Science Links Japan | CYP2B Gene Structures and Induction Mechanism: Comparative Studies Using Guinea Pigs with Low Inducibility and Mutant Rats That Lack Responce to Phenobarbital-mediated Induction.

CYP2B Gene Structures and Induction Mechanism: Comparative Studies Using Guinea Pigs with Low Inducibility and Mutant Rats That Lack Responce to Phenobarbital-mediated Induction.

Accession number;00A0997669

Title;CYP2B Gene Structures and Induction Mechanism: Comparative Studies Using Guinea Pigs with Low Inducibility and Mutant Rats That Lack Responce to Phenobarbital-mediated Induction.

Author; YAMAMOTO MIDORI (Kyushu Univ., Grad. Sch.) MATSUMOTO SANAE (Kyushu Univ., Grad. Sch.) MATSUNAGA HIROMI (Kyushu Univ., Grad. Sch.) TSUJI KAZUHIRO (Kyushu Univ., Grad. Sch.) MATSUMOTO RYUJI (Kyushu Univ., Grad. Sch.) MISE MASASHI (Kyushu Univ., Grad. Sch.) ITO SHOICHI (Kyushu Univ., Grad. Sch.) YAMADA HIDEYUKI (Kyushu Univ., Grad. Sch.) OGURI KAZUTA (Kyushu Univ., Grad. Sch.)

Journal Title;Xenobiotic Metabolism and Disposition

Journal Code:X0758A

ISSN:0916-1139

VOL.15;NO.Supplement;PAGE.S86-S87(2000)

Figure&Table&Reference;FIG.2, TBL.1, REF.7

Pub. Country;Japan

Language;Japanese

Abstract;Previous studies revealed that while rat CYP2B1/2 are highly inducible by phenobarbital (PB), guinea pig CYP2B18A is expressed constitutively and has low inducible nature following PB treatment. To solve the low inducibility in guinea pigs, we cloned and sequenced CYP2B18A gene. Since the intron structures of the CYP2B2 gene have not yet been determined, we sequenced this gene as well as the 2B18A gene. Comparison of gene upstream between the two genes revealed that guinea pigs lack in the phenobarbital-responsive unit (PBRU) which is demonstrated to play a crucial role in PB-mediated induction of the CYP2B2. This observation seems to support the low-inducibility of CYP2B18A. Further, NF-.KAPPA.B and RBP-J.KAPPA. binding elements, which have been reported to mediate suppression of CYP2B2 gene, were not found in the CYP2B18A gene, supporting highly constitutive expression of this gene. To clarify the mechanism underlying PB-mediated induction, we analyzed further the structure of the CYP2B2 gene in the Qdj:SD rats that lack in response to PB-mediated induction of this protein. As the results, neither large deletion nor insertion was detected in the CYP2B2 gene of this mutant rats. In addition, no mutation was detected in the PBRU region and all exons. These results suggested that impaired induction of CYP2B2 in Qdj:SD rats is due either to mutation at the region different from the PBRU or exons, or defect in trans-acting factor(s). (author abst.)

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