Comparison of cytochrome P450 isoenzyme profiles in rat liver and hepatocyte cultures. The effects of model inducers on apoproteins and biotransformation activities.
作者： H.M. Wortelboer , C.A. de Kruif , A.A.J. van Iersel , H.E. Falke , J. Noordhoek
DOI: 10.1016/0006-2952(91)90726-L
关键词: Hepatocyte 、 Cell culture 、 In vivo 、 Hydroxylation 、 Cytochrome P450 、 Endocrinology 、 Biology 、 Internal medicine 、 In vitro 、 Clofibric acid 、 Phenobarbital
摘要: Abstract The metabolic profile of seven subfamilies cytochrome P450 (P450IA, IIA, IIB, IIC, IIE, IIIA, IVA) was studied in rat liver (in vivo) and primary hepatocyte cultures vitro) after treatment with various inducers. dealkylation 7-ethoxyresorufin (EROD) 7-pentoxyresorufin (PROD), aniline 4-hydroxylation the regio- stereoselective hydroxylation testosterone were measured to characterize isoenzyme pattern intact hepatocytes microsomes. Occurrence apoproteins determined using Western blotting. Primary retain capacity respond inducers isoenzymes belonging six different IIIA IVA). Treatment cells β-naphthoflavone revealed a P450-activity similar vivo, namely highly induced EROD (P450IA1), small enhancement 7α-hydroxylation (P450IIA) marked reduction 2α- 16α-hydroxylation (P450IIC11). Exposure cultured phenobarbital resulted higher 16β-hydroxylation (reflecting P450IIB), though lesser extent than vivo. induction P450IIIA due both dexamethasone, as mirrored by 6β- 15β-hydroxylation testosterone, same clofibric acid an one observed microsomes from clofibrate-treated rats: apoprotein P450IVA well P450IIB1/2 its associated activities (PROD 16β-hydroxylation) induced. Isoniazid, known vivo inducer P450IIE1 4-hydroxylation, did not change any P450-dependent vitro.
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