Suppression of plasminogen activator activity by dexamethasone in cultured cardiac myocytes.
Cardiac rat myocytes in primary culture exhibit a membrane-bound and a secreted form of plasminogen activator (PA). Growth of the cells in presence of 2 X 10(-8) M or 10(-7) M dexamethasone markedly reduced both the membrane-bound and the secreted activities of PA. The extent of reduction depended on the time of addition as well as on the length of exposure to the hormone. A similar concentration of estradiol had no effect on PA activity of the myocytes. Cardiac rat fibroblasts in primary culture showed only the particulate form of the enzyme. Exposure of the fibroblasts to 10(-7) M dexamethasone produced a marked inhibition of this activity. The inhibition of PA activity in medium conditioned by dexamethasone-treated myocytes could be relieved by treatment of the medium with 1% (v/v) sodium dodecyl sulphate (SDS). Digestion with 3.3 micrograms/ml bovine trypsin caused an increase in PA activity of media conditioned with control or dexamethasone-treated cells. The present results indicate that cardiac myocytes and fibroblasts produce PA, and that the modulation of PA by glucocorticoid either involves formation of an inactive PA-protein complex or production of an inactive proenzyme. Since glucocorticoids are often administered in conjunction with fibrinolytic enzymes to re-establish cardial perfusion after thrombosis, the present findings indicate further research to assess potential clinical effects of glucocorticoids through suppression of endogenous PA activity in the heart.
D000818:Animals; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009206:Myocardium / Q000378:metabolism*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015849:Plasminogen Inactivators; D051381:Rats; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D015849:Plasminogen Inactivators; D004958:Estradiol; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator