caa a22 4500 397555466 CHVBK 20180308164800.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021542 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021542 Inhibitory Effect of a New Butadiene Derivative on the Production of Plasminogen Activator Inhibitor-1 in Cultured Bovine Endothelial Cells [Elektronische Daten] [Akio Ohtani, Tamotsu Takagi, Jun Murakami, Yasuhiko Sasaki] Tissue-type plasminogen activator (t-PA) and its physiological inhibitor, plasminogen activator inhibitor-1 (PM-1), are known to be synthesized by vascular endothelial cells and to play important roles in regulating the fibrinolytic activity of plasma. We found that a new butadiene derivative, (3E,4E)-3-benzylidene-4-(3,4,5-trimethoxybenzylidene)pyrrolidine-2,5-dione (T-686), inhibits PM-1 production without affecting plasminogen activator (PA) synthesis in cultured bovine endothelial cells. T-688 (1-10 μM) dose-dependently decreased the accumulation of PAI-1 in conditioned medium from the treated cells and elevated PA activity in the conditioned medium. Analysis of the conditioned medium by the zymography technique indicated that T-688 decreased the activities of PAI-1 with an Mr of 55,000 and t-PA/PAI-1 complex with an Mr of 99,000. Furthermore, T-686 attenuated the augmentation of PAI-1 antigen induced by lipopolysaccharide in the conditioned medium. The decrease of PAI-1 antigen was in parallel with the reduction of the PAI-1 mRNA level (Northern blots). These results suggest that T-686 can promote net fibrinolytic activity through suppression of PAI-1 production without affecting PA elaboration in endothellal cells. © 1996 BY THE JOURNAL OF BIOCHEMISTRY Regular Papers nationallicence endothelial cell nationallicence fibrinolysis nationallicence plasminogen activator nationallicence plasminogen activator inhibitor-1 nationallicence T-686 nationallicence Ohtani Akio Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut Takagi Tamotsu Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut Murakami Jun Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut Sasaki Yasuhiko Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut The Journal of Biochemistry Oxford University Press 120/6(1996-12), 1203-1208 0021-924X 120:6<1203 1996 120 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021542 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021542 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ohtani Akio Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut NATIONALLICENCE 700 1- Takagi Tamotsu Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut NATIONALLICENCE 700 1- Murakami Jun Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut NATIONALLICENCE 700 1- Sasaki Yasuhiko Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,2-2-50 Kawagishi, Toda, Saitoma 335 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 120/6(1996-12), 1203-1208 0021-924X 120:6<1203 1996 120 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford