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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1999-9-2
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pubmed:abstractText |
Endothelial cells (ECs) subjected to shear stress constantly release nitric oxide (NO). The effect of NO on shear stress-induced endothelial responses was examined. ECs subjected to shear stress induced a transient and shear force-dependent increase in early growth response-1 (Egr-1) mRNA levels. Treatment of ECs with an NO donor, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholinosydnonimine (SIN-1), inhibited this shear stress-induced Egr-1 expression. Conversely, an NO synthase inhibitor to ECs, N(G)-monomethyl-L-arginine, augmented this Egr-1 expression. NO modulation of Egr-1 expression was demonstrated by functional analysis of Egr-1 promoter activity using a chimera containing the Egr-1 promoter region (-698 bp) and reporter gene luciferase. In contrast to the enhanced promoter activity after N(G)-monomethyl-L-arginine treatment, shear stress-induced Egr-1 promoter activity was attenuated after ECs were treated with an NO donor. ECs cotransfected with a dominant negative mutant of Ras (RasN17), Raf-1 (Raf301), or a catalytically inactive mutant of extracellular signal-regulated kinase (ERK)-2 (mERK) inhibited shear stress-induced Egr-1 promoter activity. NO modulation of the signaling pathway was shown by its inhibitory effect on shear stress-induced ERK1/ERK2 phosphorylation and activity. This inhibitory effect was further substantiated by the inhibition of NO on both the shear stress-induced transcriptional activity of Elk-1 (an ERK substrate) and the promoter activity of a reporter construct containing serum response element. NO-treated ECs resulted in a reduction of binding of nuclear proteins to the Egr-1 binding sequences in the platelet-derived growth factor-A promoter region. These results indicate that shear stress-induced Egr-1 expression is modulated by NO via the ERK signaling pathway in ECs. Our findings support the importance of NO as a negative regulator in endothelial responses to hemodynamic forces.
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ELK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor A,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0009-7330
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
238-46
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10436166-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10436166-Cells, Cultured,
pubmed-meshheading:10436166-DNA-Binding Proteins,
pubmed-meshheading:10436166-Early Growth Response Protein 1,
pubmed-meshheading:10436166-Endothelium, Vascular,
pubmed-meshheading:10436166-Gene Expression,
pubmed-meshheading:10436166-Genes, Reporter,
pubmed-meshheading:10436166-Humans,
pubmed-meshheading:10436166-Immediate-Early Proteins,
pubmed-meshheading:10436166-Nitric Oxide,
pubmed-meshheading:10436166-Phosphorylation,
pubmed-meshheading:10436166-Platelet-Derived Growth Factor,
pubmed-meshheading:10436166-Promoter Regions, Genetic,
pubmed-meshheading:10436166-Proto-Oncogene Proteins,
pubmed-meshheading:10436166-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:10436166-RNA, Messenger,
pubmed-meshheading:10436166-Stress, Mechanical,
pubmed-meshheading:10436166-Time Factors,
pubmed-meshheading:10436166-Transcription, Genetic,
pubmed-meshheading:10436166-Transcription Factors,
pubmed-meshheading:10436166-ets-Domain Protein Elk-1,
pubmed-meshheading:10436166-ras Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
Nitric oxide regulates shear stress-induced early growth response-1. Expression via the extracellular signal-regulated kinase pathway in endothelial cells.
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pubmed:affiliation |
Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taiwan University, Taipei, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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