Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures.
Administration of ethanol, dimethylsulphoxide, 2-propanol or imidazole to rats caused 2-7-fold increases in the level of hepatic ethanol-inducible cytochrome P-450 (P-450j), without any concomitant enhancement of corresponding mRNA. All the compounds were able to stabilize P-450j in hepatocyte cultures for at least three days, whereas P-450j mRNA rapidly disappeared from the cultures. A correlation was reached between the concentration of Me2SO, ethanol and 2-propanol necessary to maintain P-450j in the cell cultures and their binding affinities to the enzyme. It is suggested that the ligand-bound form of P-450j in the hepatocytes is protected from degradation.
Eliasson
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Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
Johansson
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Ingelman-Sundberg
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M
D000433:1-Propanol / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D007093:Imidazoles; D012333:RNA, Messenger; D000431:Ethanol; C029899:imidazole; D003577:Cytochrome P-450 Enzyme System; D000433:1-Propanol; D004121:Dimethyl Sulfoxide