Source:http://linkedlifedata.com/resource/pubmed/id/10205148
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
1999-4-30
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| pubmed:abstractText |
Endothelial cells (ECs) exposed to cyclic strain induce gene expression. To elucidate the signaling mechanisms involved, we studied the effects of cyclic strain on ECs by using early growth response-1 (Egr-1) as a target gene. Cyclic strain induced a transient increase of Egr-1 mRNA levels that resulted in an increase of binding of nuclear proteins to the Egr-1 binding sequences in the platelet-derived growth factor-A promoter region. ECs subjected to strain enhanced Egr-1 transcription as revealed by promoter activities. Catalase pretreatment inhibited this induction. ECs, transfected with a dominant positive mutant of Ras (RasL61), increased Egr-1 promoter activities. In contrast, transfection with a dominant negative mutant of Ras (RasN17) attenuated this strain inducibility. ECs transfected with a dominant negative mutant of Raf-1 (Raf301) or the catalytically inactive mutant of extracellular signal-regulated kinase (ERK)-2 (mERK2) diminished strain-induced promoter activities. However, little effect on strain inducibility was observed in ECs transfected with a dominant negative mutant of Rac (RacN17) or a catalytically inactive mutant of JNK (JNK[K-R]). Consistently, strain-induced Egr-1 expression was inhibited after ECs were treated with a specific inhibitor (PD98059) to mitogen-activated protein kinase kinase. Moreover, strain to ECs induced mitogen-activated protein kinase/ERK activity. The activation of the ERK pathway was further substantiated by an increase of strain-induced transcriptional activity of Elk1, an ERK substrate. This strain-induced ERK activity was attenuated after ECs were treated with N-acetylcysteine or catalase. Consequently, this Egr-1 gene induction was abolished after ECs were treated with N-acetylcysteine or catalase. Deletion analyses of the promoter region (-698 bp) indicated that cyclic strain and H2O2 shared a common serum response element. Our data clearly indicate that cyclic strain-induced Egr-1 expression is mediated mainly via the Ras/Raf-1/ERK pathway and that strain-induced reactive oxygen species can modulate Egr-1 expression at least partially via this signaling 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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
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/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Response Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
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 |
Apr
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| pubmed:issn |
0009-7330
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
16
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| pubmed:volume |
84
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
804-12
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10205148-Animals,
pubmed-meshheading:10205148-Aorta,
pubmed-meshheading:10205148-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10205148-Cattle,
pubmed-meshheading:10205148-Cells, Cultured,
pubmed-meshheading:10205148-DNA-Binding Proteins,
pubmed-meshheading:10205148-Endothelium, Vascular,
pubmed-meshheading:10205148-Extracellular Space,
pubmed-meshheading:10205148-Gene Expression,
pubmed-meshheading:10205148-Genes, Reporter,
pubmed-meshheading:10205148-Hydrogen Peroxide,
pubmed-meshheading:10205148-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:10205148-Nuclear Proteins,
pubmed-meshheading:10205148-Platelet-Derived Growth Factor,
pubmed-meshheading:10205148-Promoter Regions, Genetic,
pubmed-meshheading:10205148-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:10205148-RNA, Messenger,
pubmed-meshheading:10205148-Reactive Oxygen Species,
pubmed-meshheading:10205148-Serum Response Factor,
pubmed-meshheading:10205148-Signal Transduction,
pubmed-meshheading:10205148-Transcription Factors,
pubmed-meshheading:10205148-Transcriptional Activation,
pubmed-meshheading:10205148-Zinc Fingers,
pubmed-meshheading:10205148-ras Proteins
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| pubmed:year |
1999
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| pubmed:articleTitle |
Modulation of Ras/Raf/extracellular signal-regulated kinase pathway by reactive oxygen species is involved in cyclic strain-induced early growth response-1 gene expression in endothelial cells.
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| pubmed:affiliation |
Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, and Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan, ROC.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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