Dataset Information

PGC-1? and PGC-1? Increase Protein Synthesis via ERR? in C2C12 Myotubes.

ABSTRACT: The transcriptional coactivators peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) and PGC-1? 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-1? or PGC-1? 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-1? or PGC-1? 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-1? or PGC-1?'s promotion of protein synthesis. Furthermore, PGC-1? and PGC-1? decreased phosphorylation of Akt and the Akt/mTOR substrate, p70S6K. In contrast to Akt/mTOR inhibition, the suppression of ERR?, a major effector of PGC-1? and PGC-1? activity, attenuated the increase in protein synthesis and myotube diameter in the presence of PGC-1? or PGC-1? overexpression. To characterize further the biological processes occurring, gene set enrichment analysis of genes commonly regulated by both PGC-1? and PGC-1? 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-1? and PGC-1? during physiological adaptive changes in skeletal muscle.

SUBMITTER: Brown EL

PROVIDER: S-EPMC6190860 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Brown Erin L EL Foletta Victoria C VC Wright Craig R CR Sepulveda Patricio V PV Konstantopoulos Nicky N Sanigorski Andrew A Della Gatta Paul P Cameron-Smith David D Kralli Anastasia A Russell Aaron P AP

Frontiers in physiology 20180925

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 t ...[more]

PMID: 30356878

Similar Datasets

Project description:Background/objectivesPeroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells.Materials/methodsC2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay.ResultsGPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2.ConclusionsThe results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Dataset Information

PGC-1? and PGC-1? Increase Protein Synthesis via ERR? in C2C12 Myotubes.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets