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PGC-1 alpha and PGC-1 beta increase protein synthesis via ERR alpha in C2C12 myotubes

Brown, Erin L, Foletta, Victoria C, Wright, Craig R, Sepulveda, Patricio V, Konstantopoulos, Nicky, Sanigorski, Andrew, Della Gatta, Paul, Cameron-Smith, David, Kralli, Anastasia and Russell, Aaron P 2018, PGC-1 alpha and PGC-1 beta increase protein synthesis via ERR alpha in C2C12 myotubes, Frontiers in physiology, vol. 9, pp. 1-17, doi: 10.3389/fphys.2018.01336.

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Title PGC-1 alpha and PGC-1 beta increase protein synthesis via ERR alpha in C2C12 myotubes
Formatted title PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes
Author(s) Brown, Erin L
Foletta, Victoria CORCID iD for Foletta, Victoria C orcid.org/0000-0002-5209-6134
Wright, Craig RORCID iD for Wright, Craig R orcid.org/0000-0001-7903-3144
Sepulveda, Patricio V
Konstantopoulos, Nicky
Sanigorski, AndrewORCID iD for Sanigorski, Andrew orcid.org/0000-0002-2858-4621
Della Gatta, PaulORCID iD for Della Gatta, Paul orcid.org/0000-0003-2231-8370
Cameron-Smith, David
Kralli, Anastasia
Russell, Aaron PORCID iD for Russell, Aaron P orcid.org/0000-0002-7323-9501
Journal name Frontiers in physiology
Volume number 9
Article ID 1336
Start page 1
End page 17
Total pages 17
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2018-09
ISSN 1664-042X
Keyword(s) PGC-1 alpha
PGC-1 beta
ERR alpha
protein synthesis
C2C12 myotubes
muscle mass
metabolism
resistance exercise
physiology
PGC-1α
PGC-1β
ERRα
science & technology
life sciences & biomedicine
Summary The transcriptional coactivators peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1α or PGC-1β overexpression in C2C12 myotubes increased protein synthesis and myotube diameter under basal conditions and attenuated the loss in protein synthesis following the treatment with the catabolic agent, dexamethasone. To investigate whether PGC-1α or PGC-1β signal through the Akt/mTOR pathway to increase protein synthesis, treatment with the PI3K and mTOR inhibitors, LY294002 and rapamycin, respectively, was undertaken but found unable to block PGC-1α or PGC-1β’s promotion of protein synthesis. Furthermore, PGC-1α and PGC-1β decreased phosphorylation of Akt and the Akt/mTOR substrate, p70S6K. In contrast to Akt/mTOR inhibition, the suppression of ERRα, a major effector of PGC-1α and PGC-1β activity, attenuated the increase in protein synthesis and myotube diameter in the presence of PGC-1α or PGC-1β overexpression. To characterize further the biological processes occurring, gene set enrichment analysis of genes commonly regulated by both PGC-1α and PGC-1β was performed following a microarray screen. Genes were found enriched in metabolic and mitochondrial oxidative processes, in addition to protein translation and muscle development categories. This suggests concurrent responses involving both increased metabolism and myotube protein synthesis. Finally, based on their known function or unbiased identification through statistical selection, two sets of genes were investigated in a human exercise model of stimulated protein synthesis to characterize further the genes influenced by PGC-1α and PGC-1β during physiological adaptive changes in skeletal muscle.
Language eng
DOI 10.3389/fphys.2018.01336
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, Brown, Foletta, Wright, Sepulveda, Konstantopoulos, Sanigorski, Della Gatta, Cameron-Smith, Kralli and Russell
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30114290

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.