The effect of copper on the mRNA expression profile of xenobiotic-metabolizing enzymes in cultured rat H4-II-E cells

Abstract

Copper (Cu2+) is an essential element that plays important roles in physiological functions of the body. However, high Cu2+ levels can have toxic implications. This study aims to investigate the constitutive response to Cu2+ exposure of xenobiotic-metabolizing enzymes in cultured rat liver (H4-II-E) cell lines. Rat cells were exposed to copper sulfate (0-500 mu M) for 24 h. The effects of Cu2+ 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 Cu2+. 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 Cu2+; however, CYP1A1 and CYP1A2 mRNA expressions were significantly downregulated at higher Cu2+ concentrations. These effects corresponded with expression of aryl hydrocarbon receptor mRNA. The mRNA expressions of phase II enzymes were reduced upon exposure to Cu2+. In conclusion, phase I and II enzyme expressions were significantly modulated upon Cu2+ exposure. These results indicated that Cu2+ exposure had toxicological implications for cultured H4-II-E cells