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rdf:type |
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lifeskim:mentions |
umls-concept:C0007578,
umls-concept:C0017262,
umls-concept:C0038836,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0225336,
umls-concept:C1419227,
umls-concept:C1456820,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2003-4-21
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pubmed:abstractText |
Oxidative signals play an important role in the regulation of endothelial cell adhesion molecule expression. Small GTP-binding protein Rac1 is activated by various proinflammatory substances and regulates superoxide generation in endothelial cells. In the present study, we demonstrate that adenoviral-mediated expression of dominant negative N17Rac1 (Ad.N17Rac1) suppresses tumor necrosis factor-alpha (TNF-alpha)-induced vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin gene expression in a dose-dependent manner. Ad.N17Rac1 did not inhibit TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) binding activity or inhibitor of NF-kappaB-alpha degradation. In contrast, Ad.N17Rac1 inhibited TNF-alpha-induced NF-kappaB-driven HIV(kappaB)(4)-CAT and p288VCAM-Luc promoter activity, suggesting that N17Rac1 inhibits TNF-alpha-induced VCAM-1, E-selectin, and ICAM-1 through suppressing NF-kappaB-mediated transactivation. In addition, expression of superoxide dismutase by adenovirus suppressed TNF-alpha-induced VCAM-1, E-selectin, and ICAM-1 mRNA accumulation. However, adenoviral-mediated expression of catalase only partially inhibited TNF-alpha-induced E-selectin gene expression and had no effect on VCAM-1 and ICAM-1 gene expression. These data suggest that Rac1 and superoxide play crucial roles in the regulation of expression of cell adhesion molecules in endothelial cells.
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pubmed:grant |
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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/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/E-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3565
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
305
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
573-80
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12606638-Adenoviridae,
pubmed-meshheading:12606638-Blotting, Northern,
pubmed-meshheading:12606638-Catalase,
pubmed-meshheading:12606638-Cell Adhesion Molecules,
pubmed-meshheading:12606638-Cell Nucleus,
pubmed-meshheading:12606638-Cells, Cultured,
pubmed-meshheading:12606638-Cytokines,
pubmed-meshheading:12606638-E-Selectin,
pubmed-meshheading:12606638-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:12606638-Endothelium, Vascular,
pubmed-meshheading:12606638-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:12606638-Genes, Reporter,
pubmed-meshheading:12606638-Humans,
pubmed-meshheading:12606638-Hydrogen Peroxide,
pubmed-meshheading:12606638-Intercellular Adhesion Molecule-1,
pubmed-meshheading:12606638-NF-kappa B,
pubmed-meshheading:12606638-Plasmids,
pubmed-meshheading:12606638-RNA, Messenger,
pubmed-meshheading:12606638-Reactive Oxygen Species,
pubmed-meshheading:12606638-Signal Transduction,
pubmed-meshheading:12606638-Stimulation, Chemical,
pubmed-meshheading:12606638-Superoxide Dismutase,
pubmed-meshheading:12606638-Superoxides,
pubmed-meshheading:12606638-Transfection,
pubmed-meshheading:12606638-Tumor Necrosis Factor-alpha,
pubmed-meshheading:12606638-Up-Regulation,
pubmed-meshheading:12606638-Vascular Cell Adhesion Molecule-1,
pubmed-meshheading:12606638-rac1 GTP-Binding Protein
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pubmed:year |
2003
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pubmed:articleTitle |
Rac1 and superoxide are required for the expression of cell adhesion molecules induced by tumor necrosis factor-alpha in endothelial cells.
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pubmed:affiliation |
Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. xchen@atherogenics.com
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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