ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 43 citations in OpenAlex.
- Exploring the Activation of the Keap1-Nrf2-ARE Pathway by PAHs in Children's Toys.Contact dermatitis · 2025Article
- Redox mechanisms of environmental toxicants on male reproductive function.Frontiers in cell and developmental biology · 2024Review
- Azadirachtin Attenuates Carcinogen Benzo(a) Pyrene-Induced DNA Damage, Cell Cycle Arrest, Apoptosis, Inflammatory, Metabolic, and Oxidative Stress in HepG2 Cells.Antioxidants (Basel, Switzerland) · 2023Article
- Dimethyl Fumarate Attenuates Di-(2-Ethylhexyl) Phthalate-Induced Nephrotoxicity Through the Nrf2/HO-1 and NF-κB Signaling Pathways.Inflammation · 2023Article
- Antioxidant Phytochemicals as Potential Therapy for Diabetic Complications.Antioxidants (Basel, Switzerland) · 2023Review
- Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer.Seminars in cancer biology · 2021Review
- Mechanistic insight into toxicity of phthalates, the involved receptors, and the role of Nrf2, NF-κB, and PI3K/AKT signaling pathways.Environmental science and pollution research international · 2021Review
- Down-Regulation of p23 in Normal Lung Epithelial Cells Reduces Toxicities From Exposure to Benzo[a]pyrene and Cigarette Smoke Condensate via an Aryl Hydrocarbon Receptor-Dependent Mechanism.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[International journal of molecular sciences · 2018Article
- Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4.Scientific reports · 2017Article
- Modulation of Benzo[a]Pyrene Induced Anxiolytic-Like Behavior by Retinoic Acid in Zebrafish: Involvement of Oxidative Stress and Antioxidant Defense System.Neurotoxicity research · 2017Article
- Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor.Biochemical pharmacology · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
We employed the suppressive subtractive hybridization to identify 41 up- and downregulated transcripts in Jurkat cells after benzo[a]pyrene (BaP) treatment. Among the 21 downregulated transcripts, we found that BaP suppresses the Keap1 transcript by 7.5-fold. Subsequent analyses revealed that BaP significantly suppresses the Keap1 message and protein levels to about 40 and 60%, respectively, of the vehicle controls in Jurkat cells without reactive oxygen species involvement. In addition, the nuclear Nrf2 (nuclear factor erythroid 2-related factor) protein content is significantly increased by 2.6-fold. The same BaP treatment to Hepa1c1c7 cells also downregulates the Keap1 message and protein levels to a similar extent. When we treated Jurkat cells with 3-(4-morpholinyl)propyl isothiocyanate, which is known to increase the amount of the Nrf2 content, we found that there is no change in the Keap1 message, but the amount of the Keap1 (kelch-like ECH-associated protein 1) protein is reduced to 75% of the vehicle controls. Although both Nrf2 target messages nqo1 and gstp1 are upregulated by BaP in Jurkat cells, only GSTP1 is upregulated at the protein level. Unlike Hepa1c1c7 cells, Jurkat cells have no detectable aryl hydrocarbon receptor and BaP metabolites, minimal CYP1A1 activity, and no quinone oxidoreductase 1 (NQO1) activity. We concluded that BaP, but not its metabolites, increases the amount of the nuclear Nrf2 protein by downregulating the Keap1 message in Jurkat cells.
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