Source:http://linkedlifedata.com/resource/pubmed/id/11463760
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-7-20
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| pubmed:abstractText |
The role of c-Src in growth signaling by angiotensin (Ang) II was investigated in vascular smooth muscle cells (VSMCs) from arteries of hypertensive patients. c-Src and extracellular signal-regulated kinase 1/2 (ERK1/2) activity, proto-oncogene expression, activating protein-1 (AP-1) DNA-binding activity, and DNA and protein synthesis were studied in Ang II-stimulated VSMCs derived from small peripheral resistance arteries of normotensive subjects (NTs, n=5) and age-matched untreated hypertensive patients (HTs, n=10). Ang II type 1 (AT(1)) and type 2 (AT(2)) receptor status was also assessed. Ang II dose-dependently increased the synthesis of DNA and protein, with enhanced effects in VSMCs from HTs. PD 098,059, a selective inhibitor of the ERK1/2 pathway, attenuated Ang II-stimulated growth in HTs. The effects of PD 098,059 were greater in HTs than in NTs. In NTs, Ang II transiently increased ERK1/2 phosphorylation, whereas in HTs, Ang II-stimulated actions were augmented and sustained. PP2, a selective Src inhibitor, reduced ERK1/2 activity and normalized ERK1/2 responses in HTs. Ang II-induced c-Src phosphorylation was 2- to 3-fold greater in HTs than in NTs. In HTs but not NTs, kinase activation was followed by overexpression of c-fos and enhanced AP-1 DNA-binding activity. PD 098,059 and PP2 attenuated these responses. AT(1) receptor expression was similar in NTs and HTs. In HT cells transfected with c-fos antisense oligodeoxynucleotide, Ang II-stimulated growth was reduced compared with sense oligodeoxynucleotide. Our findings suggest that augmented Ang II-stimulated VSMC growth is mediated via hyperactivation of c-Src-regulated ERK1/2-dependent pathways, leading to overexpression of c-fos mRNA and enhanced AP-1 DNA-binding activity. Because AT(1) receptor expression was unaltered in HTs, increased Ang II signaling may be a postreceptor phenomenon. These data define a signal transduction pathway whereby Ang II mediates exaggerated growth in VSMCs from HTs.
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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/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein pp60(v-src),
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Angiotensin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1524-4563
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
38
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
56-64
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11463760-Adult,
pubmed-meshheading:11463760-Aged,
pubmed-meshheading:11463760-Angiotensin II,
pubmed-meshheading:11463760-Cell Division,
pubmed-meshheading:11463760-DNA,
pubmed-meshheading:11463760-Gene Expression,
pubmed-meshheading:11463760-Humans,
pubmed-meshheading:11463760-Hypertension,
pubmed-meshheading:11463760-Middle Aged,
pubmed-meshheading:11463760-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11463760-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:11463760-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11463760-Muscle, Smooth, Vascular,
pubmed-meshheading:11463760-Oligodeoxyribonucleotides, Antisense,
pubmed-meshheading:11463760-Oncogene Protein pp60(v-src),
pubmed-meshheading:11463760-Phosphorylation,
pubmed-meshheading:11463760-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:11463760-Receptor, Angiotensin, Type 1,
pubmed-meshheading:11463760-Receptor, Angiotensin, Type 2,
pubmed-meshheading:11463760-Receptors, Angiotensin,
pubmed-meshheading:11463760-Signal Transduction,
pubmed-meshheading:11463760-Transcription Factor AP-1
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| pubmed:year |
2001
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| pubmed:articleTitle |
Src is an important mediator of extracellular signal-regulated kinase 1/2-dependent growth signaling by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients.
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| pubmed:affiliation |
Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada. touyzr@ircm.qc.ca
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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