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p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice

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 controll...

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Autores principales: Pogozelski, Andrew R., Geng, Tuoyu, Li, Ping, Yin, Xinhe, Lira, Vitor A., Zhang, Mei, Chi, Jen-Tsan, Yan, Zhen
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775956/
https://www.ncbi.nlm.nih.gov/pubmed/19936205
http://dx.doi.org/10.1371/journal.pone.0007934
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author Pogozelski, Andrew R.
Geng, Tuoyu
Li, Ping
Yin, Xinhe
Lira, Vitor A.
Zhang, Mei
Chi, Jen-Tsan
Yan, Zhen
author_facet Pogozelski, Andrew R.
Geng, Tuoyu
Li, Ping
Yin, Xinhe
Lira, Vitor A.
Zhang, Mei
Chi, Jen-Tsan
Yan, Zhen
author_sort Pogozelski, Andrew R.
collection PubMed
description 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 p38γ mitogen-activated protein kinase (MAPK), but not p38α and p38β, 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 p38γ target genes, including peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) and vascular endothelial growth factor (Vegf), in skeletal muscle following motor nerve stimulation. Gene transfer-mediated overexpression of a dominant negative form of p38γ, but not that of p38α or p38β, blocked motor nerve stimulation-induced Pgc-1α transcription. These findings provide direct evidence for an obligated role of p38γ MAPK-PGC-1α regulatory axis in endurance exercise-induced metabolic adaptation, but not contractile adaptation, in skeletal muscle.
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spelling pubmed-27759562009-11-24 p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice Pogozelski, Andrew R. Geng, Tuoyu Li, Ping Yin, Xinhe Lira, Vitor A. Zhang, Mei Chi, Jen-Tsan Yan, Zhen PLoS One Research Article 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 p38γ mitogen-activated protein kinase (MAPK), but not p38α and p38β, 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 p38γ target genes, including peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) and vascular endothelial growth factor (Vegf), in skeletal muscle following motor nerve stimulation. Gene transfer-mediated overexpression of a dominant negative form of p38γ, but not that of p38α or p38β, blocked motor nerve stimulation-induced Pgc-1α transcription. These findings provide direct evidence for an obligated role of p38γ MAPK-PGC-1α regulatory axis in endurance exercise-induced metabolic adaptation, but not contractile adaptation, in skeletal muscle. Public Library of Science 2009-11-20 /pmc/articles/PMC2775956/ /pubmed/19936205 http://dx.doi.org/10.1371/journal.pone.0007934 Text en Pogozelski et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pogozelski, Andrew R.
Geng, Tuoyu
Li, Ping
Yin, Xinhe
Lira, Vitor A.
Zhang, Mei
Chi, Jen-Tsan
Yan, Zhen
p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title_full p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title_fullStr p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title_full_unstemmed p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title_short p38γ Mitogen-Activated Protein Kinase Is a Key Regulator in Skeletal Muscle Metabolic Adaptation in Mice
title_sort p38γ mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775956/
https://www.ncbi.nlm.nih.gov/pubmed/19936205
http://dx.doi.org/10.1371/journal.pone.0007934
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