ArticleEnvironmental health perspectives2012
Profiling environmental chemicals for activity in the antioxidant response element signaling pathway using a high throughput screening approach.
Article in Environmental health perspectives, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
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- Use of Tox21 screening data to profile PFAS bioactivities on nuclear receptors, cellular stress pathways, and cytochrome p450 enzymes.Journal of hazardous materials · 2024Article
- Effects of Chemicals in Reporter Gene Bioassays with Different Metabolic Activities Compared to Baseline Toxicity.Chemical research in toxicology · 2024Article
- Mechanism-driven modeling of chemical hepatotoxicity using structural alerts and an in vitro screening assay.Journal of hazardous materials · 2022Article
- Cell-Based Assays to Identify Modulators of Nrf2/ARE Pathway.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- Application of In Vitro Metabolism Activation in High-Throughput Screening.International journal of molecular sciences · 2020Review
- Nrf2 in liver toxicology.Archives of pharmacal research · 2020Review
- Antioxidant response elements: Discovery, classes, regulation and potential applications.Redox biology · 2018Review
- Channel Interactions and Robust Inference for Ratiometric β-lactamase Assay Data: a Tox21 Library Analysis.ACS sustainable chemistry & engineering · 2018Article
- Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells.Journal of proteome research · 2018Article
- Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity.Journal of environmental sciences (China) · 2017Article
- Low-dose dose-response for reduced cell viability after exposure of human keratinocyte (HEK001) cells to arsenite.Toxicology reports · 2017Article
- Effects of multi-component mixtures of polyaromatic hydrocarbons and heavy metal/loid(s) on Nrf2-antioxidant response element (ARE) pathway in ARE reporter-HepG2 cells.Toxicology research · 2016Article
- High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress.Stem cells translational medicine · 2016Article
- Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.Environmental health perspectives · 2016Article
- Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization.Nature communications · 2016Article
- Cell-Based Assay for Identifying the Modulators of Antioxidant Response Element Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Improving the human hazard characterization of chemicals: a Tox21 update.Environmental health perspectives · 2013Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOxidative stress has been implicated in the pathogenesis of a variety of diseases ranging from cancer to neurodegeneration, highlighting the need to identify chemicals that can induce this effect. The antioxidant response element (ARE) signaling pathway plays an important role in the amelioration of oxidative stress. Thus, assays that detect the up-regulation of this pathway could be useful for identifying chemicals that induce oxidative stress.
objectivesWe used cell-based reporter methods and informatics tools to efficiently screen a large collection of environmental chemicals and identify compounds that induce oxidative stress.
methodsWe utilized two cell-based ARE assay reporters, β-lactamase and luciferase, to screen a U.S. National Toxicology Program 1,408-compound library (NTP 1408, which contains 1,340 unique compounds) for their ability to induce oxidative stress in HepG2 cells using quantitative high throughput screening (qHTS).
resultsRoughly 3% (34 of 1,340) of the unique compounds demonstrated activity across both cell-based assays. Based on biological activity and structure-activity relationship profiles, we selected 50 compounds for retesting in the two ARE assays and in an additional follow-up assay that employed a mutated ARE linked to β-lactamase. Using this strategy, we identified 30 compounds that demonstrated activity in the ARE-bla and ARE-luc assays and were able to determine structural features conferring compound activity across assays.
conclusionsOur results support the robustness of using two different cell-based approaches for identifying compounds that induce ARE signaling. Together, these methods are useful for prioritizing chemicals for further in-depth mechanism-based toxicity testing.
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Registered trials
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.