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Regulation of Xenobiotic Detoxification by PXR, CAR, GR, VDR and SHP Receptors: Consequences in Physiology

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Transcription Factors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 166))

Abstract

Cytochromes P450 (CYP) from families CYP1/2/3 are involved in xenobiotic detoxification and are regulated by numerous agents including xenobiotics, plant and fungal toxins, bile salts, etc. Nuclear receptors PXR (pregnane X receptor, NR1I3) and CAR (constitutive androstane receptor, NR1I2) control the expression of distinct but overlapping arrays of genes including the CYP2/3 families. These receptors are involved in a tangle of regulatory networks including those pathways controlling vitamin D and cholesterol/bile salt homeostasis. They are expressed under the control of the glucocorticoid receptor and are inhibited by the short heterodimer partner (SHP). The crosstalk between both PXR and CAR and other nuclear receptors allows for the establishing and prediction of functional interferences between the detoxification and other signaling and metabolic pathways. These interferences provide new clues for the interpretation of xenobiotic adverse effects, such as bone demineralization, and for understanding how physiopathological factors, such as biliary salts or inflammation and infections, affect an organism’s ability to detoxify xenobiotics.

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  1. UMR632, 1919Route de Mende, 34293, Montpellier Cedex 5, France

    J. M. Pascussi, Z. Dvorák, E. Assenat, L. Drocourt, P. Maurel & M. J. Vilarem

  2. FRE2593, CRBM-CNRS, Montpellier, France

    S. Gerbal-Chaloin

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  1. J. M. Pascussi
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  2. Z. Dvorák
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  3. S. Gerbal-Chaloin
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  4. E. Assenat
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  1. Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Manfred Gossen

  2. atugen AG, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Jörg Kaufmann

  3. Department of Biochemistry and Molecular Biology, Michigan State University, 510 Biochemistry Building, East Lansing, MI, 48824-1319, USA

    Steven J. Triezenberg (Associate Director) (Associate Director)

  4. Graduate Program in Cell and Molecular Biology, Michigan State University, 510 Biochemistry Building, East Lansing, MI, 48824-1319, USA

    Steven J. Triezenberg (Associate Director) (Associate Director)

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Pascussi, J.M. et al. (2004). Regulation of Xenobiotic Detoxification by PXR, CAR, GR, VDR and SHP Receptors: Consequences in Physiology. In: Gossen, M., Kaufmann, J., Triezenberg, S.J. (eds) Transcription Factors. Handbook of Experimental Pharmacology, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18932-6_13

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  • DOI: https://doi.org/10.1007/978-3-642-18932-6_13

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