Disease relevance of Cyp2a

• In hepatomas from male mice, the Cyp2a-containing cells became dispersed [1].

High impact information on Cyp2a

• These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored glycogen [2].
• A previously reported cDNA clone [pP450(1)] coding for a phenobarbital-inducible cytochrome P-450 variant of rat liver microsomal membranes, designated P-450e(U.C.), was used as a specific hybridization probe to screen a human liver cDNA library [3].
• One of the repressor binding sites, the barbie box, is present in many mammalian phenobarbital-inducible genes, including the promimal promoter regions of CYP2B1, CYP2B2, and Cyp2B10 [4].
• These findings strongly suggest that the phenobarbital-inducible apoptosis is mediated by Bax [5].
• The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice [6].

Biological context of Cyp2a

• We have resolved this apparent anomaly between the genetic and biochemical data by showing that genes from the P450IIA subfamily (Cyp2a) are closely linked to Coh and to Cyp2b on mouse chromosome 7 [7].
• Consistent with the Q-PCR data, Western blots showed dose-dependent downregulation of Cyp3a only in females and induction of Cyp2a only in males [8].
• In hepatomas, this localisation is perturbed; in females we observed a focal cell localisation, and the Cyp2a-containing cells were often hypertrophic and polyploid [1].
• Southern blot analysis suggests that multiple sequences homologous to a phenobarbital-inducible cytochrome P-450 cDNA are present in the rat and mouse genomes [9].
• Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice [9].

Anatomical context of Cyp2a

• The microsomes gave staining bands with all these antibodies, suggesting the presence of mouse Cyp2a, 2b, and 4a isoforms in RAW264 [10].
• The constitutive expression of phenobarbital-inducible mouse cytochrome P-450 (I-P-450(16 alpha) at the mRNA level and its associated testosterone 16 alpha-hydroxylase activity in liver microsomes was a female characteristic in many inbred mice, including BALB/cJ, A/HeJ, and C57BL/6J [11].
• Characterization of phenobarbital-inducible mouse Cyp2b10 gene transcription in primary hepatocytes [12].
• Mab specific for phenobarbital-inducible cytochromes P-450, Mab 2-66-3, reacted with parenchymal and bronchiolar epithelial cells in the lungs of phenobarbital-treated, 3-methylcholanthrene-treated, and untreated mice [13].

Associations of Cyp2a with chemical compounds

• Coumarin 7-hydroxylation activities (marker for Cyp2a) were decreased to 0.7-fold in the male jvs/jvs-type mice [14].
• This may suggest that P450Coh has a closer association to the steroid 15 alpha-hydroxylase gene family than to the P450IIB subfamily of phenobarbital-inducible isoenzymes [15].
• These antioxidants also prevented the repressive effects of LPS on dexamethasone-, rifampicin-, mifepristone-, and phenobarbital-inducible CYP3A11 mRNA expression and ERND catalytic activity in mouse liver [16].
• Pretreatment with a single dose of gadolinium chloride (10 mg/kg) also significantly attenuated LPS-induced downregulation of dexamethasone-, rifampicim-, mifepristone-, and phenobarbital-inducible, CYP3A11 mRNA expression and ERND activity in mouse liver [16].
• Allopurinol and diphenyleneiodonium chloride pretreatment also attenuated the repressive effects of LPS on dexamethasone-, rifampicin-, mifepristone-, and phenobarbital-inducible CYP3A11 mRNA expression and ERND catalytic activity in mouse liver [16].

Other interactions of Cyp2a

• An analysis of two sets of multilocus crosses revealed that the Akt2 gene is closely linked to the Cyp2a locus in proximal MMU7 [17].
• Both the constitutive and phenobarbital-inducible expression of Cyp2b-9 and Cyp2b-10 mRNA decreased rapidly after transferring the hepatocytes to monolayer culture [18].
• A cDNA (pP-450b-5) to a major phenobarbital-inducible cytochrome P-450 mRNA species in the rat detected 6 polymorphic DNA fragments when hybridized to DNA from C57BL/6J and DBA/2J mice restricted with endonucleases EcoRI, BamHI, and PvuII [9].
• Nucleotide homology between a member of either gene subfamily is about 30%, and protein homology is about 15%, suggesting that the Ah locus-associated P-450 gene subfamily diverged from the phenobarbital inducible P-450 subfamily more than 200 million years ago [19].

Analytical, diagnostic and therapeutic context of Cyp2a

• Regulation of phenobarbital-inducible cytochrome P-450s in rat and mouse liver following dexamethasone administration and hypophysectomy [20].
• Antiserum raised to the phenobarbital-inducible form of rat liver cytochrome P-450 [P-450(b+e)] inhibited mouse brain aminopyrine N-demethylase activity by around 80+ mouse brain microsomal protein exhibited cross-reactivity against this antiserum when examined by Ouchterlony double diffusion and immunoblotting [21].

References