Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: association with an attenuated CYP2B induction by phenobarbital.
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.
Numazawa
Satoshi
S
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. numazawa@pharm.showa-u.ac.jp
Shindo
Sawako
S
Maruyama
Keiji
K
Chibana
Fumika
F
Kawahara
Yosuke
Y
Ashino
Takashi
T
Tanaka
Sachiko
S
Yoshida
Takemi
T
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D000090702:Constitutive Androstane Receptor; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital