Exercise stimulates Pgc-1α transcription in skeletal muscle through activation of the p38 MAPK pathway

Takayuki Akimoto, Steven C. Pohnert, Ping Li, Mei Zhang, Curtis Gumbs, Paul B. Rosenberg, R. Sanders Williams, Zhen Yan

Research output: Contribution to journalArticle

427 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) promotes mitochondrial biogenesis and slow fiber formation in skeletal muscle. We hypothesized that activation of the p38 mitogen-activated protein kinase (MAPK) pathway in response to increased muscle activity stimulated Pgc-1α gene transcription as part of the mechanisms for skeletal muscle adaptation. Here we report that a single bout of voluntary running induced a transient increase of Pgc-1α mRNA expression in mouse plantaris muscle, concurrent with an activation of the p38 MAPK pathway. Activation of the p38 MAPK pathway in cultured C2C12 myocytes stimulated Pgc-1α promoter activity, which could be blocked by the specific inhibitors of p38, SB203580 and SB202190, or a dominant negative p38. Furthermore, the p38-mediated increase in Pgc-1α promoter activity was enhanced by increased expression of the downstream transcription factor ATF2 and completely blocked by ATF2ΔN, a dominant negative ATF2. Skeletal muscle-specific expression of a constitutively active activator of p38, MKK6E, in transgenic mice resulted in enhanced Pgc-1α and cytochrome oxidase IV protein expression in fast-twitch skeletal muscles. These findings suggest that contractile activity-induced activation of the p38 MAPK pathway promotes Pgc-1α gene expression and skeletal muscle adaptation.

Original languageEnglish
Pages (from-to)19587-19593
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number20
DOIs
Publication statusPublished - 2005 May 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., Williams, R. S., & Yan, Z. (2005). Exercise stimulates Pgc-1α transcription in skeletal muscle through activation of the p38 MAPK pathway. Journal of Biological Chemistry, 280(20), 19587-19593. https://doi.org/10.1074/jbc.M408862200