Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: association with an attenuated CYP2B induction by phenobarbital |
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Authors: | Numazawa Satoshi Shindo Sawako Maruyama Keiji Chibana Fumika Kawahara Yosuke Ashino Takashi Tanaka Sachiko Yoshida Takemi |
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Institution: | Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan |
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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. |
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Keywords: | 2-AAF 2-acetylaminofluorene CAR constitutive androstane receptor CCRP cytosolic CAR retention protein CYP cytochrome P450 GAPDH glyceraldehyde-3-phosphate dehydrogenase GFP green fluorescent protein GSTp placenta form of glutathione S-transferase PB phenobarbital PBREM PB-responsive enhancer module PROD 7-pentoxyresorufin-O-dealkylase RXR retinoid X receptor TCPOBOP 1 4-bis[2-(3 5-dichloropyridyloxy)]benzene |
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