRF1 protein induced by DEX (PP<0.05).This publication has 49 references indexed in Scilit:
- PPARβ/δ Regulates Glucocorticoid- and Sepsis-Induced FOXO1 Activation and Muscle WastingPLOS ONE, 2013
- Rictor/mTORC2 Is Essential for Maintaining a Balance Between β-Cell Proliferation and Cell SizeDiabetes, 2011
- FoxO1 Haploinsufficiency Protects Against High-Fat Diet–Induced Insulin Resistance With Enhanced Peroxisome Proliferator–Activated Receptor γ Activation in Adipose TissueDiabetes, 2009
- Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptorBiochemical and Biophysical Research Communications, 2009
- The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 geneAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubesJournal of Cellular Biochemistry, 2008
- Mechanisms of glucocorticoid-induced myopathyJournal of Endocrinology, 2008
- Mechanisms of skeletal muscle atrophyCurrent Opinion in Rheumatology, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970