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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1999-2-26
|
| pubmed:abstractText |
1. We have previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31), without any further degradation products. In this study, we investigated the effect of synthetic ET-1 (1-31) on the proliferation of cultured human coronary artery smooth muscle cells (HCASMCs). 2. ET-1 (1-31) increased [3H]-thymidine incorporation and cell numbers to a similar extent as ET-1 at 100 nM. This ET-1 (1-31)-induced [3H]-thymidine uptake was not affected by phosphoramidon, an inhibitor of ET-converting enzyme. It was, however, inhibited by BQ123, an endothelin ET(A) receptor antagonist, but not by BQ788, an endothelin ET(B) receptor antagonist. 3. By using an in-gel kinase assay, we demonstrated that ET-1 (1-31) activated extracellular signal-regulated kinase 1/2 (ERK1/2) in a concentration-dependent manner (100 pM to 1 microM) in HCASMCs. ET-1 (1-31)-induced ERK1/2 activation was inhibited by BQ123, but not by BQ788 and phosphoramidon. Inhibition of protein kinase C (PKC) and ERK kinase also caused a reduction of ET-1 (1-31)-induced ERK1/2 activation, whereas tyrosine kinase inhibition had little effect. 4. Gel-mobility shift analysis revealed that the ERK1/2 activation was followed by an increase in transcription factor activator protein-1 DNA binding activity in HCASMCs. 5. Our results strongly suggest that ET-1 (1-31) itself stimulates HCASMC proliferation probably through endothelin ET(A) or ET(A)-like receptors. The underlining mechanism of cell growth by ET-1 (1-31) may be explained in part by PKC-dependent ERK1/2 activation. Since human chymase has been proposed to play a role in atherosclerosis, ET-1 (1-31) may be one of the mediators.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/endothelin-1 (1-31)
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0007-1188
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
125
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1019-27
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9846640-Arteries,
pubmed-meshheading:9846640-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9846640-Cell Division,
pubmed-meshheading:9846640-Cells, Cultured,
pubmed-meshheading:9846640-DNA-Binding Proteins,
pubmed-meshheading:9846640-Endothelin-1,
pubmed-meshheading:9846640-Endothelins,
pubmed-meshheading:9846640-Enzyme Activation,
pubmed-meshheading:9846640-Heart,
pubmed-meshheading:9846640-Humans,
pubmed-meshheading:9846640-MAP Kinase Kinase 1,
pubmed-meshheading:9846640-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:9846640-Muscle, Smooth, Vascular,
pubmed-meshheading:9846640-Peptide Fragments,
pubmed-meshheading:9846640-Protein Kinase C,
pubmed-meshheading:9846640-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9846640-Protein-Tyrosine Kinases,
pubmed-meshheading:9846640-Time Factors,
pubmed-meshheading:9846640-Transcription Factor AP-1
|
| pubmed:year |
1998
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| pubmed:articleTitle |
Effect of endothelin-1 (1-31) on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells.
|
| pubmed:affiliation |
Department of Pharmacology, The University of Tokushima School of Medicine, Japan.
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| pubmed:publicationType |
Journal Article
|