title: Species-specific responses of constitutively active receptor (CAR)-CYP2B coupling: lack of CYP2B inducer-responsive nuclear translocation of CAR in marine teleost, scup (Stenotomus chrysops).
abstract: The mammalian constitutively active receptor (CAR) is a novel ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to pharmaceutical agents (phenobarbital) and halogenated aromatic hydrocarbons (ortho-substituted PCBs). The occurrence and physiological function of this protein are as yet unknown in marine animals, where there has been a paradoxical lack of induction by PB-type chemicals. One approach to understanding CAR function is to study the evolutionary history of processes such as CAR-CYP2B coupling. In this study, CAR function was evaluated in a representative teleost fish (scup, Stenotomus chrysops). Treatment of scup with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is one of the most potent CYP2B inducers in mouse, caused no increase in hepatic alkoxyresorufin O-dealkylase activity nor in immunodetectable CYP2B-like protein levels. Western blot analyses of scup livers using anti-human CAR antisera revealed the occurrence of a putative CAR homologue in nuclear and cytoplasmic fractions, but no nuclear accumulation of CAR following TCPOBOP treatment, which is a first step regulating the transcriptional activation of CYP2B genes in mouse. Immunohistochemical study also showed no translocation of CAR into nucleus in the hepatocytes of TCPOBOP-treated scup. These results suggest that there may be species-specific differences in CAR activation or CAR-CYP2B coupling signaling transduction in fish from those in mouse.
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA. iwatah@agr.ehime-u.ac.jp
authors.forename: Hisato
authors.initials: H
authors.lastname: Iwata
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yoshinari
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
authors.forename: John J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D000090702:Constitutive Androstane Receptor; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism* / Q000502:physiology; D005399:Fishes / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism* / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital