Regulation and induction of CYP3A11, CYP3A13 and CYP3A25 in C57BL/6J mouse liver

• Published in: Archives of biochemistry and biophysics Vol. 457; no. 1; pp. 105 - 110
• Main Authors: Down, M.J., Arkle, S., Mills, J.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2007
• Subjects: Age Factors; Animals; CAR; CYP3A11; CYP3A13; CYP3A25; Cytochrome P-450 CYP3A - biosynthesis; DEX; Dexamethasone - pharmacology; Enzyme Induction; Expression; Female; Glucocorticoids - pharmacology; Induction; Liver - drug effects; Liver - metabolism; Liver Extracts - metabolism; Male; Membrane Proteins - biosynthesis; Mice; Mice, Inbred C57BL; Mouse; PXR; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Steroid - biosynthesis; Retinoid X Receptor alpha - biosynthesis; RNA, Messenger - biosynthesis; RXRα; Sex Factors; Transcription Factors - biosynthesis; RXRα; Mouse; CAR; Expression; Induction; DEX; CYP3A11; CYP3A13; CYP3A25; PXR
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2006.09.017

This study reports that dexamethasone (DEX) significantly induces CYP3A11, CYP3A13 and CYP3A25 mRNA expression in male and female 4 days, 3 weeks and 18 weeks old C57BL/6J mice. Furthermore, CYP3A activity, as measured by erythromycin-
N-demethylation, is also significantly increased. PXR, RXRα and CAR are known to be involved in the induction of CYP3As. Here we report nuclear receptors PXR and RXRα but not CAR demonstrate gender- and age-dependent expression. Also, treatment of C57BL/6J mice with DEX induces PXR but not RXRα or CAR. In summary, we demonstrate DEX is not only able to up-regulate CYP3A expression and activity, but also the nuclear receptor PXR through which it may exert this effect. Furthermore, the gender- and age-dependent pattern of basal PXR and RXRα expression is similar to the 3 CYP3As analysed.