Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in Five Mouse Genotypes with a Background of FVB

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2018 Apr 12

PMID 29637468

Citations 5

Authors

Jiamei M Chen

Qisong S Zhang

Xiaoyan Y Li

Xia Gong

Yanjiao J Ruan

Sijing J Zeng

Linlin L Lu

Xiaoxiao X Qi

Ying Wang

Ming Hu

Lijun J Zhu

Zhongqiu Q Liu

Affiliations

Soon will be listed here.

Abstract

Purpose: To systematically investigate tissue distribution and gender-specific protein expression of Cytochrome P450 (Cyps) in five mouse genotypes with a background of Friend virus B (FVB).

Methods: The Cyps were extracted from the tissue S9 fractions of the main metabolic organs and then absolutely quantified by applying the UHPLC-MS/MS method.

Results: The liver had the highest expression of Cyps, followed by the small intestine and kidney. In the liver, Cyp1a2, Cyp2c29, Cyp2c39, Cyp2d22, Cyp2e1, and Cyp3a11 were the main isoforms. Cyp1a2 and Cyp2c29 were male-specific, while Cyp2c39 was female-specific. Compared with the expression in Wild-type (WT) FVB mice, the expression of Cyp1a2, Cyp1b1, Cyp2d22, and Cyp3a25 significantly decreased in female efflux transporter (ET) knockout mice. In the small intestine, Cyp2c29 and Cyp3a11 were the major isoforms. Knockout of ET didn't alter the expression levels of most Cyps. However, female ET knockout mice presented higher Cyp2c29 expression than WT FVB mice. The Cyp7a1 expression was markedly decreased in ET knockout mice except Bcrp1 mice. In the kidney, Cyp2e1 was the main isoform and exhibited male specificity. Knockout of ET slightly affected the protein expression of Cyps in the brain, heart, lung, spleen and stomach.

Conclusions: A comprehensive understanding of the distribution characteristics and gender-specific expression of Cyps in major metabolic organs of WT and ET knockout FVB mice should contribute to a better understanding of drug efficacy and toxicity, and drug-drug interactions.

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References

Tsunedomi R, Hazama S, Okayama N, Oka M, Nagano H . Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray. Cancer Sci. 2017; 108(7):1504-1509. PMC: 5497725. DOI: 10.1111/cas.13272. View

Agarwal S, Uchida Y, Mittapalli R, Sane R, Terasaki T, Elmquist W . Quantitative proteomics of transporter expression in brain capillary endothelial cells isolated from P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp/Bcrp knockout mice. Drug Metab Dispos. 2012; 40(6):1164-9. PMC: 3362790. DOI: 10.1124/dmd.112.044719. View

Klein K, Winter S, Turpeinen M, Schwab M, Zanger U . Pathway-Targeted Pharmacogenomics of CYP1A2 in Human Liver. Front Pharmacol. 2011; 1:129. PMC: 3171976. DOI: 10.3389/fphar.2010.00129. View

Seibert C, Davidson B, Fuller B, Patterson L, Griffiths W, Wang Y . Multiple-approaches to the identification and quantification of cytochromes P450 in human liver tissue by mass spectrometry. J Proteome Res. 2009; 8(4):1672-81. PMC: 2939981. DOI: 10.1021/pr800795r. View

Paine M, Hart H, Ludington S, Haining R, Rettie A, Zeldin D . The human intestinal cytochrome P450 "pie". Drug Metab Dispos. 2006; 34(5):880-6. PMC: 2222892. DOI: 10.1124/dmd.105.008672. View

Meibohm B, Beierle I, Derendorf H . How important are gender differences in pharmacokinetics?. Clin Pharmacokinet. 2002; 41(5):329-42. DOI: 10.2165/00003088-200241050-00002. View

Agarwal S, Sane R, Gallardo J, Ohlfest J, Elmquist W . Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux. J Pharmacol Exp Ther. 2010; 334(1):147-55. PMC: 2912048. DOI: 10.1124/jpet.110.167601. View

Diani-Moore S, Papachristou F, Labitzke E, Rifkind A . Induction of CYP1A and cyp2-mediated arachidonic acid epoxygenation and suppression of 20-hydroxyeicosatetraenoic acid by imidazole derivatives including the aromatase inhibitor vorozole. Drug Metab Dispos. 2006; 34(8):1376-85. DOI: 10.1124/dmd.106.009498. View

Wolbold R, Klein K, Burk O, Nussler A, Neuhaus P, Eichelbaum M . Sex is a major determinant of CYP3A4 expression in human liver. Hepatology. 2003; 38(4):978-88. DOI: 10.1053/jhep.2003.50393. View

10.

Kim H, Reddy S, Novak R . 3-Methylcholanthrene and pyridine effects on CYP1A1 and CYP1A2 expression in rat renal tissue. Drug Metab Dispos. 1995; 23(8):818-24. View

11.

Chen J, Zheng H, Zeng S, Xie C, Li X, Yan T . Profiles and Gender-Specifics of UDP-Glucuronosyltransferases and Sulfotransferases Expressions in the Major Metabolic Organs of Wild-Type and Efflux Transporter Knockout FVB Mice. Mol Pharm. 2017; 14(9):2967-2976. DOI: 10.1021/acs.molpharmaceut.7b00435. View

12.

Uno Y, Hosaka S, Yamazaki H . Identification and analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in cynomolgus macaques. J Vet Med Sci. 2015; 76(12):1647-50. PMC: 4300383. DOI: 10.1292/jvms.14-0313. View

13.

Diliberto J, Akubue P, Luebke R, Birnbaum L . Dose-response relationships of tissue distribution and induction of CYP1A1 and CYP1A2 enzymatic activities following acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Toxicol Appl Pharmacol. 1995; 130(2):197-208. DOI: 10.1006/taap.1995.1025. View

14.

Ding X, Kaminsky L . Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol. 2002; 43:149-73. DOI: 10.1146/annurev.pharmtox.43.100901.140251. View

15.

Lofgren S, Baldwin R, Carleros M, Terelius Y, Fransson-Steen R, Mwinyi J . Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone. Drug Metab Dispos. 2009; 37(7):1505-12. PMC: 2698944. DOI: 10.1124/dmd.109.026963. View

16.

Joshi M, Tyndale R . Regional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine. Neuropharmacology. 2005; 50(5):568-75. DOI: 10.1016/j.neuropharm.2005.11.001. View

17.

Williams J, Hyland R, Jones B, Smith D, Hurst S, Goosen T . Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004; 32(11):1201-8. DOI: 10.1124/dmd.104.000794. View

18.

Erickson S, Lear S, Deane S, Dubrac S, Huling S, Nguyen L . Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice. J Lipid Res. 2003; 44(5):1001-9. DOI: 10.1194/jlr.M200489-JLR200. View

19.

Jarukamjorn K, Sakuma T, Jaruchotikamol A, Ishino Y, Oguro M, Nemoto N . Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver. Toxicology. 2005; 219(1-3):97-105. DOI: 10.1016/j.tox.2005.11.014. View

20.

Kumagai Y, Sekimoto M, Okamoto M, Kurita R, Kojima M, Degawa M . Involvement of hepatic IL-1 in the strain-dependent sex differences in serum total cholesterol levels in rats. Biol Pharm Bull. 2014; 37(4):654-8. DOI: 10.1248/bpb.b13-00982. View