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

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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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Abbreviations

CYP:

Cytochrome P450

ET:

Efflux transporter

FVB:

Friend virus B

WT:

Wild-type

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Author information

Authors and Affiliations

  1. International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China

    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, Lijun J. Zhu & Zhongqiu Q. Liu

  2. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy,, University of Houston, Houston, Texas, 77030, USA

    Ming Hu

  3. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, SAR, China

    Zhongqiu Q. Liu

Authors
  1. Jiamei M. Chen
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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.

Corresponding authors

Correspondence to Lijun J. Zhu or Zhongqiu Q. Liu.

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Chen, J.M., Zhang, Q.S., Li, X.Y. et al. Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in five Mouse Genotypes with a Background of FVB. Pharm Res 35, 114 (2018). https://doi.org/10.1007/s11095-018-2389-2

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  • DOI: https://doi.org/10.1007/s11095-018-2389-2

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