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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-3-6
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pubmed:abstractText |
We have investigated the role of inhibitor kappaBalpha (IkappaBalpha) in the activation of nuclear factor kappaB (NF-kappaB) observed in human aortic endothelial cells (HAEC) undergoing a low shear stress of 2 dynes/cm(2). Low shear for 6 h resulted in a reduction of IkappaBalpha levels, an activation of NF-kappaB, and an increase in kappaB-dependent vascular cell adhesion molecule 1 (VCAM-1) mRNA expression and endothelial-monocyte adhesion. Overexpression of IkappaBalpha in HAEC attenuated all of these shear-induced responses. These results suggest that downregulation of IkappaBalpha is the major factor in the low shear-induced activation of NF-kappaB in HAEC. We then investigated the role of nitric oxide (NO) in the regulation of IkappaBalpha/NF-kappaB. Overexpression of endothelial nitric oxide synthase (eNOS) inhibited NF-kappaB activation in HAEC exposed to 6 h of low shear stress. Addition of the structurally unrelated NO donors S-nitrosoglutathione (300 microM) or sodium nitroprusside (1 mM) before low shear stress significantly increased cytoplasmic IkappaBalpha and concomitantly reduced NF-kappaB binding activity and kappaB-dependent VCAM-1 promoter activity. Together, these data suggest that NO may play a major role in the regulation of IkappaBalpha levels in HAEC and that the application of low shear flow increases NF-kappaB activity by attenuating NO generation and thus IkappaBalpha levels.
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pubmed:grant |
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pubmed:keyword |
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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/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NOS3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroprusside,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/S-nitroglutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0363-6143
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1039-47
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12620896-Aorta,
pubmed-meshheading:12620896-Cells, Cultured,
pubmed-meshheading:12620896-Down-Regulation,
pubmed-meshheading:12620896-Endothelium, Vascular,
pubmed-meshheading:12620896-Glutathione,
pubmed-meshheading:12620896-Humans,
pubmed-meshheading:12620896-I-kappa B Proteins,
pubmed-meshheading:12620896-NF-kappa B,
pubmed-meshheading:12620896-Nitric Oxide,
pubmed-meshheading:12620896-Nitric Oxide Donors,
pubmed-meshheading:12620896-Nitric Oxide Synthase,
pubmed-meshheading:12620896-Nitric Oxide Synthase Type III,
pubmed-meshheading:12620896-Nitro Compounds,
pubmed-meshheading:12620896-Nitroprusside,
pubmed-meshheading:12620896-Promoter Regions, Genetic,
pubmed-meshheading:12620896-RNA, Messenger,
pubmed-meshheading:12620896-Stress, Mechanical,
pubmed-meshheading:12620896-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2003
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pubmed:articleTitle |
IkappaBalpha-dependent regulation of low-shear flow-induced NF-kappa B activity: role of nitric oxide.
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pubmed:affiliation |
Department of Pathology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. mohan@uthscsa.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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