Source:http://linkedlifedata.com/resource/pubmed/id/17540403
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-6-18
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pubmed:abstractText |
Prostacyclin (PGI2) and its analogues exert cardioprotective effects via the rhodopsin type membrane PGI2 receptor, IP. Peroxisome proliferator-activated receptor (PPAR) delta is a nuclear receptor abundantly expressed in cardiomyocytes and plays a pivotal role in maintaining constitutive mitochondrial fatty acid beta-oxidation (FAO). Recently, a novel signaling pathway of PGI2 via PPARdelta has been demonstrated in non-cardiac tissues. We therefore examined whether carbacyclin (cPGI2), a PGI2 analogue, up-regulates transcriptional expression of carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting enzyme in mitochondrial FAO, via PPARdelta in cardiomyocytes. Intraperitoneal injection of cPGI2 increased CPT-1 mRNA expression in murine hearts. Transcriptional activity was evaluated by PPAR responsive element (PPRE)-luciferase reporter gene assay in cultured neonatal rat cardiomyocytes. CPT-1 mRNA expression and PPRE promoter activity were significantly increased by cPGI2 in a concentration-dependent manner, where PPRE has been mapped to the promoter region of the CPT-1 gene. Moreover, the elevation of CPT-1 mRNA expression and PPRE promoter activity by cPGI2 was not abolished by H-89, a potent protein kinase A inhibitor, but was significantly inhibited in cardiomyocytes over-expressing a dominant-negative type of PPARdelta. Furthermore, electrophoretic mobility shift assays demonstrated that binding of PPARdelta to PPRE in the CPT-1 gene promoter is enhanced in response to cPGI2 stimulation. In addition, down-regulation of CPT-1 mRNA expression in cardiomyocytes subjected to hypoxia was attenuated by cPGI2. These results indicate that cPGI2 induces CPT-1 mRNA expression through PPARdelta, independent of the IP receptor signaling pathway, suggesting a possibility that cPGI2 modulates cardiac energy metabolism by activating FAO via PPARdelta.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carnitine O-Palmitoyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR delta,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/carboprostacyclin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2828
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pubmed:author |
pubmed-author:FujioYasushiY,
pubmed-author:HiramotoYoshimuneY,
pubmed-author:HirotaHisaoH,
pubmed-author:HoriMasatsuguM,
pubmed-author:KurodaTadashiT,
pubmed-author:MasakiMitsuruM,
pubmed-author:OkamotoKitaroK,
pubmed-author:ShioyamaWataruW,
pubmed-author:SugiyamaShokoS,
pubmed-author:Yamauchi-TakiharaKeikoK
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pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
54-62
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17540403-Animals,
pubmed-meshheading:17540403-Carnitine O-Palmitoyltransferase,
pubmed-meshheading:17540403-Cells, Cultured,
pubmed-meshheading:17540403-Enzyme Induction,
pubmed-meshheading:17540403-Epoprostenol,
pubmed-meshheading:17540403-Gene Expression Regulation,
pubmed-meshheading:17540403-Mice,
pubmed-meshheading:17540403-Mice, Inbred C57BL,
pubmed-meshheading:17540403-Myocytes, Cardiac,
pubmed-meshheading:17540403-PPAR delta,
pubmed-meshheading:17540403-Promoter Regions, Genetic,
pubmed-meshheading:17540403-RNA, Messenger,
pubmed-meshheading:17540403-Rats,
pubmed-meshheading:17540403-Receptors, Epoprostenol,
pubmed-meshheading:17540403-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
Carbacyclin induces carnitine palmitoyltransferase-1 in cardiomyocytes via peroxisome proliferator-activated receptor (PPAR) delta independent of the IP receptor signaling pathway.
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pubmed:affiliation |
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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