Enhancement of fibrinolytic activity of vascular endothelial cells by chaetoglobosin A, crinipellin B, geodin and triticone B.
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.
Shinohara
C
C
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Japan.
Chikanishi
T
T
Nakashima
S
S
Hashimoto
A
A
Hamanaka
A
A
Endo
A
A
Hasumi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005341:Fibrinolysin / Q000187:drug effects / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005658:Fungi / Q000378:metabolism; D026121:Indole Alkaloids; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology; D009930:Organic Chemicals; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011233:Precipitin Tests; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001572:Benzofurans; D005343:Fibrinolytic Agents; D026121:Indole Alkaloids; D007211:Indoles; D007769:Lactams; D009930:Organic Chemicals; D017395:Plasminogen Activator Inhibitor 1; C057767:triticone A; C052047:geodin; C019290:chaetoglobosins; C019306:crinipellin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator