Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells.
The interactions of CYP11B1 (cytochrome P-45011beta), CYP11B2 (cytochrome P-450aldo) and CYP11A1 (cytochrome P-450scc) were investigated by cotransfection of their cDNA into COS-1 cells. The effect of CYP11A1 on CYP11B isozymes was examined by studying the conversion of 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone and aldosterone. It was shown that when human or bovine CYP11B1 and CYP11A1 were cotransfected they competed for the reducing equivalents from the limiting source contained in COS-1 cells; this resulted in a decrease of the CYP11B activities without changes in the product formation patterns. The competition of human CYP11A1 with human CYP11B1 and CYP11B2 could be diminished with excess expression of bovine adrenodoxin. However, the coexpression of bovine CYP11B1 and CYP11A1 in the presence of adrenodoxin resulted in a stimulation of 11beta-hydroxylation activity of CYP11B1 and in a decrease of the 18-hydroxycorticosterone and aldosterone formation. These results suggest that the interactions of CYP11A1 with CYP11B1 and CYP11B2 do not have an identical regulatory function in human and in bovine adrenal tissue.
Cao
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PR
Universität des Saarlandes, Fachrichtung 12.4-Biochemie, Saarbrücken, Germany.
Bernhardt
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R
D000325:Adrenodoxin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D019556:COS Cells / Q000201:enzymology*; D002417:Cattle; D002522:Chlorocebus aethiops; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology
D007527:Isoenzymes; D000325:Adrenodoxin; D000450:Aldosterone; D006899:Mixed Function Oxygenases; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme