Recombinant thrombomodulin inhibits thrombin-induced vascular endothelial growth factor production in neuronal cells.
Thrombin is a serine protease which is generated from its precursor prothrombin by the activation of the blood coagulation cascade. Thrombin converts fibrinogen to fibrin, activates platelets and several coagulation factors, and plays a central role in thrombosis and hemostasis by regulating platelet aggregation and blood coagulation. Here, we show that thrombn enhanced vascular endothelial growth factor (VEGF) production in a dose- and time-dependent manner in the supernatant of cultured PC-12 cells, as determined by enzyme-linked immunosorbent assay (ELISA). Thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) exerted an effect similar to thrombin on VEGF production. Thrombin-induced VEGF production was significantly attenuated by recombinant human thrombomodulin (rTM) and its minimal functional domain E456. Furthermore, the antioxidant N-acetyl-L-cysteine (NAC) markedly inhibited thrombin-induced VEGF production. Thus, rTM and NAC apparently inhibited the effect of thrombin on VEGF production in neuronal cells.
Sarker
K P
KP
Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. sar@khosp2.kufm.kagoshima-u.ac.jp
Yamahata
H
H
Nakata
M
M
Arisato
T
T
Nakajima
T
T
Kitajima
I
I
Maruyama
I
I
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018179:Receptors, Thrombin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018180:Thrombomodulin / Q000502:physiology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; D018180:Thrombomodulin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C072032:thrombin receptor peptide (42-55); D013917:Thrombin