Abstract
Phenobarbital (PB) induction of CYP2B, a representative target gene of constitutive androstane receptor (CAR), has been observed to be attenuated in preneoplastic lesions of rat liver; however, molecular basis for this attenuation is poorly understood. In this report, we provide evidence indicating that the CAR expressed in the hepatic preneoplastic lesions of rats and mice was resistant to nuclear translocation and transactivation of the PB-responsive enhancer module upon PB treatment. These observations suggest that the attenuation of the induction of CYP2B by PB in hepatic preneoplastic lesions is evidently a consequence of impaired nuclear translocation of CAR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Animals
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Cell Nucleus / chemistry
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Cell Nucleus / metabolism*
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Constitutive Androstane Receptor
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Cytochrome P-450 CYP2B1 / genetics
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Cytochrome P-450 CYP2B1 / metabolism*
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Down-Regulation
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Liver / drug effects*
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Liver / pathology
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Liver Neoplasms / metabolism*
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Male
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Mice
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Phenobarbital / pharmacology*
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Precancerous Conditions / metabolism*
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Rats
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Receptors, Cytoplasmic and Nuclear / analysis
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation / drug effects
Substances
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Constitutive Androstane Receptor
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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Cytochrome P-450 CYP2B1
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Phenobarbital