ArticleToxicological sciences : an official journal of the Society of Toxicology2015
AHR2-Mediated transcriptomic responses underlying the synergistic cardiac developmental toxicity of PAHs.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
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- Benzo(a)pyrene and cardiovascular diseases: An overview of pre-clinical studies focused on the underlying molecular mechanism.Frontiers in nutrition · 2022Review
- Concentration-response gene expression analysis in zebrafish reveals phenotypically-anchored transcriptional responses to retene.Frontiers in toxicology · 2022Article
- Heart development in two populations of Atlantic killifish (Fundulus heteroclitus) following exposure to a polycyclic aromatic hydrocarbon mixture.Ecotoxicology and environmental safety · 2021Article
- A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- The sulfate metabolite of 3,3'-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio).Chemosphere · 2020Article
- Aryl Hydrocarbon Receptor Mediates Larval Zebrafish Fin Duplication Following Exposure to Benzofluoranthenes.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Effects of 9,10-phenanthrenequione on antioxidant indices and metabolite profiles inRoyal Society open science · 2020Article
- Transcriptomic changes in western mosquitofish (Gambusia affinis) liver following benzo[a]pyrene exposure.Environmental science and pollution research international · 2020Article
- Particulate Matter 2.5 Induced Developmental Cardiotoxicity in Chicken Embryo and Hatchling.Frontiers in pharmacology · 2020Article
- Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard.International journal of molecular sciences · 2019Article
- Genome-wide scan reveals signatures of selection related to pollution adaptation in non-model estuarine Atlantic killifish (Fundulus heteroclitus).Aquatic toxicology (Amsterdam, Netherlands) · 2018Article
- Characterization of AHR2 and CYP1A expression in Atlantic sturgeon and shortnose sturgeon treated with coplanar PCBs and TCDD.Aquatic toxicology (Amsterdam, Netherlands) · 2018Article
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- A bioenergetics assay for studying the effects of environmental stressors on mitochondrial function in vivo in zebrafish larvae.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Polycyclic aromatic hydrocarbons (PAHs) induce developmental defects including cardiac deformities in fish. The aryl hydrocarbon receptor (AHR) mediates the toxicity of some PAHs. Exposure to a simple PAH mixture during embryo development consisting of an AHR agonist (benzo(a)pyrene-BaP) with fluoranthene (FL), an inhibitor of cytochrome p450 1(CYP1)--a gene induced by AHR activation--results in cardiac deformities. Exposure to BaP or FL alone at similar concentrations alters heart rates, but does not induce morphological deformities. Furthermore, AHR2 knockdown prevents the toxicity of BaP + FL mixture. Here, we used a zebrafish microarray analysis to identify heart-specific transcriptomic changes during early development that might underlie cardiotoxicity of BaP + FL. We used AHR2 morphant embryos to determine the role of this receptor in mediating toxicity. Control and knockdown embryos at 36 h post-fertilization were exposed to DMSO, 100 μg/l BaP, 500 μg/l FL, or 100 μg/l BaP + 500 μg/l FL, and heart tissues for RNA were extracted at 2, 6, 12, and 18 h-post-exposure (hpe), prior to the appearance of cardiac deformities. Data show AHR2-dependent BaP + FL effects on expression of genes involved in protein biosynthesis and neuronal development in addition to signaling molecules and their associated molecular pathways. Ca(2+)-cycling and muscle contraction genes were the most significantly differentially expressed category of transcripts when comparing BaP + FL-treated AHR2 morphant and control embryos. These differences were most prominent at 2 and 6 hpe. Therefore, we postulate that BaP + FL may affect cellular Ca(2+) levels and subsequently cardiac muscle function, potentially underlying BaP + FL cardiotoxicity.
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