High impact information on Cyp2b2

• Most significant of these differences was the relatively weak induction of CYPIIB1 but striking induction of CYPIIB2 by tamoxifen [1].
• Thio-TEPA depletion and TEPA formation catalyzed by phenobarbital-induced liver microsomes were both inhibited by greater than 90% by antibodies selectively reactive with P-450 PB-4 (gene product IIB1), the major phenobarbital-inducible rat liver microsomal P-450 form, but not by antibodies inhibitory toward 7 other rat hepatic P-450s [2].
• Oxidation of thio-TEPA to TEPA was also catalyzed by purified P-450 PB-4 (Km (app) 19 microM; Vmax (app) = 11 mol thio-TEPA metabolized/min/mol P-450 PB-4) following reconstitution of the cytochrome with NADPH P-450 reductase in a lipid environment [2].
• These results demonstrate that, in vivo, phenobarbital induction and tissue-specific control requires interaction of regulatory elements far upstream of the core CYP2B2 promoter region and upstream of motifs indicated previously as determinants of phenobarbital responsiveness [3].
• Expression in mouse tissues was analyzed for two series of rat CYP2B2 gene constructs, of 19 and 39 kilobase pairs total length, each containing the entire coding region, introns, and 3'-flanking sequences of CYP2B2, but differing in the respective lengths of 5'-flanking sequence [3].

Biological context of Cyp2b2

• About 3 kb of the promoter region of the gene encoding cytochrome P-450 2B2 (CYP2B2) in the rat were sequenced and searched for potential cis-acting elements [4].
• The use of a deletion series of this template in in vitro transcription assays, provided evidence that the BRE serves as a major cis-acting element in the (regulated) transcription activation of the CYP2B2 gene [4].
• Although it is unclear whether P-450 PB-4 and P-450 PB-5 are separate gene products or are related by post-translational modifications, this present demonstration of closely related isozymic forms suggests the possible added complexity of microheterogeneity for this family of microsomal monooxygenases [5].
• Very similar substrate specificity profiles were evident when the two isozymes were reconstituted with lipid, cytochrome P-450 reductase, and cytochrome b5 for oxidative metabolism of several xenobiotics, although P-450 PB-4 exhibited a higher specific catalytic activity (greater than or equal to 5-fold) with all substrates tested [5].
• Null phenotype for cytochrome P450 2B2 in the rat results from a deletion of its structural gene [6].

Anatomical context of Cyp2b2

• Fractionation of cell homogenates into cytosol and microsomes revealed that the P-450 PB-4-mediated activities are associated with the membrane fraction [7].
• Homogenates prepared from the parental cell line V79, which does not express detectable levels of P-450 PB-4 or any other cytochrome P-450, exhibited no androgen 16 beta- or 16 alpha-hydroxylase activity [7].
• Androgen hydroxylation catalysed by Chinese hamster fibroblast SD1 cells, which stably express cytochrome P-450 form PB-4, the rat P450IIB1 gene product, was assessed and compared to that catalysed by purified cytochrome P-450 PB-4 isolated from rat liver [7].
• Xenobiotic induction of P-450 PB-4 (IIB1) and P-450c (IA1) and associated monooxygenase activities in primary cultures of adult rat hepatocytes [8].

Associations of Cyp2b2 with chemical compounds

• Three antipeptide antibodies raised against hydrophilic segments located in the amino-terminal one-third of P-450 PB-4 markedly inhibited the P-450 PB-4-catalyzed O-deethylation of the model substrate 7-ethoxycoumarin [9].
• Cytochrome P450 2B1, encoded by CYP2B1, and cytochrome P450 2B2, encoded by CYP2B2, are inducible in rat liver by phenobarbital (PB) [10].
• SD1 cell homogenates catalysed the NADPH-dependent hydroxylation of androstenedione and testosterone with a regioselectivity very similar to that purified by P-450 PB-4 (16 beta-hydroxylation/16 alpha-hydroxylation = 6.0-6.8 for androstenedione; 16 beta/16 alpha = 0.9 for testosterone) [7].
• [125I]TID incorporation into microsomal P-450 PB-4 was inhibited in a dose-dependent manner by the P-450 PB-4 substrate benzphetamine [11].
• Because ethylated fixed-ring tamoxifen, toremifene, and 4-iodotamoxifen had differential activities in the two assays, we conclude that CYPIIB2 induction and GSTA1 suppression by triphenylethylenes are the result of two separate and distinct mechanistic pathways [12].

Other interactions of Cyp2b2

• In contrast, only minor differences between the cell types were apparent in the expression of cytochromes P-450 PB-4, P-450 MC1a, P-450 MC1b and microsomal epoxide hydrolase [13].

Analytical, diagnostic and therapeutic context of Cyp2b2

• Although each antipeptide immunoprecipitated both purified 125I-labeled P-450 PB-4 and also in vitro-synthesized apo-P-450 PB-4, the yields of immunoprecipitation were low relative to that obtained using anti-P-450 heterosera [9].
• Each of the antipeptide antibodies recognized purified P-450 PB-4 and the highly homologous P-450 PB-5 as demonstrated by a solid-phase enzyme-linked immunosorbent assay [9].
• Increases in CYPIIB1, CYPIIB2, CYPIIIA, and microsomal epoxide hydrolase mRNA and protein levels in males and females were observed by Western and Northern blotting [1].
• Analyses of restriction digests and specific polymerase chain reaction products of hepatic DNAs revealed that the basis for the null phenotype of CYP2B2 in M520 and WM rats was a deletion of the CYP2B2 gene [6].
• The measured mass of cytochrome P450 2B2 with MALDI/TOF resulted in an average molecular weight which was higher than reported values [14].

References