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CAR/PXR provide directives for Cyp3a41 gene regulation differently from Cyp3a11

The Pharmacogenomics Journal volume 4, pages 91–101 (2004)Cite this article

ABSTRACT

This study reports that Cyp3a41 gene contains 13 exons and is localized on the chromosome 5. CYP3A41 is a female-specific isoform that is predominantly expressed in the liver. Estrogen signaling is not responsible for its female specificity. CYP3A41 expression in kidney and brain is observed only in 50% of mice examined. PXR mediates dexamethasone-dependent suppression of CYP3A41. In contrast to CYP3A11, CYP3A41 expression is not induced by pregnenolone-16α-carbonitrile (PCN) in wild-type mice, but is significantly suppressed by PCN in PXR−/− mice. Phenobarbital and TCPOBOP induce CYP3A11 expression only in the presence of CAR, but have no effect on CYP3A41 expression. Immunoblot and erythromycin demethylase activity analysis reveal robust CYP3A induction after PCN treatment, which is poorly correlated to CYP3A41. These findings suggest a differential role for CAR/PXR in regulating individual CYP3A isoforms by previously characterized CYP3A inducers.

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Abbreviations

CAAT:

CAAT-binding factor

CAR:

constitutive androstane receptor

CYP:

cytochrome P450

GATA1:

GATA-binding factor 1

GR:

glucocorticoid receptor

HNF:

hepatocyte nuclear factor

OCT1:

octamer-binding factor 1

PBREM:

phenobarbital response element

PXR:

pregnane X receptor

RT-PCR:

reverse transcription-polymerase chain reaction

SP1:

stimulating factor 1

STAT:

signal transducer and activator of transcription

TCPOBOP:

1,4 bis{2-(3,5 dichloropyridyloxy)} benzene

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Acknowledgements

We would like to thank Ms Cheri M Turman for careful reading of the manuscript.

Author information

Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, The University of Texas Medical School of Houston, TX, USA

    S Anakk, A Kalsotra, Y Kikuta & H W Strobel

  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    W Huang, J Zhang & D D Moore

  3. Department of Pharmacology & Toxicology University of Kansas Medical Center, Lawrence, KS, USA

    J L Staudinger

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  1. S Anakk
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  2. A Kalsotra
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Correspondence to H W Strobel.

Additional information

The data presented here form part of the dissertation of Sayeepriyadarshini Anakk submitted to the faculty of the University of Texas Houston, Graduate School of Biomedical Sciences, in partial fulfillment of the requirements for the Doctor in Philosophy degree.

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Anakk, S., Kalsotra, A., Kikuta, Y. et al. CAR/PXR provide directives for Cyp3a41 gene regulation differently from Cyp3a11. Pharmacogenomics J 4, 91–101 (2004). https://doi.org/10.1038/sj.tpj.6500222

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