ArticleToxicological sciences : an official journal of the Society of Toxicology2013
2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 100 citations in OpenAlex.
- Single-cell analysis of 2,3,7,8-tetrachlorodibenzo-bioRxiv : the preprint server for biology · 2026Article
- Comparative 28-day mouse study of topically applied aryl hydrocarbon receptor ligands: microbiota-derived indoles, therapeutic tapinarof, pollutants 2,3,7,8-tetrachlorodibenzo-p-dioxin and diesel exhaust particles.Chemico-biological interactions · 2026Article
- CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.Nature biotechnology · 2025Article
- Atopic dermatitis-related anti-inflammatory in vitro effects of a plant extract mixture.Scientific reports · 2025Article
- Environmental Toxins and Oxidative Stress: The Link to Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Crosstalk of MAP3K1 and EGFR signaling mediates gene-environment interactions that block developmental tissue closure.The Journal of biological chemistry · 2024Article
- The Antioxidant PAPLAL Protects against Allergic Contact Dermatitis in Experimental Models.Antioxidants (Basel, Switzerland) · 2024Article
- Aryl hydrocarbon receptor role in chronic inflammatory skin diseases: a narrative review.Postepy dermatologii i alergologii · 2024Review
- Aryl hydrocarbon receptor and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis.Frontiers in allergy · 2024Article
- Environmental pro-oxidants induce altered envelope protein profiles in human keratinocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Ligand Activation of the Aryl Hydrocarbon Receptor Upregulates Epidermal Uridine Diphosphate Glucose Ceramide Glucosyltransferase and Glucosylceramides.The Journal of investigative dermatology · 2023Article
- Environmental Air Pollutants Affecting Skin Functions with Systemic Implications.International journal of molecular sciences · 2023Review
- Tryptophan, an important link in regulating the complex network of skin immunology response in atopic dermatitis.Frontiers in immunology · 2023Review
- Transcriptomic Analysis of Human Keratinocytes Treated withJournal of clinical medicine · 2022Article
- Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins.International journal of molecular sciences · 2022Article
- AHR and NRF2 in Skin Homeostasis and Atopic Dermatitis.Antioxidants (Basel, Switzerland) · 2022Review
- Effects of Autophagy Modulators and Dioxin on the Expression of Epidermal Differentiation Proteins on Psoriasis-Like Keratinocytes in vitro and ex vivo.Clinical, cosmetic and investigational dermatology · 2022Article
- Review
- Review
- Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile.International journal of molecular sciences · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Chloracne is commonly observed in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); yet, the mechanism of toxicity is not well understood. Using normal human epidermal keratinocytes, we investigated the mechanism of TCDD-mediated enhancement of epidermal differentiation by integrating functional genomic, metabolomic, and biochemical analyses. TCDD increased the expression of 40% of the genes of the epidermal differentiation complex found on chromosome 1q21 and 75% of the genes required for de novo ceramide biosynthesis. Lipid analysis demonstrated that eight of the nine classes of ceramides were increased by TCDD, altering the ratio of ceramides to free fatty acids. TCDD decreased the expression of the glucose transporter, SLC2A1, and most of the glycolytic transcripts, followed by decreases in glycolytic intermediates, including pyruvate. NADH and Krebs cycle intermediates were decreased, whereas NAD(+) was increased. Mitochondrial glutathione (GSH) reductase activity and the GSH/glutathione disulfide ratio were decreased by TCDD, ultimately leading to mitochondrial dysfunction, characterized by decreased inner mitochondrial membrane potential and ATP production, and increased production of the reactive oxygen species (ROS), hydrogen peroxide. Aryl hydrocarbon receptor (AHR) antagonists blocked the response of many transcripts to TCDD, and the endpoints of decreased ATP production and differentiation, suggesting regulation by the AHR. Cotreatment of cells with chemical antioxidants or the enzyme catalase blocked the TCDD-mediated acceleration of keratinocyte cornified envelope formation, an endpoint of terminal differentiation. Thus, TCDD-mediated ROS production is a critical step in the mechanism of this chemical to accelerate keratinocyte differentiation.
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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.