Inhibitory Effect of a New Butadiene Derivative on the Production of Plasminogen Activator Inhibitor-1 in Cultured Bovine Endothelial Cells
| Autor: | Tamotsu Takagi, Jun Murakami, Yasuhiko Sasaki, Akio Ohtani, Ayako Hirano |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide medicine.medical_treatment Succinimides Benzylidene Compounds Biochemistry chemistry.chemical_compound Antigen Plasminogen Activator Inhibitor 1 Fibrinolysis Butadienes medicine Animals Zymography RNA Messenger Northern blot Molecular Biology Chemistry General Medicine Molecular biology Molecular Weight Endothelial stem cell Tissue Plasminogen Activator Plasminogen activator inhibitor-1 Cattle Endothelium Vascular Plasminogen activator |
| Zdroj: | Journal of Biochemistry. 120:1203-1208 |
| ISSN: | 0021-924X |
| DOI: | 10.1093/oxfordjournals.jbchem.a021542 |
| Popis: | Tissue-type plasminogen activator (t-PA) and its physiological inhibitor, plasminogen activator inhibitor-1 (PAI-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 PAI-1 production without affecting plasminogen activator (PA) synthesis in cultured bovine endothelial cells. T-686 (1-10 microM) 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-686 decreased the activities of PAI-1 with an M(r) of 55,000 and t-PA/PAI-1 complex with an M(r) 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 endothelial cells. |
| Databáze: | OpenAIRE |
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