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Characterization of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

ABSTRACT: Characterization of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

PROVIDER: PRJNA1132981 | ENA |

REPOSITORIES: ENA

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Mutational signatures of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Project description:Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Whole genome sequencing revealed a higher frequency of T>G base substitution mutations in worms expressing human CYP1A1;EPHX thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research.

2025-06-24 | GSE272108 | GEO

Characterization of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Project description:Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are produced by the incomplete combustion of organic matter and thus are present in tobacco smoke, charbroiled food and diesel exhaust. The nematode Caenorhabditis elegans lacks the genetic components of the classical mammalian cytochrome P450 (CYP)-mediated BaP-diol-epoxide metabolism pathway thus CYP1A1 or CYP1A2 together with human epoxide hydrolase (EPHX) was introduced into the worm genome, thereby allowing to study potential physiological, genomic and transcriptional changes after BaP exposure in these CYP-humanised C. elegans strains. Strain and exposure specific changes in the transcriptome were identified by means of RNAseq. thereby demonstrating the amenity of introducing human genes into the C. elegans genome and their utility to serve as a model for environmental carcinogenesis and pharmacological research.

2025-06-24 | GSE271716 | GEO

Mutational signatures of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

Project description:Mutational signatures of genome-modified Caenorhabditis elegans expressing the human cytochrome P450 (CYP1A1 and CYP1A2) pathway

| PRJNA1135132 | ENA

Identification and developmental expression of the full complement of cytochrome P450 genes in zebrafish

Project description:To determine the expression of cytochrome P450 genes during normal development

2010-10-21 | GSE24840 | GEO

Identification and developmental expression of the full complement of cytochrome P450 genes in zebrafish

Project description:To determine the expression of cytochrome P450 genes during normal development Zebrafish embryos were collected at 3, 6, 12, 24, 36, and 48 hours post fertilization. Quadruplicate biological replicates of 100 embryos were hybridized.

2010-10-21 | E-GEOD-24840 | biostudies-arrayexpress

Arylhydrocarbon receptor and the cytochrome P450 enzyme CYP1B1 prevent exacerbation of allergic airway inflammation

Project description:Signaling via the arylhydrocarbon receptor (AhR) is thought to contribute to exacerbation of allergic asthma by anthropogenic pollution. The physiological role of AhR and its downstream targets CYP1 family members upon exposure to aeroallergens remain unknown. We seek to characterize the role of the AhR pathway for the regulation of allergic airway inflammation (AAI). We employed knockout animals of the AhR and its downstream target cytochrome P450 enzymes CYP1A1, CYP1A2 and CYP1B1 and subjected them to preclinical allergic asthma models (ragweed and house dust mite) to assess the role of AhR and CYP1 family members in allergic airway inflammation. Histological, transcriptional and functional assays were used to uncover relevant cell types and mechanistic insights. In the ragweed model, AhRKO/KO and CYP1B1KO/KO but not CYP1A2 KO/KO or CYP1A2KO/KO animals showed exacerbation of AAI including elevated infiltration of cells in the bronchoalveolar lavage fluid and increased serum levels of IgE and allergen-specific IgG1. AhR KO/KO and CYP1B1KO/KO animals showed also more severe reactions in HDM-induced allergic AAI. Bone marrow chimeras as well as qPCR analysis and immune fluorescence histology indicate that expression of CYP1B1 in non-hematopoietic cells – presumably lung epithelial cells – is necessary to prevent exacerbation of HDM-induced AAI. Mechanistically, we show that CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and thus potentially to deprivation from endogenous AhR ligands. Transcriptional analysis of primary lung epithelial cells indicates a functional link of the AhR to regulation of circadian clock genes at baseline and massive alteration of gene expression upon allergen exposure.

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Fetal to adult ontogeny of human cytochrome P450 activity, abundance, and expression

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Project description:The mosquito Aedes aegypti serves as the primary vector for dengue virus (DENV), a human pathogen responsible for infecting hundreds of millions of people globally each year. Natural populations of Ae. aegypti show significant variability in their ability to become infected with DENV, which is largely governed by mosquito genetic factors. Previous studies suggest that genes encoding digestive enzymes, such as trypsins, and canonical antiviral immune genes may contribute to this variation 5-10. However, the specific causal gene variants underlying DENV susceptibility in Ae. aegypti are unknown. Here, we identify a gene encoding a cytochrome P450 (CYP4G15) whose genetic variants drive differences in DENV susceptibility in a natural Ae. aegypti population. CYP4G15 is transiently overexpressed in the midguts of DENV-resistant mosquitoes early in infection. Knockdown of CYP4G15 expression increases DENV susceptibility, while transgenic overexpression enhances resistance. A naturally occurring CYP4G15 variant with an 18-base-pair deletion in its promoter shows reduced expression and confers higher DENV susceptibility. The identification of CYP4G15 as a factor underlying DENV susceptibility in Ae. aegypti is unexpected because cytochrome P450 enzymes are typically associated with metabolism. Our finding challenges the long-standing focus on canonical immune pathways and opens new avenues for understanding antiviral defense and DENV transmission in mosquitoes.

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Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling

Project description:Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling

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Identification of genes responding to the activity of the Arabidopsis cytochrome P450 KLUH/CYP78A5

Project description:The Arabidopsis cytochrome P450 KLUH (KLU)/CYP78A5 promotes organ growth in a non-cell autonomous manner. To identify genes regulated by KLU activity, homozygous klu-2 mutants carrying constructs for EtOH-inducible overexpression of wild-type KLU (35S::AlcR-AlcA::KLU) or of enzymatically inactive KLU protein (35S::AlcR-AlcA::KLUmut) were induced with EtOH and sampled at 90 min and 240 min after induction for gene expression changes. Keywords: Time course, genetic modification

2007-12-04 | GSE9201 | GEO

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