Next Article in Journal
Offspring Number Does Not Influence Reaching the Disability’s Milestones in Multiple Sclerosis: A Seven-Year Follow-Up Study
Previous Article in Journal
Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(2), 232; doi:10.3390/ijms17020232

Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

1
Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
2
Laboratory of Systems Physiology, Department of Kinesiology, University of North Carolina Charlotte, Charlotte, NC 28223, USA
*
Author to whom correspondence should be addressed.
Received: 15 January 2016 / Revised: 3 February 2016 / Accepted: 5 February 2016 / Published: 11 February 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2007 KB, uploaded 18 February 2016]   |  

Abstract

Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids. View Full-Text
Keywords: glucocorticoid receptor α 2; glucocorticoid receptor β 3; GRβ 4; GRα 5; atrophy 6; MAFbx 7; MuRF1 8; dexamethasone 9; myogenesis glucocorticoid receptor α 2; glucocorticoid receptor β 3; GRβ 4; GRα 5; atrophy 6; MAFbx 7; MuRF1 8; dexamethasone 9; myogenesis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Hinds, T.D., Jr.; Peck, B.; Shek, E.; Stroup, S.; Hinson, J.; Arthur, S.; Marino, J.S. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression. Int. J. Mol. Sci. 2016, 17, 232.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top