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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6899
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pubmed:dateCreated |
2002-8-15
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pubmed:abstractText |
The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Creatine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Creatine Kinase, MM Form,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Myogenic Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Myoglobin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Troponin I,
http://linkedlifedata.com/resource/pubmed/chemical/myocyte-specific enhancer-binding...,
http://linkedlifedata.com/resource/pubmed/chemical/peroxisome-proliferator-activated...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:Bassel-DubyRhondaR,
pubmed-author:BossOlivierO,
pubmed-author:EnkLL,
pubmed-author:IsotaniEijiE,
pubmed-author:LinJiandieJ,
pubmed-author:LowellBradford BBB,
pubmed-author:MichaelLaura FLF,
pubmed-author:OlsonEric NEN,
pubmed-author:PuigserverPereP,
pubmed-author:SpiegelmanBruce MBM,
pubmed-author:TarrPaul TPT,
pubmed-author:WuZhidanZ,
pubmed-author:ZhangChen-YuCY
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
418
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
797-801
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12181572-Animals,
pubmed-meshheading:12181572-Cell Line,
pubmed-meshheading:12181572-Creatine Kinase,
pubmed-meshheading:12181572-Creatine Kinase, MM Form,
pubmed-meshheading:12181572-DNA-Binding Proteins,
pubmed-meshheading:12181572-Electric Stimulation,
pubmed-meshheading:12181572-Isoenzymes,
pubmed-meshheading:12181572-Mice,
pubmed-meshheading:12181572-Mice, Transgenic,
pubmed-meshheading:12181572-Muscle, Skeletal,
pubmed-meshheading:12181572-Muscle Fatigue,
pubmed-meshheading:12181572-Muscle Fibers, Slow-Twitch,
pubmed-meshheading:12181572-Myogenic Regulatory Factors,
pubmed-meshheading:12181572-Myoglobin,
pubmed-meshheading:12181572-Promoter Regions, Genetic,
pubmed-meshheading:12181572-Transcription, Genetic,
pubmed-meshheading:12181572-Transcription Factors,
pubmed-meshheading:12181572-Transcriptional Activation,
pubmed-meshheading:12181572-Transgenes,
pubmed-meshheading:12181572-Troponin I
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pubmed:year |
2002
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pubmed:articleTitle |
Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.
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pubmed:affiliation |
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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