Disease relevance of CYP1A1

• A truncated construct of the turkey CYP1A5 gene with 29 amino acids deleted from the hydrophobic NH2-terminal region was cloned and heterologously expressed in Escherichia coli [1].

High impact information on CYP1A1

• Induction of tamoxifen-4-hydroxylation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and phenobarbital (PB) in avian liver: identification of P450 TCDDAA as catalyst of 4-hydroxylation induced by TCDD and beta NF [2].
• Northern analysis shows that the chick enzymes have a different tissue distribution from CYP1A1 and -1A2 [3].
• Amino acid sequence analysis shows that although each chick enzyme can be classified in the CYP1A family, both are more like CYP1A1 than -1A2, and neither can be said to be directly orthologous to CYP1A1 or -1A2 [3].
• The P-450s exhibit catalytic selectivity either for arachidonic acid metabolism, particularly epoxygenation (P-450 TCDDAA, 55 kDa), or for aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin deethylase (7-EROD) (P-450 TCDDAHH, 54.5 kDa) [4].
• Spatial heterogeneity in phylogenetic signal along the sequences strongly indicated that cormorant CYP1A4 and CYP1A5 have undergone partial interparalog gene conversion, similar to chicken and mammalian CYP1As [5].

Biological context of CYP1A1

• Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events [6].
• Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5 [6].
• Basal and TCB-inducible CYP1A5 mRNA expression was maximal in liver at 8 days of development and remained high throughout the remainder of embryonic development [7].
• Hepatic CYP1A4 and CYP1A5 mRNA levels in wild cormorants from Lake Biwa, Japan, were quantified to examine the effects of DRCs on isoform-specific expression and to evaluate the toxicokinetics of DRCs in which CYP1A expression is involved [5].
• A partial gene sequence for CYP1A5 indicated that the intron/exon organization of this gene was identical to that of the CYP1A1 and CYP1A2 mammalian genes and was present in a single copy in the genome [7].

Anatomical context of CYP1A1

• CYP1A4 alone was extensively induced in the cardiovascular system, in cardiac myocytes, in perivascular cells having the same location as impulse-conducting Purkinje cells, and like CYP1A1, in vascular endothelium in every organ examined [8].
• Also, TCDD induced CYP1A4 but not 1A5 in both myocardium and heart vessels whereas CYP1A1 induction has only been found in endocardium [9].
• In all three species, BNF induced a protein immunoreactive with monoclonal antibody to CYP1A1 from the marine fish Stenotomus chrysops (scup), but a CYP1A2-like protein was not detected in avian microsomes probed with polyclonal antibodies to mouse CYP1A2 [10].
• The purpose of this study was to examine the developmental regulation of the second dioxin-inducible P450 gene, CYP1A5, in chick embryo liver [7].
• Concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on CYP1A4 and CYP1A5 mRNA abundance were detected in fresh and post-EROD hepatocyte cultures [11].

Associations of CYP1A1 with chemical compounds

• One, designated CYP1A5, was preferentially active in arachidonic acid epoxygenation and the other, designated CYP1A4, in 7-ethoxyresorufin deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH), reactions mainly catalyzed by CYP1A1 in rodents [12].
• Further, liver CYP1A4 and 1A5 mRNAs had the same half lives and were both superinduced by cycloheximide, whereas mRNA half lives differ for CYP1A1 and 1A2, and cycloheximide superinduces only CYP1A1 [9].
• Both CYP1A4 and CYP1A5 mRNA levels were positively correlated with total tetrachlorodibenzo-p-dioxin toxic equivalents and concentrations of each congener in most cases in the liver, suggesting the induction of both enzymes through a shared transcriptional mechanism [5].
• In contrast to a previous report that CYP1A5 mRNA expression was inducible by estradiol, we observed no effects of estradiol or dexamethasone on CYP1A5 mRNA expression, either alone or in combination with TCB [7].
• Effect of arsenite on the induction of CYP1A4 and CYP1A5 in cultured chick embryo hepatocytes [13].

Regulatory relationships of CYP1A1

• Ah receptor ligands induce formation of CYP1A1 and 1A2 in mammals and of a different set of enzymes, CYP1A4 and 1A5, in chicks [8].
• Thus, CYP1A5 appears to be regulated in a very similar manner to CYP1A4 in chick embryo liver [7].

Other interactions of CYP1A1

• Ah receptor activation leads to the induction of cytochrome P450 (CYP) 1A enzymes, which include CYP1A1 and 1A2 in mammals and CYP1A4 and 1A5 in chickens [9].

Analytical, diagnostic and therapeutic context of CYP1A1

• On Western blots non-immunopurified anti-TCDDAA and anti-TCDDAHH antisera recognized rat and guinea pig CYP1A1 and CYP1A2 [4].
• Phylogenetic analysis shows that the two chick enzymes form a separate branch in the CYP1A family tree distinct from mammalian CYP1A1 and -1A2 and from fish CYP1A enzymes [3].
• JC CYP1A5 mRNA expression measured by real-time RT-PCR had a significant positive correlation with hepatic TEQs, suggesting induction of CYP1A5 at the transcriptional level [14].

References