Receptor-mediated induction of human dermal fibroblast ectoaminopeptidase N by glucocorticoids.
Aminopeptidase N was demonstrated in human dermal fibroblasts as an ectoenzyme. The enzyme has wide substrate specificity, with a K(m) of 0.63 mM and Vmax of 338 nmol min-1 mg-1. Addition of fetal calf serum to the culture medium increased aminopeptidase N activity up to 63% by 10% serum in a 48-h culture. Treatment of fibroblasts by dexamethasone increased ectoaminopeptidase N activity in a dose- and time-dependent manner. Maximal increase of aminopeptidase N occurred after treatment with 1 microM dexamethasone for 3 days. Actinomycin D, a blocker of RNA synthesis, and cycloheximide, an inhibitor of protein synthesis, did not alter basal aminopeptidase N activity. However, they prevented stimulation by dexamethasone. RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone-induced increase in aminopeptidase N activity. This study shows that human dermal fibroblasts contain ectoaminopeptidase N controlled by glucocorticoids through a receptor-mediated mechanism.
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Nis, Yugoslavia.
V
V
Stefanović
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Vlahović
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M
Mitić-Zlatković
D018826:CD13 Antigens / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015735:Mifepristone / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*; D013379:Substrate Specificity; D015854:Up-Regulation / Q000502:physiology
D003470:Culture Media; D005938:Glucocorticoids; D011956:Receptors, Cell Surface; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; D015735:Mifepristone; D003907:Dexamethasone; D003513:Cycloheximide; D018826:CD13 Antigens