PP  Vol.4 No.2 , April 2013
Diurnal Variation of Nuclear Receptors in Mice with or without Fasting
Abstract: Nuclear receptors such as pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate the transcription of transporter and cytochrome P450 (CYP). The diurnal variation was observed in some transporters regulated by nuclear receptors. We investigated whether diurnal variation in PXR and CAR exists in mice. We also examined the effect of food intake on the diurnal rhythm of hepatic PXR and CAR using fed and fasted mice. In liver and small intestine of fed mice, the mRNA levels of PXR and CAR were unchanged between 7:00 AM and 7:00 PM. In contrast to fed mice, fasting mice partly exhibited the diurnal variation in PXR, not in CAR. The mRNA levels of PXR at 7:00 AM were significantly higher than that those at 7:00 PM in liver of fasting mice. These results indicated the different effects of fasting in mice on diurnal variation of PXR in each tissue.
Cite this paper: A. Kawase, T. Ohgami, I. Yoshida, Y. Tsunokuni and M. Iwaki, "Diurnal Variation of Nuclear Receptors in Mice with or without Fasting," Pharmacology & Pharmacy, Vol. 4 No. 2, 2013, pp. 240-243. doi: 10.4236/pp.2013.42033.

[1]   S. A. Kliewer, J. T. Moore, L. Wade, J. L. Staudinger, M. A. Watson, S. A. Jones, D. D. McKee, B. B. Oliver, T. M. Willson, R. H. Zetterstrom, T. Perlmann and J. M. Lehmann, “An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway,” Cell, Vol. 92, No. 1, 1998, pp. 73-82. doi:10.1016/S0092-8674(00)80900-9

[2]   P. Honkakoski, I. Zelko, T. Sueyoshi and M. Negishi, “The Nuclear Orphan Receptor CAR-Retinoid X Receptor Heterodimer Activates the Phenobarbital-Responsive Enhancer Module of the CYP2B Gene,” Molecular and Cellular Biology, Vol. 18, 1998, pp. 5652-5658.

[3]   D. J. Waxman, “P450 Gene Induction by Structurally Diverse Xenochemicals: Central Role of Nuclear Receptors CAR, PXR, and PPAR,” Archives of Biochemistry and Biophysics, Vol. 369, No. 1, 1999, pp. 11-23. doi:10.1006/abbi.1999.1351

[4]   X. Pan, T. Terada, M. Okuda and K. Inui, “Altered Diurnal Rhythm of Intestinal Peptide Transporter by Fasting and Its Effects on the Pharmacokinetics of Ceftibuten,” Journal of Pharmacology and Experimental Therapeutics, Vol. 307, No. 2, 2003, pp. 626-632. doi:10.1124/jpet.103.055939

[5]   H. Ando, H. Yanagihara, K. Sugimoto, Y. Hayashi, S. Tsuruoka, T. Takamura, S. Kaneko and A. Fujimura, “Daily Rhythms of P-Glycoprotein Expression in Mice,” Chronobiology International, Vol. 22, No. 4, 2005, pp. 655-665. doi:10.1080/07420520500180231

[6]   C. S. Chaurasia, M. A. Alterman, P. Lu and R. P. Hanzlik, “Biochemical Characterization of Lauric Acid OmegaHydroxylation by a CYP4A1/NADPH-Cytochrome P450 Reductase Fusion Protein,” Archives of Biochemistry and Biophysics, Vol. 317, No. 1, 1995, pp. 161-169. doi:10.1006/abbi.1995.1149

[7]   J. Y. Hong, J. M. Pan, F. J. Gonzalez, H. V. Gelboin and C. S. Yang, “The Induction of a Specific Form of Cytochrome P-450 (P-450j) by Fasting,” Biochemical and Biophysical Research Communications, Vol. 142, No. 3, 1987, pp. 1077-1083. doi:10.1016/0006-291X(87)91525-7

[8]   S. Imaoka, Y. Terano and Y. Funae, “Changes in the Amount of Cytochrome P450s in Rat Hepatic Microsomes with Starvation,” Archives of Biochemistry and Biophysics, Vol. 278, No. 1, 1990, pp. 168-178. doi:10.1016/0003-9861(90)90245-T

[9]   Q. Ma, G. A. Dannan, F. P. Guengerich and C. S. Yang, “Similarities and Differences in the Regulation of Hepatic Cytochrome P-450 Enzymes by Diabetes and Fasting in Male Rats,” Biochemical Pharmacology, Vol. 38, No. 19, 1989, pp. 3179-3184. doi:10.1016/0006-2952(89)90611-4

[10]   A. Kawase, Y. Tsunokuni and M. Iwaki, “Effects of Alterations in CAR on Bilirubin Detoxification in Mouse Collagen-Induced Arthritis,” Drug Metabolism and Disposition, Vol. 35, No. 2, 2007, pp. 256-261. doi:10.1124/dmd.106.011536

[11]   A. Kawase, I. Yoshida, Y. Tsunokuni and M. Iwaki, “Decreased PXR and CAR Inhibit Transporter and CYP mRNA Levels in the Liver and Intestine of Mice with Collagen-Induced Arthritis,” Xenobiotica, Vol. 37, No. 4, 2007, pp. 366-374. doi:10.1080/00498250701230534

[12]   J. M. Maglich, C. M. Stoltz, B. Goodwin, D. HawkinsBrown, J. T. Moore and S. A. Kliewer, “Nuclear Pregnane X Receptor and Constitutive Androstane Receptor Regulate Overlapping but Distinct Sets of Genes Involved in Xenobiotic Detoxification,” Molecular Pharmacology, Vol. 62, No. 3, 2002, pp. 638-646. doi:10.1124/mol.62.3.638