Pharmaceutical Research

, 35:114 | Cite as

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

  • 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
Research Paper
  • 39 Downloads

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.

Key words

cytochrome P450 efflux transporter gender-specific knockout tissue distribution 

Abbreviations

CYP

Cytochrome P450

ET

Efflux transporter

FVB

Friend virus B

WT

Wild-type

Notes

Author Contributions

Participated in research design: Chen, Hu, and Liu.

Conducted experiments: Chen, Li, and Zeng.

Contributed new reagents or analytic tools: Gong, Ruan, Lu, Qi, Wang, and Hu.

Performed data analysis: Chen, Zhang, Zhu, and Liu.

Wrote or contributed to the writing of the manuscript: Chen, Zhang, Zhu, Hu, and Liu.

Supplementary material

11095_2018_2389_MOESM1_ESM.docx (31 kb)
ESM 1 (DOCX 31 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jiamei M. Chen
    • 1
  • Qisong S. Zhang
    • 1
  • Xiaoyan Y. Li
    • 1
  • Xia Gong
    • 1
  • Yanjiao J. Ruan
    • 1
  • Sijing J. Zeng
    • 1
  • Linlin L. Lu
    • 1
  • Xiaoxiao X. Qi
    • 1
  • Ying Wang
    • 1
  • Ming Hu
    • 2
  • Lijun J. Zhu
    • 1
  • Zhongqiu Q. Liu
    • 1
    • 3
  1. 1.International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouPeople’s Republic of China
  2. 2.Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy,University of HoustonHoustonUSA
  3. 3.State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and TechnologyMacauChina

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