ArticleToxicology and applied pharmacology2014
Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines.
Article in Toxicology and applied pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
- Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology.Environmental and molecular mutagenesis · 2025Review
- A dynamic model of gene activation in response to hypoxia accounting for both HIF-1 and HIF-2.Briefings in functional genomics · 2025Article
- Effects of Naphtho[2,1-Environmental health perspectives · 2024Article
- AI-driven Discovery of Morphomolecular Signatures in Toxicology.bioRxiv : the preprint server for biology · 2024Article
- Magnetophoretic circuits: A review of device designs and implementation for precise single-cell manipulation.Analytica chimica acta · 2023Review
- New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Multi-level interaction between HIF and AHR transcriptional pathways in kidney carcinoma.Life science alliance · 2023Article
- Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway.Biochemical pharmacology · 2023Review
- A Gedunin-Type Limonoid, 7-Deacetoxy-7-Oxogedunin, from Andiroba (International journal of molecular sciences · 2022Article
- Comparative analysis of long noncoding RNA and mRNA expression provides insights into adaptation to hypoxia in Tibetan sheep.Scientific reports · 2022Article
- Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters.FEBS letters · 2021Article
- Ent-kaurane-type diterpenoids from Isodonis Herba activate human hair follicle dermal papilla cells proliferation via the Akt/GSK-3β/β-catenin transduction pathway.Journal of natural medicines · 2021Article
- A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes.International journal of molecular sciences · 2021Review
- Reoxygenation induces reactive oxygen species production and ferroptosis in renal tubular epithelial cells by activating aryl hydrocarbon receptor.Molecular medicine reports · 2021Article
- Hydrostatic pressure regulates CYP1A2 expression in human hepatocytes via a mechanosensitive aryl hydrocarbon receptor-dependent pathway.American journal of physiology. Cell physiology · 2020Article
- Hypoxia Inducible Factor 1α Inhibits the Expression of Immunosuppressive Tryptophan-2,3-Dioxygenase in Glioblastoma.Frontiers in immunology · 2019Article
- The aryl hydrocarbon receptor-cytochrome P450 1A1 pathway controls lipid accumulation and enhances the permissiveness for hepatitis C virus assembly.The Journal of biological chemistry · 2018Article
- Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126.Archives of toxicology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The aryl hydrocarbon receptor (AhR) is an important mediator of toxic responses after exposure to xenobiotics including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like polychlorinated biphenyls (PCBs). Activation of AhR responsive genes requires AhR dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT), a heterodimeric partner also shared by the hypoxia-inducible factor-1α (HIF-1α) protein. TCDD-stimulated AhR transcriptional activity can be influenced by hypoxia; however, it less well known whether hypoxia interferes with AhR transcriptional transactivation in the context of PCB-mediated AhR activation in human cells. Elucidation of this interaction is important in liver hepatocytes which extensively metabolize ingested PCBs and experience varying degrees of oxygen tension during normal physiologic function. This study was designed to assess the effect of hypoxia on AhR transcriptional responses after exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126). Exposure to 1% O2 prior to PCB 126 treatment significantly inhibited CYP1A1 mRNA and protein expression in human HepG2 and HaCaT cells. CYP1A1 transcriptional activation was significantly decreased upon PCB 126 stimulation under conditions of hypoxia. Additionally, hypoxia pre-treatment reduced PCB 126 induced AhR binding to CYP1 target gene promoters. Importantly, ARNT overexpression rescued cells from the inhibitory effect of hypoxia on XRE-luciferase reporter activity. Therefore, the mechanism of interference of the signaling crosstalk between the AhR and hypoxia pathways appears to be at least in part dependent on ARNT availability. Our results show that AhR activation and CYP1A1 expression induced by PCB 126 were significantly inhibited by hypoxia and hypoxia might therefore play an important role in PCB metabolism and toxicity.
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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.