Circadian Regulation of Hepatic Cytochrome P450 2a5 by Peroxisome Proliferator-Activated Receptor γ

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Jiangming DengBaojian Wu

Abstract

Human CYP2A6 (Cyp2a5 in mice) plays an important role in metabolism and detoxification of various drugs and chemicals. Here, we investigated a potential role of peroxisome proliferator-activated receptor γ (Ppar-γ) in circadian regulation of the Cyp2a5 enzyme. We first showed that Cyp2a5 mRNA and protein in mouse liver displayed robust circadian oscillations. Consistent with a circadian protein pattern, Cyp2a5-mediated 7-hydroxylation of coumarin was circadian time-dependent. Formation of 7-hydroxycoumarin was more extensive at a dosing time of Zeitgeber time 2 (ZT2) than that at ZT14. Interestingly, the nuclear receptor Ppar-γ was also a circadian gene. Circadian Ppar-γ protein level was strongly correlated with the Cyp2a5 mRNA level (r = 0.989). Furthermore, Ppar-γ activation (by a selective agonist, rosiglitazone) upregulated Cyp2a5 expression in Hepa-1c1c7 cells, whereas Ppar-γ knockdown downregulated Cyp2a5 expression. Also, Ppar-γ knockdown blunted the rhythmicity of Cyp2a5 mRNA in serum-shocked Hepa-1c1c7 cells. In addition, a combination of promoter truncation analysis, mobility shift, and chromatin immunoprecipitation assays revealed that Ppar-γ directly bound to a PPAR response element (i.e., the -1418- to -1396-bp re...Continue Reading

References

Jan 9, 1998·Drug Metabolism Reviews·P Honkakoski, M Negishi
Jul 27, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·B G Lake
Apr 20, 2001·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J J BogaardsB Walther
Aug 29, 2002·Nature·Steven M Reppert, David R Weaver
Mar 1, 2005·Clinical Pharmacology and Therapeutics·Viba MalaiyandiRachel F Tyndale
Mar 9, 2005·Archives of Biochemistry and Biophysics·Dharamainder ChoudharyJohn B Schenkman
Apr 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Julie R JonesMark A Magnuson
Nov 16, 2007·Pharmacogenetics and Genomics·Takako TakiguchiShigehiro Ohdo
Dec 7, 2007·Chemical Research in Toxicology·F Peter Guengerich
Apr 5, 2008·Clinical Pharmacology and Therapeutics·S Muruganandan, C J Sinal
Jun 10, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Naoya MatsunagaShigehiro Ohdo
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Francis LéviJean Clairambault
Oct 12, 2010·PPAR Research·Maryam RakhshandehrooSander Kersten
Dec 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·I Hanukoglu
Apr 9, 2013·Journal of Lipid Research·Glenville JonesMartin Kaufmann
Aug 7, 2013·Trends in Cell Biology·Carrie L PartchJoseph S Takahashi
Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Robert DallmannFrédéric Gachon
Sep 23, 2014·Journal of Biological Rhythms·Jason P DeBruyneRobert Dallmann
Oct 23, 2014·Journal of Cellular Biochemistry·Weiwei LiuNanping Wang
Apr 14, 2016·Trends in Molecular Medicine·Robert DallmannFrancis Lévi
Dec 15, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tianpeng ZhangBaojian Wu

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Citations

Sep 24, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Mengjing ZhaoBaojian Wu
Mar 3, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Danyi LuBaojian Wu
Aug 14, 2019·British Journal of Pharmacology·Mengjing ZhaoBaojian Wu
Apr 3, 2020·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Mengjing ZhaoBaojian Wu
Dec 24, 2019·Acta Pharmaceutica Sinica. B·Yuhua LiHuichang Bi
Apr 2, 2021·The Journal of Pharmacy and Pharmacology·Lu GaoBaojian Wu
Jun 1, 2019·Chemico-biological Interactions·Yanke LinBaojian Wu

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