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

Publication ,  Journal Article
Akimoto, T; Pohnert, SC; Li, P; Zhang, M; Gumbs, C; Rosenberg, PB; Williams, RS; Yan, Z
Published in: The Journal of biological chemistry
May 2005

Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) 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-1alpha 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-1alpha 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-1alpha 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-1alpha promoter activity was enhanced by increased expression of the downstream transcription factor ATF2 and completely blocked by ATF2DeltaN, a dominant negative ATF2. Skeletal muscle-specific expression of a constitutively active activator of p38, MKK6E, in transgenic mice resulted in enhanced Pgc-1alpha 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-1alpha gene expression and skeletal muscle adaptation.

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Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

May 2005

Volume

280

Issue

20

Start / End Page

19587 / 19593

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Physical Exertion
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Muscle, Skeletal
 

Citation

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Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., … Yan, Z. (2005). Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. The Journal of Biological Chemistry, 280(20), 19587–19593. https://doi.org/10.1074/jbc.m408862200
Akimoto, Takayuki, Steven C. Pohnert, Ping Li, Mei Zhang, Curtis Gumbs, Paul B. Rosenberg, R Sanders Williams, and Zhen Yan. “Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway.The Journal of Biological Chemistry 280, no. 20 (May 2005): 19587–93. https://doi.org/10.1074/jbc.m408862200.
Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, et al. Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. The Journal of biological chemistry. 2005 May;280(20):19587–93.
Akimoto, Takayuki, et al. “Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway.The Journal of Biological Chemistry, vol. 280, no. 20, May 2005, pp. 19587–93. Epmc, doi:10.1074/jbc.m408862200.
Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, Williams RS, Yan Z. Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. The Journal of biological chemistry. 2005 May;280(20):19587–19593.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

May 2005

Volume

280

Issue

20

Start / End Page

19587 / 19593

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Physical Exertion
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Muscle, Skeletal