[Study of signal transduction through thrombin receptor and anti-thrombotic strategy using its controls].
Thrombin, a key enzyme in the hemostatic pathway, also has various effects on the function of human platelet, endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC). A thrombin receptor (TR) has been cloned and is thought to mediate a variety of thrombin-induced responses. The post-receptor signals are mediated by several protein kinases responsible for NF-kappa B activation, and most thrombin-inducible genes have the kappa B sequence in the regulatory elements. TR stimulation resulted in a biphasic activation of NF-kappa B and the late phase of which required new NF-kappa B synthesis. We showed that the antisense oligodeoxynucleotides (ODNs) of NF-kappa B have a marked inhibitory effect on thrombin-induced cellular responses. Furthermore, E5510, a compound with anti-platelet activity preferentially inhibited the thrombin-inducible NF-kappa B activation. Therapeutic potential of inhibition of TR-NF-kappa B activation signaling for treatment with thrombotic disease is also indicated.
Kitajima
I
I
Department of Laboratory Medicine, Kagoshima University.
D001161:Arteriosclerosis / Q000628:therapy*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018179:Receptors, Thrombin / Q000502:physiology*; D015398:Signal Transduction; D013927:Thrombosis / Q000628:therapy*
D016328:NF-kappa B; D018179:Receptors, Thrombin