Stimulatory effect of ouabain on VCAM-1 and iNOS expression in murine endothelial cells: involvement of NF-kappa B.
Endothelial cells play a pivotal role in the development of atherosclerosis. An 'activated' phenotype of these cells is manifested by signal transduction-dependent expression of genes encoding cytokines, pro- and anticoagulant factors, and cell adhesion molecules. In the current study we examined the effect of ouabain, an inhibitor of Na+/K(+)-ATPase, on the process of endothelial cell activation. We demonstrated that ouabain was able to stimulate VCAM-1 expression and potentiate the effect of IFN-gamma on this process. Moreover, ouabain provided a complementary signal for either TNF or IFN-gamma in inducing iNOS expression. Our data also show, for the first time, that inhibition of Na+/K(+)-ATPase led to activation of the transcription factor, NF-kappa B, which may provide an explanation for the effects of ouabain on endothelial cells.
Institute of Molecular Biology, Jagiellonian University, Kraków, Poland.
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Cohen
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D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000098:blood supply; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D016328:NF-kappa B; D009573:Nitrites; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D010042:Ouabain; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase