Modulation of steroid hydroxylase activity in stably transfected V79MZh11B1 and V79MZh11B2 cells by PKC and PKD inhibitors.
We recently observed that treatment of CYP11B2-expressing COS-1 cells with the broad range kinase inhibitor, staurosporine (STS), strongly inhibited aldosterone biosynthesis, indicating that the activity of a kinase might be a prerequisite for steroid hydroxylase activity. In an attempt to identify such kinases, we measured conversion of 11-deoxycortisol (RSS) and 11-deoxycorticosterone (DOC) by V79MZh11B1 and V79MZh11B2 cells, respectively, in the presence of STS and also after treatment with the kinase inhibitors chelerythrine, rottlerin and Gö 6976. The conversion of both substrates by both cell lines was affected in a selective manner by the kinase inhibitors, suggesting that the activity of the novel PKC-delta and either of conventional PKCs or of PKD alter steroid hydroxylation activity, with their influence depending on both the cytochrome P450 tested and on its steroid substrate.
Bureik
Matthias
M
Universität des Saarlandes, FR 8.8 Biochemie, Postfach 151150, D-66041 Saarbrücken, Germany.
Zeeh
Annette
A
Bernhardt
Rita
R
D000098:Acetophenones / Q000494:pharmacology; D000470:Alkaloids; D053119:Benzophenanthridines; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D003350:Cortodoxone / Q000378:metabolism; D003900:Desoxycorticosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006900:Hydroxylation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014162:Transfection
D000098:Acetophenones; D000470:Alkaloids; D053119:Benzophenanthridines; D001578:Benzopyrans; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010617:Phenanthridines; C081021:Go 6976; D003900:Desoxycorticosterone; C085746:rottlerin; C016299:chelerythrine; D013250:Steroid Hydroxylases; C089212:protein kinase D; D011493:Protein Kinase C; D019311:Staurosporine; D003350:Cortodoxone