E5510 antagonizes thrombin receptor signals by inhibiting NF-kappa B activation.
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.
Nakajima
T
T
Department of Laboratory Medicine, Faculty of Medicine, University of Kagoshima, Japan.
Kitajima
I
I
Shin
H
H
Matsumoto
W
W
Soejima
Y
Y
Maruyama
I
I
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; C079092:MtrB protein, Bacteria; D016328:NF-kappa B; D010975:Platelet Aggregation Inhibitors; D016601:RNA-Binding Proteins; D018179:Receptors, Thrombin; D014157:Transcription Factors; D013917:Thrombin; C054678:Satigrel