Exercise Stimulates Pgc-1α Transcription in Skeletal Muscle through Activation of the p38 MAPK Pathway
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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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The decrease in glycogen activates p38, which, like AMPK, can increase the transcription and activity of PGC-1α.
“The decrease in glycogen also activates the 38 kDa mitogen-activated protein kinase (p38), which, like AMPK, can increase the transcription and activity of PGC-1α [35–37].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [35]
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- Authors
- Akimoto, T., Pohnert, S. C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P. B., Williams, R. S., & Yan, Z.
- Affiliations
- Duke University (US)
- Corresponding author
- Yan, Zhen
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 280
- Issue
- 20
- Pages
- 19587-19593
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2048771411
- Cited by
- 714
- References
- 47
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 29 · 2023: 23 · 2022: 38 · 2021: 40 · 2020: 35 · 2019: 26 · 2018: 27 · 2017: 28 · 2016: 35 · 2015: 37 · 2014: 46 · 2013: 48 · 2012: 41
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PGC-1α, p38 MAPK pathway, skeletal muscle adaptation, voluntary running, mitochondrial biogenesis, ATF2, plantaris muscle, C2C12 myocytes, transcriptional regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Base Sequence, Cell Line, Electron Transport Complex IV, Physical Exertion, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Muscle Contraction, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transfection, Trans-Activators, Cyclic AMP Response Element-Binding Protein, DNA, Complementary, Muscle, Skeletal, Muscle Fibers, Skeletal, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 6, Mice, Activating Transcription Factor 2
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