PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes

Frontiers in Physiology

Anastasia Kralli¹  Craig R. Wright²  Patricio V. Sepulveda²  Erin L. Brown²  Victoria C. Foletta²  Paul Della Gatta²  Aaron P. Russell²  David Cameron-Smith³  Andrew Sanigorski⁴  Nicky Konstantopoulos⁴ 

[1] Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD, United States;Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, Australia;Liggins Institute, University of Auckland, Auckland, New Zealand;School of Medicine, Deakin University, Waurn Ponds, VIC, Australia;

关键词: PGC-1α;    PGC-1β;    ERRα;    protein synthesis;    C2C12 myotubes;    muscle mass;   

DOI  :  10.3389/fphys.2018.01336

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown