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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1998-9-17
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pubmed:abstractText |
We studied the role of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in epidermal growth factor (EGF)-induced prostacyclin (PGI2) production in cultured, spontaneously-beating neonatal ventricular rat cardiomyocytes. To this purpose, the effect of EGF on cardiomyocyte MAPK phosphorylation, MAPK activity and PGI2-production were investigated, and compared to those induced by the PKC activator 4 beta phorbol 12-myristate 13-acetate (PMA). Both EGF (0.1 microM) and PMA (0.1 microM) induced the rapid and reversible phosphorylation of 42 KDa-MAPK in ventricular cardiomyocytes, responses that were accompanied by transient increases in MAPK activity (190-230% of control values within 5 min), and two- to three-fold increases in PGI2 formation. The tyrosine kinase inhibitors lavendustin (1 microM) and genistein (10 microM) strongly inhibited EGF-induced MAPK activation and PGI2-formation, but had no effect on PMA-stimulated responses. Experiments with the PKC inhibitor CGP 41251 (1 microM) or with PKC-downregulated cells demonstrated that in contrast to the PMA-stimulated responses, EGF-induced MAPK activation and PGI2-production were PKC-independent processes. Investigating the role of MAPK in EGF- and in PMA-promoted PGI2-formation, we found that the MAPK-inhibitor 6-thioguanine (500 microM), as well as the MAPK-kinase-inhibitor PD98059 (50 microM) abolished both EGF- and PMA-stimulated PGI2-production in cardiomyocytes. Our results indicate that MAPK-activation is at the basis of both growth factor receptor and PKC-dependent eicosanoid-formation in ventricular cardiomyocytes, where EGF-induced prostaglandin-production takes place via a PKC-independent pathway.
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2828
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
933-45
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pubmed:dateRevised |
2008-8-20
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pubmed:meshHeading |
pubmed-meshheading:9618234-Analysis of Variance,
pubmed-meshheading:9618234-Animals,
pubmed-meshheading:9618234-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9618234-Cells, Cultured,
pubmed-meshheading:9618234-Enzyme Activation,
pubmed-meshheading:9618234-Epidermal Growth Factor,
pubmed-meshheading:9618234-Epoprostenol,
pubmed-meshheading:9618234-Heart Ventricles,
pubmed-meshheading:9618234-Phosphorylation,
pubmed-meshheading:9618234-Rats,
pubmed-meshheading:9618234-Rats, Wistar,
pubmed-meshheading:9618234-Tetradecanoylphorbol Acetate
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pubmed:year |
1998
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pubmed:articleTitle |
MAP kinase mediates epidermal growth factor- and phorbol ester-induced prostacyclin formation in cardiomyocytes.
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pubmed:affiliation |
Division of Endocrinology, University Hospital, Geneva, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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