title: The effect of copper on the mRNA expression profile of xenobiotic-metabolizing enzymes in cultured rat H4-II-E cells.
abstract: Copper (Cu(2+)) is an essential element that plays important roles in physiological functions of the body. However, high Cu(2+) levels can have toxic implications. This study aims to investigate the constitutive response to Cu(2+) exposure of xenobiotic-metabolizing enzymes in cultured rat liver (H4-II-E) cell lines. Rat cells were exposed to copper sulfate (0-500 μM) for 24 h. The effects of Cu(2+) on the messenger RNA (mRNA) expressions of phase I and II enzymes and regulatory elements were examined using real-time PCR. Metallothionein mRNA expression was induced in a dose-dependent manner after treatment with Cu(2+). mRNA expressions of phase I enzymes such as cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2) were slightly induced after exposure to low concentrations of Cu(2+); however, CYP1A1 and CYP1A2 mRNA expressions were significantly downregulated at higher Cu(2+) concentrations. These effects corresponded with expression of aryl hydrocarbon receptor mRNA. The mRNA expressions of phase II enzymes were reduced upon exposure to Cu(2+). In conclusion, phase I and II enzyme expressions were significantly modulated upon Cu(2+) exposure. These results indicated that Cu(2+) exposure had toxicological implications for cultured H4-II-E cells.
authors.affiliation: Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Wageh Sobhy
authors.initials: WS
authors.lastname: Darwish
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Shouta
authors.initials: S
authors.lastname: Nakayama
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases; D019327:Copper Sulfate