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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
1998-10-13
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pubmed:abstractText |
To explore the gene regulatory mechanisms involved in the metabolic control of cardiac fatty acid oxidative flux, the expression of muscle-type carnitine palmitoyltransferase I (M-CPT I) was characterized in primary cardiac myocytes in culture following exposure to the long-chain mono-unsaturated fatty acid, oleate. Oleate induced steady-state levels of M-CPT I mRNA 4.5-fold. The transcription of a plasmid construct containing the human M-CPT I gene promoter region fused to a luciferase gene reporter transfected into cardiac myocytes, was induced over 20-fold by long-chain fatty acid in a concentration-dependent and fatty acyl-chain length-specific manner. The M-CPT I gene promoter fatty acid response element (FARE-1) was localized to a hexameric repeat sequence located between 775 and 763 base pairs upstream of the initiator codon. Cotransfection experiments with expression vectors for the peroxisome proliferator-activated receptor alpha (PPARalpha) demonstrated that FARE-1 is a PPARalpha response element capable of conferring oleate-mediated transcriptional activation to homologous or heterologous promoters. Electrophoretic mobility shift assays demonstrated that PPARalpha bound FARE-1 with the retinoid X receptor alpha. The expression of M-CPT I in hearts of mice null for PPARalpha was approximately 50% lower than levels in wild-type controls. Moreover, a PPARalpha activator did not induce cardiac expression of the M-CPT I gene in the PPARalpha null mice. These results demonstrate that long-chain fatty acids regulate the transcription of a gene encoding a pivotal enzyme in the mitochondrial fatty acid uptake pathway in cardiac myocytes and define a role for PPARalpha in the control of myocardial lipid metabolism.
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pubmed:grant |
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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/Carnitine O-Palmitoyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Oleic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/etomoxir
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23786-92
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9726988-Animals,
pubmed-meshheading:9726988-Animals, Newborn,
pubmed-meshheading:9726988-Base Sequence,
pubmed-meshheading:9726988-Carnitine O-Palmitoyltransferase,
pubmed-meshheading:9726988-Cells, Cultured,
pubmed-meshheading:9726988-Cloning, Molecular,
pubmed-meshheading:9726988-Epoxy Compounds,
pubmed-meshheading:9726988-Fatty Acids, Nonesterified,
pubmed-meshheading:9726988-Genes, Reporter,
pubmed-meshheading:9726988-Humans,
pubmed-meshheading:9726988-Luciferases,
pubmed-meshheading:9726988-Mice,
pubmed-meshheading:9726988-Mice, Knockout,
pubmed-meshheading:9726988-Muscle, Skeletal,
pubmed-meshheading:9726988-Myocardium,
pubmed-meshheading:9726988-Oleic Acid,
pubmed-meshheading:9726988-Promoter Regions, Genetic,
pubmed-meshheading:9726988-RNA, Messenger,
pubmed-meshheading:9726988-Rats,
pubmed-meshheading:9726988-Rats, Sprague-Dawley,
pubmed-meshheading:9726988-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:9726988-Recombinant Fusion Proteins,
pubmed-meshheading:9726988-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:9726988-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:9726988-Transcription, Genetic,
pubmed-meshheading:9726988-Transcription Factors,
pubmed-meshheading:9726988-Transcriptional Activation,
pubmed-meshheading:9726988-Transfection
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pubmed:year |
1998
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pubmed:articleTitle |
Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha.
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pubmed:affiliation |
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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