Corticosterone 6 beta-hydroxylase in A6 epithelia: a steroid-inducible cytochrome P-450
| Autor: | V. M. Phillips, W. M. Grogan, Charles O. Watlington, Philip S. Guzelian, Erin G. Schuetz |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
Hydrocortisone Physiology Metabolite Kidney Dexamethasone Cell Line chemistry.chemical_compound Cytochrome P-450 Enzyme System Corticosterone Microsomes Internal medicine medicine Animals Troleandomycin Enzyme inducer Aldosterone chemistry.chemical_classification biology Cytochrome P450 Cell Biology Enzyme assay Kinetics Enzyme Endocrinology chemistry Enzyme Induction Steroid Hydroxylases biology.protein Steroids Software medicine.drug |
| Zdroj: | American Journal of Physiology-Cell Physiology. 258:C480-C488 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1990.258.3.c480 |
| Popis: | We found microsomal corticosterone 6 beta-hydroxylase (6 beta-OHase) from cultured A6 kidney epithelial cells to be a cytochrome P-450 enzyme with both similarities to and differences from the rat liver steroid 6 beta-OHase P-450p. Enzyme activity was inhibited by CO, alpha-naphthoflavone, metyrapone, and clotrimazole, well-known inhibitors of P-450 enzymes, and increased by known inducers of P-450 enzymes, including dilantin, phenobarbital sodium, and corticosteroids. Moreover, some additional, relatively specific inducers of P-450p (troleandomycin and pregnenolone-16 alpha-carbonitrile) also induced the A6 6 beta-OHase, whereas inducers of other forms of P-450 (aroclor, spironolactone, and isosafrole) appeared to repress the A6 enzyme. The time course of increase in enzyme activity and increased cellular cytochrome P-450 content were consistent with increased levels of enzyme protein. Induction of 6 beta-OHase by the substrate (corticosterone), the metabolite (6 beta-OH-corticosterone), dexamethasone, and aldosterone was biphasic as a function of inducer concentration, with approximate 50% effective concentration (EC50) values of 10(-8)-10(-9) M and 10(-5)-10(-6) M for the respective components of induction. Cortisol also induced the enzyme at 10(-8)-10(-6) M; however, its metabolite 6 beta-OH-cortisol was ineffective or decreased activity at higher concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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