Abstract
We have recently demonstrated that NF-kappa B is involved in a thrombin-signaling and that the antisense oligodeoxynucleotides (ODNs) of NF-kappa B has a marked inhibitory effect on thrombin-induced cellular responses. In this study, we demonstrate that E5510 (4-cyano-5,5-bis(methoxyphenyl)-4-pentenoic acid), a compound with anti-platelet activity preferentially inhibits the thrombin-inducible NF-kappa B activation and then antagonizes the following thrombin-induced cellular responses, proliferation and cytokines production in vascular smooth muscle cell, and the adherency of differentiated HL-60 cells. These data suggest that E5510 is an anti-atherosclerotic or anti-restenotic drug induced by thrombin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Bacterial Proteins*
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Cell Adhesion / drug effects
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Cell Differentiation
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Cell Division / drug effects
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Cells, Cultured
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Cytokines / biosynthesis
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Fatty Acids, Monounsaturated / pharmacology*
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Humans
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Molecular Sequence Data
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Muscle, Smooth, Vascular / metabolism
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / physiology
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Platelet Aggregation Inhibitors / pharmacology*
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RNA-Binding Proteins / pharmacology
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Receptors, Thrombin / antagonists & inhibitors*
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Thrombin / antagonists & inhibitors
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Thrombin / pharmacology
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Transcription Factors / pharmacology
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Tumor Cells, Cultured
Substances
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Bacterial Proteins
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Cytokines
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Fatty Acids, Monounsaturated
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MtrB protein, Bacteria
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NF-kappa B
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Platelet Aggregation Inhibitors
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RNA-Binding Proteins
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Receptors, Thrombin
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Transcription Factors
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Thrombin
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Satigrel