ArticleChemical research in toxicology2017
Aldo-Keto Reductase Regulation by the Nrf2 System: Implications for Stress Response, Chemotherapy Drug Resistance, and Carcinogenesis.
Article in Chemical research in toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 97 citations in OpenAlex.
- Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response.Particle and fibre toxicology · 2023Trial
- Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition.Frontiers in cell and developmental biology · 2026Review
- Aldose Reductase Involvement in EMT: Emerging Insights and Current Proposed Molecular Mechanisms.Biology · 2025Review
- Multi-omics and Mendelian randomization study explores potential therapeutic targets for meningiomas.Discover oncology · 2025Article
- Natural plant-derived nanovesicles for effective psoriasis therapy via dual modulation of IL-17 and NRF2 pathway.iScience · 2025Article
- Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway.Cell chemical biology · 2025Article
- Next generation thiazolyl ketone inhibitors of cytosolic phospholipase ANature communications · 2025Article
- Mapping the functional network of human cancer through machine learning and pan-cancer proteogenomics.Nature cancer · 2025Article
- Article
- Splicing junction-based classifier for the detection of abnormal constitutive activation of the KEAP1-NRF2 system.NPJ systems biology and applications · 2024Article
- AKR1C1 interacts with STAT3 to increase intracellular glutathione and confers resistance to oxaliplatin in colorectal cancer.Acta pharmaceutica Sinica. B · 2024Article
- Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting.Scientific reports · 2024Article
- Analysis of Expression and Regulation of AKR1C2 in HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.Cancers · 2024Article
- Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.Environmental health : a global access science source · 2024Article
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Aldo-keto reductases: Role in cancer development and theranostics.Oncology research · 2024Review
- Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction.Scientific reports · 2023Article
- Sedanolide Activates KEAP1-NRF2 Pathway and Ameliorates Hydrogen Peroxide-Induced Apoptotic Cell Death.International journal of molecular sciences · 2023Article
- AKR1C1 Protects Corneal Epithelial Cells Against Oxidative Stress-Mediated Ferroptosis in Dry Eye.Investigative ophthalmology & visual science · 2022Article
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1 author at 1 institution in 1 country.
Funding
Abstract
Human aldo-keto reductases (AKRs) are NAD(P)H-dependent oxidoreductases that convert aldehydes and ketones to primary and secondary alcohols for subsequent conjugation reactions and can be referred to as "phase 1" enzymes. Among all the human genes regulated by the Keap1/Nrf2 pathway, they are consistently the most overexpressed in response to Nrf2 activators. Although these enzymes play clear cytoprotective roles and deal effectively with carbonyl stress, their upregulation by the Keap1/Nrf2 pathway also has a potential dark-side, which can lead to chemotherapeutic drug resistance and the metabolic activation of lung carcinogens (e.g., polycyclic aromatic hydrocarbons). They also play determinant roles in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone metabolism to R- and S-4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol. The overexpression of AKR genes as components of the "smoking gene" battery raises the issue as to whether this is part of a smoking stress response or acquired susceptibility to lung cancer. Human AKR genes also regulate retinoid, prostaglandin, and steroid hormone metabolism and can regulate the local concentrations of ligands available for nuclear receptors (NRs). The prospect exists that signaling through the Keap1/Nrf2 system can also effect NR signaling, but this has remained largely unexplored. We present the case that chemoprevention through the Keap1/Nrf2 system may be context dependent and that the Nrf2 "dose-response curve" for electrophilic and redox balance may not be monotonic.
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