estin and crinipellin

Four fungal metabolites, chaetoglobosin A (CGA), crinipellin B (CPB), geodin (GE) and triticone B (TTB), were found to enhance fibrinolytic activity of bovine aortic endothelial cells. Plasmin generation on the cells was elevated 2- to 4-fold when treated with these agents at a concentration of 3 approximately 100 microM. These effects were dependent on plasminogen and inhibited by anti-urokinase antibody. The effect of CGA, but not of CPB, GE and TTB, was abolished by cycloheximide. In a cell-free system, plasmin and urokinase activities as well as urokinase-catalyzed plasminogen activation were not enhanced by these agents. CGA, but not others, induced the production of urokinase in endothelial cells. CPB and GE accelerated plasminogen activator inhibitor- 1 (PAI-1) inactivation, and TTB caused direct, reversible inhibition of PAI-1. Thus, induction of urokinase by CGA and inhibition of PAI-1 by CPB, GE and TTB may, at least partly, account for the elevation of fibrinolytic activity of endothelial cells.

Topics: Animals; Anti-Bacterial Agents; Aorta; Benzofurans; Cattle; Cells, Cultured; Endothelium, Vascular; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Fungi; Indole Alkaloids; Indoles; Lactams; Organic Chemicals; Plasminogen Activator Inhibitor 1; Precipitin Tests; Urokinase-Type Plasminogen Activator