ArticleBiochemical pharmacology2016
Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Perfluorooctane sulfonate (PFOS) interferes with Cyp1a activity and dysregulates the aryl hydrocarbon receptor pathway in larval zebrafish (Danio rerio).Environmental pollution (Barking, Essex : 1987) · 2026Article
- CYP1A1 as a conserved metabolic circuit linking environmental sensing to immune regulation.Archives of toxicology · 2026Review
- Discovery of a novel AhR-CYP1A1 axis activator for mitigating inflammatory diseases using anActa pharmaceutica Sinica. B · 2025Article
- Disrupting Development: Unraveling the Interplay of Aryl Hydrocarbon Receptor (AHR) and Wnt/β-Catenin Pathways in Kidney Development Under the Influence of Environmental Pollutants.Biological trace element research · 2024Article
- The influence of AHR on immune and tissue biology.EMBO molecular medicine · 2024Review
- Article
- Differential cell type-specific function of the aryl hydrocarbon receptor and its repressor in diet-induced obesity and fibrosis.Molecular metabolism · 2024Article
- Light Sensing beyond Vision: Focusing on a Possible Role for the FICZ/AhR Complex in Skin Optotransduction.Cells · 2024Review
- Article
- Implications of xenobiotic-response element(s) and aryl hydrocarbon receptor in health and diseases.Human cell · 2023Review
- Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation.Cell & bioscience · 2023Review
- Endogenous AhR agonist FICZ accumulates in rainbow trout (Oncorhynchus mykiss) alevins exposed to a mixture of two PAHs, retene and fluoranthene.Ecotoxicology (London, England) · 2022Article
- Development and Applications of a Zebrafish (Toxics · 2022Article
- Ancestral Sequence Reconstruction of a Cytochrome P450 Family Involved in Chemical Defense Reveals the Functional Evolution of a Promiscuous, Xenobiotic-Metabolizing Enzyme in Vertebrates.Molecular biology and evolution · 2022Article
- Oxidative stress inducers potentiate 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated pre-cardiac edema in larval zebrafish.The Journal of veterinary medical science · 2021Article
- Dibenzyl trisulfide binds to and competitively inhibits the cytochrome P450 1A1 active site without impacting the expression of the aryl hydrocarbon receptor.Toxicology and applied pharmacology · 2021Article
- The sulfate metabolite of 3,3'-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio).Chemosphere · 2020Article
- A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- An Endogenous Ligand of Aryl Hydrocarbon Receptor 6-Formylindolo[3,2-b]Carbazole (FICZ) Is a Signaling Molecule in Neurogenesis of Adult Hippocampal Neurons.Journal of molecular neuroscience : MN · 2020Article
- The emerging contaminant 3,3'-dichlorobiphenyl (PCB-11) impedes Ahr activation and Cyp1a activity to modify embryotoxicity of Ahr ligands in the zebrafish embryo model (Danio rerio).Environmental pollution (Barking, Essex : 1987) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
6-Formylindolo[3,2-b]carbazole (FICZ) is a potent aryl hydrocarbon receptor (AHR) agonist that is efficiently metabolized by AHR-regulated cytochrome P4501 enzymes. FICZ is a proposed physiological AHR ligand that induces its own degradation as part of a regulatory negative feedback loop. In vitro studies in cells show that CYP1 inhibition in the presence of FICZ results in enhanced AHR activation, suggesting that FICZ accumulates in the cell when its metabolism is blocked. We used zebrafish (Danio rerio) embryos to investigate the in vivo effects of FICZ when CYP1A is knocked down or inhibited. Embryos were injected with morpholino antisense oligonucleotides targeting CYP1A (CYP1A-MO), Ahr2, or a combination of both. FICZ exposure of non-injected embryos or embryos injected with control morpholino had little effect. In CYP1A-MO-injected embryos, however, FICZ dramatically increased mortality, incidence and severity of pericardial edema and circulation failure, reduced hatching frequency, blocked swim bladder inflation, and strongly potentiated expression of Ahr2-regulated genes. These effects were substantially reduced in embryos with a combined knockdown of Ahr2 and CYP1A, indicating that the toxicity was mediated at least partly by Ahr2. Co-exposure to the CYP1 inhibitor alpha-naphthoflavone (αNF) and FICZ had similar effects as the combination of CYP1A-MO and FICZ. HPLC analysis of FICZ-exposed embryos showed increased levels of FICZ after concomitant CYP1A-MO injection or αNF co-exposure. Together, these results show that a functioning CYP1/AHR feedback loop is crucial for regulation of AHR signaling by a potential physiological ligand in vivo and further highlights the role of CYP1 enzymes in regulating biological effects of FICZ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.