Induction and regulation of CYP2E1 in murine liver after acute and chronic acetone administration.
The effects of acute and chronic acetone administration on hepatic Cyp2e1 were investigated in mice. Acute treatment consisted of a single dose of acetone (5 ml/kg) given intragastrically, whereas the chronic regimen consisted of 1% acetone in drinking water for 8 days. We examined 1) relative induction of Cyp2e1 protein by immunoblotting, 2) relative induction of enzyme catalytic activity (p-nitrophenol hydroxylation), and 3) Cyp2e1 mRNA levels associated with acute and chronic treatment regimens. Western immunoblotting, using a monoclonal antibody (Mab 1-98-1) specific for rat ethanol-inducible P-450, detected a band of M(r) 51,000 in liver microsomes of both control and acetone-treated mice. Densitometric quantitation showed significant enhancement of the intensity of this band by 4.4- and 5.3-fold after acute and chronic acetone treatments, respectively. Hydroxylation of p-nitrophenol was increased 2.3-fold in microsomes from livers exposed acutely to acetone, as compared with an increase of 3.7-fold in microsomes from livers exposed chronically. The induction of Cyp2e1 protein, as well as of catalytic activity, by acetone was not accompanied by significant alterations in the levels of Cyp2e1 mRNA. These results demonstrate a difference in induced increases of Cyp2e1 between acute and chronic acetone treatments: significantly higher induction of both protein and catalytic activity is induced by treatment under chronic vs. acute conditions.
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.
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Forkert
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Redza
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Mangos
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Park
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D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015152:Blotting, Northern; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D015342:DNA Probes; D004790:Enzyme Induction / Q000187:drug effects; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009596:Nitrophenols / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D009596:Nitrophenols; D012333:RNA, Messenger; D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C024836:4-nitrophenol