The dexamethasone-induced inhibitor of fibrinolytic activity in hepatoma cells. A cellular product which specifically inhibits plasminogen activation

Dexamethasone induces an inhibitor of plasminogen-dependent fibrinolysis in rat hepatoma (HTC) cells. The specificity of the inhibitor for urokinase and plasmin was investigated using both fibrinolytic and esterolytic assays. Urokinase, but not plasmin, was inhibited by serum-free conditioned medium...

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Bibliographic Details
Published in:The Journal of biological chemistry 1982-04, Vol.257 (8), p.4260-4264
Main Authors: Coleman, P L, Barouski, P A, Gelehrter, T D
Format: Article
Language:English
Subjects:
Animals
Cell Line
Culture Media
Dexamethasone - pharmacology
Fibrinolysin - antagonists & inhibitors
Fibrinolysis - drug effects
Kinetics
Liver Neoplasms, Experimental - physiopathology
Plasminogen - metabolism
Rats
Urokinase-Type Plasminogen Activator - antagonists & inhibitors
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Summary:Dexamethasone induces an inhibitor of plasminogen-dependent fibrinolysis in rat hepatoma (HTC) cells. The specificity of the inhibitor for urokinase and plasmin was investigated using both fibrinolytic and esterolytic assays. Urokinase, but not plasmin, was inhibited by serum-free conditioned medium from cells incubated with 0.1 microM dexamethasone. The specificity of the inhibitor for plasminogen activator was demonstrated directly by the inhibition of the urokinase-catalyzed activation of 125I-plasminogen to 125I-plasmin. The inhibitory activity was stable to pH 3 for 2 h at 37 degrees C, a condition which inactivated fibrinolytic inhibitors in serum, suggesting a cellular origin for the inhibitor. Further evidence for the cellular origin was the constant daily production of inhibitor throughout a 4-day incubation with dexamethasone in serum-free medium. SF HTC-H1 cells, selected for their ability to grow in serum-free medium (Thompson, E. B., Anderson, C. U., and Lippman, M. E. (1975) J. Cell Physiol. 86, 403-412), were grown for 76 days (at least 30 generations) in the presence or absence of serum; dexamethasone induced equivalent amounts of inhibitory activity in cells which had been grown under both conditions. We conclude that the dexamethasone-induced inhibitor from HTC cells is a cellular product which is specific for the inhibition of plasminogen activation and which differs from other reported fibrinolytic inhibitors.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)34715-X