PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes

Erin L. Brown, Victoria C. Foletta, Craig R. Wright, Patricio V. Sepulveda, Nicky Konstantopoulos, Andrew Sanigorski, Paul Della Gatta, David Cameron-Smith, Anastasia Kralli, Aaron P. Russell

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number1336
JournalFrontiers in Physiology
Volume9
Issue numberSEP
DOIs
StatePublished - Sep 25 2018

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Skeletal Muscle Fibers
Proteins
Genes
Skeletal Muscle
70-kDa Ribosomal Protein S6 Kinases
Biological Phenomena
Peroxisome Proliferator-Activated Receptors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Muscle Development
Protein Biosynthesis
Sirolimus
Phosphatidylinositol 3-Kinases
Energy Metabolism
Dexamethasone
Phosphorylation
Muscles
Growth

Keywords

  • C2C12 myotubes
  • ERRα
  • Metabolism
  • Muscle mass
  • PGC-1α
  • PGC-1β
  • Protein synthesis
  • Resistance exercise

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Brown, E. L., Foletta, V. C., Wright, C. R., Sepulveda, P. V., Konstantopoulos, N., Sanigorski, A., ... Russell, A. P. (2018). PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes. Frontiers in Physiology, 9(SEP), [1336]. https://doi.org/10.3389/fphys.2018.01336

PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes. / Brown, Erin L.; Foletta, Victoria C.; Wright, Craig R.; Sepulveda, Patricio V.; Konstantopoulos, Nicky; Sanigorski, Andrew; Gatta, Paul Della; Cameron-Smith, David; Kralli, Anastasia; Russell, Aaron P.

In: Frontiers in Physiology, Vol. 9, No. SEP, 1336, 25.09.2018.

Research output: Contribution to journalArticle

Brown, EL, Foletta, VC, Wright, CR, Sepulveda, PV, Konstantopoulos, N, Sanigorski, A, Gatta, PD, Cameron-Smith, D, Kralli, A & Russell, AP 2018, 'PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes', Frontiers in Physiology, vol. 9, no. SEP, 1336. https://doi.org/10.3389/fphys.2018.01336
Brown EL, Foletta VC, Wright CR, Sepulveda PV, Konstantopoulos N, Sanigorski A et al. PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes. Frontiers in Physiology. 2018 Sep 25;9(SEP). 1336. https://doi.org/10.3389/fphys.2018.01336
Brown, Erin L. ; Foletta, Victoria C. ; Wright, Craig R. ; Sepulveda, Patricio V. ; Konstantopoulos, Nicky ; Sanigorski, Andrew ; Gatta, Paul Della ; Cameron-Smith, David ; Kralli, Anastasia ; Russell, Aaron P. / PGC-1α and PGC-1β increase protein synthesis via ERRα in C2C12 myotubes. In: Frontiers in Physiology. 2018 ; Vol. 9, No. SEP.
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AU - Konstantopoulos, Nicky

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