Inhibition of plasminogen activator inhibitor-1 by 11-keto-9(E),12(E)-octadecadienoic acid, a novel fatty acid produced by Trichoderma sp.
We have recently found a novel fatty acid, 11-keto-9(E),12(E)-octadecadienoic acid (KOD), that enhances fibrinolytic activity of endothelial cells. The mechanism of action of KOD has been investigated. KOD increased 2-fold the plasmin activity of bovine aortic endothelial cells at 250 microM. The stimulation was dependent on plasminogen and was inhibited by anti-urokinase, whereas KOD did not enhance the urokinase-catalyzed plasminogen activation and the resulting plasmin activity in a cell-free system. Neither the production of urokinase nor the conversion of pro-urokinase to the active, two-chain form was elevated by KOD, but it decreased plasminogen activator inhibitor-1 (PAI-1) activity of cells and inactivated PAI-1 irreversibly in a purified system. These results demonstrated that the KOD enhancement of endothelial fibrinolytic activity was mediated, at least in part, by inactivation of PAI-1.
Chikanishi
T
T
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Japan.
Shinohara
C
C
Kikuchi
T
T
Endo
A
A
Hasumi
K
K
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D014242:Trichoderma / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C119341:11-keto-9(E),12(E)-octadecadienoic acid; D005227:Fatty Acids; D008041:Linoleic Acids; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator