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p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice.

Publication ,  Journal Article
Pogozelski, AR; Geng, T; Li, P; Yin, X; Lira, VA; Zhang, M; Chi, J-T; Yan, Z
Published in: PLoS One
November 20, 2009

Regular endurance exercise induces skeletal muscle contractile and metabolic adaptations, conferring salutary health benefits, such as protection against the metabolic syndrome. The plasticity of skeletal muscle has been extensively investigated, but how the adaptive processes are precisely controlled is largely unknown. Using muscle-specific gene deletion in mice, we now show that p38gamma mitogen-activated protein kinase (MAPK), but not p38alpha and p38beta, is required for endurance exercise-induced mitochondrial biogenesis and angiogenesis, whereas none of the p38 isoforms are required for IIb-to-IIa fiber-type transformation. These phenotypic findings were further supported by microarray and real-time PCR analyses revealing contractile activity-dependent p38gamma target genes, including peroxisome proliferator-activated receptor gamma co-activator-1alpha (Pgc-1alpha) and vascular endothelial growth factor (Vegf), in skeletal muscle following motor nerve stimulation. Gene transfer-mediated overexpression of a dominant negative form of p38gamma, but not that of p38alpha or p38beta, blocked motor nerve stimulation-induced Pgc-1alpha transcription. These findings provide direct evidence for an obligated role of p38gamma MAPK-PGC-1alpha regulatory axis in endurance exercise-induced metabolic adaptation, but not contractile adaptation, in skeletal muscle.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

November 20, 2009

Volume

4

Issue

11

Start / End Page

e7934

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vascular Endothelial Growth Factor A
  • Transcription Factors
  • Trans-Activators
  • Protein Isoforms
  • Physical Conditioning, Animal
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Oligonucleotide Array Sequence Analysis
  • Neovascularization, Pathologic
  • Muscle, Skeletal
 

Citation

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ICMJE
MLA
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Pogozelski, A. R., Geng, T., Li, P., Yin, X., Lira, V. A., Zhang, M., … Yan, Z. (2009). p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PLoS One, 4(11), e7934. https://doi.org/10.1371/journal.pone.0007934
Pogozelski, Andrew R., Tuoyu Geng, Ping Li, Xinhe Yin, Vitor A. Lira, Mei Zhang, Jen-Tsan Chi, and Zhen Yan. “p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice.PLoS One 4, no. 11 (November 20, 2009): e7934. https://doi.org/10.1371/journal.pone.0007934.
Pogozelski AR, Geng T, Li P, Yin X, Lira VA, Zhang M, et al. p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PLoS One. 2009 Nov 20;4(11):e7934.
Pogozelski, Andrew R., et al. “p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice.PLoS One, vol. 4, no. 11, Nov. 2009, p. e7934. Pubmed, doi:10.1371/journal.pone.0007934.
Pogozelski AR, Geng T, Li P, Yin X, Lira VA, Zhang M, Chi J-T, Yan Z. p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice. PLoS One. 2009 Nov 20;4(11):e7934.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

November 20, 2009

Volume

4

Issue

11

Start / End Page

e7934

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vascular Endothelial Growth Factor A
  • Transcription Factors
  • Trans-Activators
  • Protein Isoforms
  • Physical Conditioning, Animal
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Oligonucleotide Array Sequence Analysis
  • Neovascularization, Pathologic
  • Muscle, Skeletal