Cyp1a2

..Transgenic CYP1A-humanized mice (hCYP1A-mice), which have the human CYP1A1 and CYP1A2 genes but lack the murine orthologs Cyp1a1 and Cyp1a2, provide an excellent opportunity to develop a ..

The mammalian CYP1A1, CYP1A2, and CYP1B1 genes (encoding cytochromes P450 1A1, 1A2, and 1B1, respectively) are regulated by the aromatic hydrocarbon receptor (AHR)...

..Gel shift assays revealed higher activation of nuclear factor-kappaB in WT-DB mice after APAP treatment. These findings suggest PPAR-alpha activation as a hepatoprotective adaptive response mediating protection against APAP in diabetes...

..The P450s chosen for study, CYP1A1, CYP1B1, CYP1A2, and CYP2E1, are conserved in mammals and are known to metabolize most toxicants and chemical ..

..reactive oxygen production on the aromatic hydrocarbon receptor (AHR), cytochrome P450 1A1 (CYP1A1), and cytochrome P450 1A2 (CYP1A2), proteins believed to be important in dioxin-induced liver toxicity...

b>CYP1A2 is one of the major hepatic cytochrome P450s that is involved in the metabolism of many drugs, as well as in the activation of chemical carcinogens...

..b>CYP1A1 to CYP1A2 ratios were greater in rats treated with BNF...

The aim of this study was to use the CYP1A2-null mouse to investigate the in-vivo contribution of CYP1A2 to clozapine pharmacokinetics and pharmacodynamics...

Using the Cre-lox system, we have generated a cytochrome P450 1A1 Cyp1a1(-/-) knockout mouse by deletion of the translated portions of the Cyp1a1 gene...

..0) between a locus on chromosome 9, which colocalized with the murine Cyp1a2 locus, and the plasma paraxanthine/caffeine ratio was identified...

..Mouse lines having disruption of genes encoding P450s CYP1A2, CYP2E1, and CYP1B1 were developed by use of gene disruption in empbryonic stem cells...

..responsible for this hepatic sequestration of TCDD and its congeners has been shown by our laboratory to be CYP1A2 (J. J. Diliberto, D. Burgin, and L. S. Birnbaum, 1997, Biochem. Biophys. Res. Commun. 236, 431-433)...

..In particular, it is not known whether these effects are mediated by metabolic activation of the drug. CYP1A2 is known to metabolize phenacetin in vitro...

..The P450 isoforms thought to be responsible for APAP hepatotoxicity in humans are CYP2E1, CYP1A2, and CYP3A4, and thus, we have investigated the effect of murine Cyp1a2 on APAP hepatotoxicity using Cyp1a2 ..

..In this study, we asked the question how important is the role of CYP1A1 in causing TCDD toxicity...

b>Cytochrome P450 1A2 (CYP1A2) is constitutively expressed in the mouse liver, but the constitutive expression progressively declines to an undetectable level in isolated hepatocytes...

Interindividual differences in human CYP1A1 and CYP1A2 expression appear to be associated with variability in risk toward various types of environmental toxicity and cancer...

..Real-time polymerase chain reaction (RT-PCR) showed that the expression of Cyp1a1, Cyp1a2, and OGG1genes was significantly up-regulated in mice given diets containing 375 ppm DC or more, 187...

..The data suggested that metabolism of TCDD is inherently slow, due principally to CYP1A1, and that hepatic CYP1A2 is not an active participant in the metabolism of TCDD in male mice...

..To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice...

..a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1_CYP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible ..

..The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important roles in AHR biology...

Crossing the Cyp1a1/1a2(-/-) double-knockout mouse with the Cyp1b1(-/-) single-knockout mouse, we generated the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse...

..PhIP) carcinogenesis is initiated by N(2)-hydroxylation, mediated by several cytochromes P450, including CYP1A1. However, the role of CYP1A1 in PhIP metabolic activation in vivo is unclear...

..Whereas CYP2F enzymes are widely regarded as responsible for NP bioactivation, other metabolic enzymes--including CYP1A1 and CYP1A2--produce NP-1,2-oxide in vitro...

..the inhibitory effect of a series of naturally occurring trans-resveratrol analogues on cytochromes P450, namely CYP1A2 and CYP2E1, in vitro in order to analyse any structure-activity relationships...

..The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated by the aryl hydrocarbon receptor...

b>CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene, to reactive intermediates associated with toxicity, mutagenesis, and carcinogenesis...

..By contrast, the total cytochrome P450 (CYP) content and the expression of Cyp1a2 were down-regulated by the treatment...

..In contrast, uroporphyria was not detected in Cyp1a2(-/-) knockout mice, although expression of CYP1A1 and CYP2B10 was greatly induced...

..4. Also discussed are null mouse lines with targeted mutations in genes encoding receptors having primary roles in Cyp gene regulation...

..Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis...

..Using the DNA binding site for the aryl hydrocarbon receptor as a probe, gel retardation analyses showed that phenobarbital treatment induced protein binding, regardless of the presence of the aryl hydrocarbon receptor...

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..Chromosome segregation analysis of 12 hybrid clones demonstrated that the structural genes for both P1-450 and P3-450 can be assigned to mouse chromosome 9...

..These data support the likelihood that cysteine 456 is the thiolate ligand to the heme iron in the P3-450 enzyme active-site...

..These data demonstrate conclusively that pBR322 clone 46 DNA is associated with mRNA controlled by the murine Ah locus, presumably the structural gene encoding 3-methylcholanthrene-induced P(1)-450...

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..0 and 7.4 kb) were assigned to Chinese hamster chromosome 4. These data are consistent with linkage conservation among these two P-450 sequences and four other loci on mouse chromosome 9 that map to hamster chromosome 4...

..This report shows the varying degree of structural relatedness among the isozymes examined and demonstrates the suitability and advantage of immunopurified cytochromes P-450 for sequencing and structural studies...

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..Conversely, there are no detectable basal levels of cytochrome P1450 (Cyp1a1 gene) or cytochrome P3450 (Cyp1a2 gene) mRNA, indicating that the regulation of basal expression of the Cyp1a1 and ..

..It is of interest that the same nine bases are found in intron 2 about 80 bp upstream from the 5' end of exon 3 in the homologous P3450 gene...

..These results emphasize the interest of using Mus musculus musculus inbred strains to establish interspecific crosses, particularly when considering their breeding performances...

..The expression of 3-methylcholanthrene (MCA)-induced CYP1A1 mRNA remained high during the observation period under both monolayer and spheroid culture conditions...

..The 3' terminal exon of P1-450 is about 500 bp longer than that of P3-450. These data suggest that both P1-450 and P3-450 have diverged from a common ancestral gene...

..BD) compounds were used to investigate the structural requirement for regulation of the cytochrome P450 isozymes, CYP1A1, CYP1A2 and CYP2B10, in mouse liver...

..Immunocytochemical localization of the P-450 enzyme CYP1A2, which is responsible for the primary activation of these mutagens, shows that in untreated mice it is present in ..

..The differential inducibility of liver CYP1A1 mRNA by dioxin was therefore compared in Cyp1a2(+/+) wild-type mice, Cyp1a2(+/-) heterozygotes, and Cyp1a2(-/-) ..

..5-fold higher than in Cyp1a2(-/-) mice. Treatment with MC increased hepatic CYP1A1 in both mouse lines and hepatic CYP1A2 only in the Cyp1a2(+/+) line, as determined by Western immunoblotting...

..Transgenic mice lacking a cytochrome P450 1A2 gene were used to study the influence of the CYP1A2 gene on the hepatic sequestration and distribution of ..

..Our finding of cerebellum-specific coregulation suggests that distinct sets of target genes regulated by the ROR alpha1 and ROR alpha4 isoforms are required for Purkinje cell development...

..cytoplasmic change) in the glandular stomach, respiratory tract, bile duct, and gall bladder of B6,129 CYP1A2-null and wild-type mice as well as in both sexes of the background 129S4/SvJae strain...

..The mouse loci have been named Myo1e, Myo1c, and Myo9b; they map to chromosomes 9 (MGD position 41), 11 (MGD position 46), and 8 (MGD position 31.5), respectively...

..Analysis of nuclear [3H]TCDD dioxin receptor by sucrose density gradients demonstrated that the inhibition of Cyp1a gene transcription and DNA binding by TPA resulted from a reduction in nuclear dioxin receptor concentration...

Expression of Cyp1a1 and Cyp1a2 genes was investigated in adult C57BL/6NCrj mouse hepatocytes in primary culture for up to 5 days...

b>Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance...

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..Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene family...

..Using interspecies backcrosses, we have localized Tpm-1 on mouse chromosome 9, cen-Cyp1a2-Tpm-1-Mod-1-Mylc-Scn5a, near the d-se region...

..Induction of CYP1A1, CYP1A2, and UGT1*06 mRNAs by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin was absent in livers of Arnt-..

..Notably, a C-4 zinc finger type motif is recognized in human and mouse ClpX. This motif of so far unknown function is present only in a subset of the known ClpX sequences...

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TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) induces cytochromes P450 (CYPs) such as CYP1A1 and CYP1A2 via activation of the aromatic hydrocarbon receptor (AHR)...

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..2. To determine the mechanism for the TCDD-mediated oxidative stress response in mice, using Ahr, Cyp1a1 and cyp1a2 knockout mice. 3...

..Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. ..

The long-term goal of this project is to understand the role of cytochrome P450 1A1 (CYP1A1) in toxicity caused by environmental pollutants...

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..These studies will enhance our understanding of heavy metal toxicity by identifying and characterizing, for the first time, a major gene responsible for susceptibility to cadmium-induced toxicity. ..

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..g. grilled foods & cigarette smoke. Cytochromes P450 1A1 & 1B1 (CYP1A1, CYP1B1) are responsible for the metabolism of numerous PAHs, the prototype of which is benzo[a]pyrene (BaP)...

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..g. grilled foods & cigarette smoke. Cytochromes P450 1A1 & 1B1 (CYP1A1, CYP1B1) are responsible for the metabolism of numerous PAHs, the prototype of which is benzo[a]pyrene (BaP)...

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Cytochromes P450 1B1, 1A1 & 1A2 (CYP1B1, CYP1A1, and CYP1A2) are responsible for both detoxifying and metabolically activating innumerable polycyclic aromatic hydrocarbons (PAHs), nitrosamines, and A/-heterocyclics present in ..

..dioxin in various, tissues (bone marrow, liver, developing embryo) of the Cyp1a1(-/-) knockout and Cyp1a1(+/+) wild-type mouse as a function of dose of the environmental pollutant and route of ..

The long-term goal of this project is to understand the role that the CYP1A2 (cytochrome P3450) enzyme plays in genotoxicity caused by environmental pollutants in the intact mouse...

..b>Cyp1a1 is a member of the dioxin-inducible [ah] battery, the genes of which are up-regulated by the ah receptor (AHR)...

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..from the Investigator's Abstract) The long-term goal of this project is the elucidation of cytochrome P450 CYP1A2's role in toxicity and cancer caused by environmentally hazardous chemicals...