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Author Notes:

E-mail: russ.price@emory.edu

Conceived and designed the experiments: JAR SRP BZ.

Performed the experiments: JAR BZ.

Analyzed the data: JAR BZ.

Contributed reagents/materials/analysis tools: SRP JAR MBH.

Wrote the paper: JAR SRP MEW MBH.

The authors thank Drs. Ben Perry, Harold Franch, James Bailey for their helpful discussions and Eugene Huang in the Department of Medicine Data Analytics and Biostatistics Core for his helpful advice.

The authors have declared that no competing interests exist.

The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.


Research Funding:

National Institutes of Health T32DK007656 to Jill A. Rahnert.

National Institutes of Health T32DK007656 to Matthew B. Hudson.

National Institutes of Health RO1DK95610 to S. Russ Price.

U.S. Department of Veterans Affairs I01BX001456 to S. Russ Price.

This work was supported by National Institutes of Health grants to SRP (RO1DK95610) and to JAR and MBH (T32DK007656), and a Merit Review Award from the US Department of Veterans Affairs Biomedical Development Laboratory Research and Development Service to SRP (I01BX001456).


  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics

Glucocorticoids Alter CRTC-CREB Signaling in Muscle Cells: Impact on PGC-1 alpha Expression and Atrophy Markers


Journal Title:



Volume 11, Number 7


, Pages e0159181-e0159181

Type of Work:

Article | Final Publisher PDF


Muscle wasting associated with chronic diseases has been linked to decreased expression of PGC-1α and overexpression of PGC-1α counters muscle loss. CREB, in conjunction with the CREB-regulated transcription coactivator (CRTC2), is a positive modulator of PGC-1α transcription. We previously reported that PGC-1α expression is decreased in skeletal muscle of diabetic rats despite a high level of CREB phosphorylation (i.e., activation), suggesting that CRTC2-CREB signaling may be dysregulated. In this study, the relationship between CREB/CRTC signaling and PGC-1α expression was examined in L6 myotubes treated with dexamethasone (Dex, 48h) to induce atrophy. Dex decreased PGC-1α mRNA and protein as well as the levels of CRTC1 and CRTC2 in the nucleus. Dex also altered the nuclear levels of two known regulators of CRTC2 localization; the amount of calcinuerin catalytic A subunit (CnA) was decreased whereas SIK was increased. To assess PGC-1α transcription, muscle cells were transfected with a PGC-1α luciferase reporter plasmid (PGC-1α-Luc). Dex suppressed PGC-1α luciferase activity while both isobutylmethylxanthine (IBMX) and over-expression of CRTC1 or CRTC2 increased PGC-1α-Luc activity. Mutation of the CRE binding site from PGC-1α-Luc reporter attenuated the responses to both IBMX and the CRTC proteins. Consistent with the reporter gene results, overexpression of CRTC2 produced an increase in CRTC2 in the nucleus and in PGC-1α mRNA and PGC-1α protein. Overexpression of CRTC2 was not sufficient to prevent the decrease in PGC-1α mRNA or protein by Dex. In summary, these data suggest that attenuated CREB/CRTC signaling contributes to the decrease in PGC-1α expression during atrophy.

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This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

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