ArticleToxicology and applied pharmacology2009
Disruption of period gene expression alters the inductive effects of dioxin on the AhR signaling pathway in the mouse liver.
Article in Toxicology and applied pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 42 citations in OpenAlex.
- Aryl hydrocarbon receptor activation alters emergency hematopoiesis during influenza A virus infection.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Review
- Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling.The European journal of neuroscience · 2020Article
- Role of Aryl Hydrocarbon Receptor in Circadian Clock Disruption and Metabolic Dysfunction.Environmental health insights · 2016Review
- Article
- Interplay between Dioxin-mediated signaling and circadian clock: a possible determinant in metabolic homeostasis.International journal of molecular sciences · 2014Review
- Chronopharmacology: new insights and therapeutic implications.Annual review of pharmacology and toxicology · 2014Review
- Sex differences in the circadian variation of cytochrome p450 genes and corresponding nuclear receptors in mouse liver.Chronobiology international · 2013Article
- Circadian rhythm disruption in cancer biology.Molecular medicine (Cambridge, Mass.) · 2012Review
- The mammalian circadian system is resistant to dioxin.Journal of biological rhythms · 2012Article
- Circadian clock disruption in the mouse ovary in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Toxicology letters · 2011Article
- The clock genes period 1 and period 2 mediate diurnal rhythms in dioxin-induced Cyp1A1 expression in the mouse mammary gland and liver.Toxicology letters · 2010Article
- Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) are transcription factors that express Per-Arnt-Sim (PAS) DNA-binding motifs and mediate the metabolism of drugs and environmental toxins in the liver. Because these transcription factors interact with other PAS genes in molecular feedback loops forming the mammalian circadian clockworks, we determined whether targeted disruption or siRNA inhibition of Per1 and Per2 expression alters toxin-mediated regulation of the AhR signaling pathway in the mouse liver and Hepa1c1c7 hepatoma cells in vitro. Treatment with the prototypical Ahr ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), had inductive effects on the primary targets of AhR signaling, Cyp1A1 and Cyp1B1, in the liver of all animals, but genotype-based differences were evident such that the toxin-mediated induction of Cyp1A1 expression was significantly greater (2-fold) in mice with targeted disruption of Per1 (Per1(ldc) and Per1(ldc)/Per2(ldc)). In vitro experiments yielded similar results demonstrating that siRNA inhibition of Per1 significantly increases the TCDD-induced expression of Cyp1A1 and Cyp1B1 in Hepa1c1c7 cells. Per2 inhibition in siRNA-infected Hepa1c1c7 cells had the opposite effect and significantly decreased both the induction of these p450 genes as well as AhR and Arnt expression in response to TCDD treatment. These findings suggest that Per1 may play a distinctive role in modulating AhR-regulated responses to TCDD in the liver.
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