Disease relevance of Cyp2b10

• Recently, we performed an in vitro study to examine the effect of sub-lethal QS 755 nm lasers on the expression of p16INK4a on melanoma cell lines, and found that sub-lethal laser damage could increase DNA damage, which led to an increase in p16 expression [1].
• From this study, we identify minichromosome maintenance protein 7 (MCM7) and p16 as potentially useful biomarkers for HPV-positive head and neck cancer [2].
• This method has been successfully employed in the development of an immunoassay for HIV P24 antigen [3].
• To determine the function of P24 against immune systems in the near future, we prepared recombinant P24 antigens using Escherichia coli, insect cells infected with recombinant baculovirus and mammalian cells infected with recombinant vaccinia virus [4].

Psychiatry related information on Cyp2b10

• Experiments were performed at different postnatal ages: postnatal day 12 (P12), before eye opening; P24, corresponding roughly to the peak of the critical period for monocular deprivation, and P60, after the end of the critical period [5].

High impact information on Cyp2b10

• Here we show that the nuclear receptor CAR mediates the response evoked by a class of xenobiotics known as the 'phenobarbital-like inducers'. The strong activation of Cyp2b10 gene expression by phenobarbital, or by the more potent TCPOBOP, is absent in mice lacking the CAR gene [6].
• 32P-labeled clone p-16 alpha-1 hybridized with a single mRNA (2000 bases) that was 10 times more concentrated in liver cells from male 129/J mice than in female mice [7].
• A distal gene fragment, at about -2000 kb in CYP2B1, CYP2B2, and Cyp2b10, has been shown to be a phenobarbital-responsive enhancer independent of proximal promoter elements [8].
• Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10 [9].
• Functional analyses have identified a phenobarbital-responsive unit in the rat CYP2B1/2 and mouse Cyp2b10 genes about -2.3 kilobase pairs from the transcriptional start site, but little or no changes in protein binding to this region were observed in vitro [10].

Biological context of Cyp2b10

• In this review, progress toward understanding the mechanism of phenobarbital induction of gene expression is discussed with an emphasis on the mammalian genes, CYP2B1, CYP2B2, and Cyp2b10, which are most highly inducible by phenobarbital [8].
• Bile acid synthesis and hydroxylation were assessed by real-time RT-PCR for cytochrome P-450 (Cyp)7a1, Cyp3a11, and Cyp2b10 and mass spectrometry-gas chromatography for determination of bile acid composition [11].
• This region contained a binding site for NF-1 only in Cyp2b10 and not in Cyp2b9, but the intact site was not required for PB responsiveness [12].
• Transcriptional analysis in vivo of the hepatic genes, Cyp2b9 and Cyp2b10, by intravenous administration of plasmid DNA in mice [12].
• In this assay PB treatment increased transactivation by the Cyp2b10 PBRU about 100-fold, which is similar to the increase in the expression of the endogenous gene while the Cyp2b9 PBRU was unresponsive [12].

Anatomical context of Cyp2b10

• Characterization of phenobarbital-inducible mouse Cyp2b10 gene transcription in primary hepatocytes [13].
• The mouse hybridoma P24 had a constant cell specific production rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated production kinetics and an increased RNA content at higher growth rates [14].
• At P24, microglia often encircled neurons that were occupied with autolysosomes, indicating increased phagocytic activity [15].
• These proteins were not effected by tunicamycin treatment in cultured cells, indicating that recombinant P24 did not contain N-linked sugars [4].

Associations of Cyp2b10 with chemical compounds

• As expected, the mRNA levels of Cyp3a11, Cyp2b10, and Cyp1a2 were induced by a single dose of dexamethasone (100 mg/kg), phenobarbital (80 mg/kg), and 3-methylcholanthrene (80 mg/kg), respectively [16].
• Injection of bacterial lipopolysaccharide (LPS) induced the expected reduction in Cyp2b10 and Cyp3a mRNA levels in mouse liver [17].
• Estrogen-dependent regulation of the expression of hepatic Cyp2b and 3a isoforms: assessment using aromatase-deficient mice [18].
• In contrast, NP-treated females demonstrated a greater propensity for metabolizing zoxazolamine probably due to greater Cyp2b induction in females [19].
• Furthermore, hepatic microsomal activities for pentoxyresorufin O-dealkylation (PROD) and nifedipine oxidation, which are mainly mediated by Cyp2b and Cyp3a subfamily enzymes, respectively, were measured [20].

Physical interactions of Cyp2b10

• Purified constitutive androstane receptor (CAR)/retinoid X receptor (RXR) bound to the core NR-1 and NR-2 sites and to a third NR-3 site to the 5' side of the core in Cyp2b10 [12].

Enzymatic interactions of Cyp2b10

• SR 4233 itself inhibited benzphetamine N-demethylase, which is catalysed by Cyp2b-type enzymes but not erythromycin N-demethylase which is catalysed by Cyp3a-type isoforms [21].

Regulatory relationships of Cyp2b10

• Cyp2e1 mRNA was dramatically enhanced (12.7-fold increase) while Cyp2b10 mRNA remained unchanged and Cyp1a1 was decreased or not detected [22].

Other interactions of Cyp2b10

• In contrast Cyp2a5, Cyp2b10 and Cyp2d9 expression were elevated [23].
• In contrast, male mice treated with NP showed increased expression of Cyp2a4, Cyp2b9, and Cyp2b10 [19].
• Close linkage of the cytochrome P450IIA gene subfamily (Cyp2a) to Cyp2b and Coh on mouse chromosome 7 [24].
• The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter [25].
• Immunoinhibition studies with epitope specific monoclonal antibodies were consistent with the major involvement of phenobarbitone- and steroid-inducible products of the Cyp2b and Cyp2c subfamilies [21].

Analytical, diagnostic and therapeutic context of Cyp2b10

• Western blots confirmed induction of Cyp2b subfamily members in both males and females [19].
• Adrenalectomy increased the expression of Cyp2b9 and Cyp2b10 mRNAs, especially that of Cyp2b9 in the male liver [26].
• After 3 days the amount of cytochrome P450 2B10, as measured by pentoxy resorufin-O-dealkylase activity and immunoblotting, increased 3-fold [27].
• There were significant elevations of p16 and PCNA in all treated groups as compared to the control group (ANOVA P < 0.05) [1].
• Targeted disruption of the signal transducer and activator of transcription 5b gene (STAT5b) leads to decreased expression in male mouse liver of a male-predominant cytochrome (Cyp) 2d protein, whereas female-predominant Cyp2b proteins are increased [28].

References