ArticlePloS one2012
Suppression of the Nrf2-dependent antioxidant response by glucocorticoids and 11β-HSD1-mediated glucocorticoid activation in hepatic cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 91 citations in OpenAlex.
- Dystrophin Deficiency Creates a Pro-Ferroptotic Environment in Diaphragm of mdx Mice That Is Modified by Diet and Glucocorticoid Treatment.Biomolecules · 2026Article
- Sex-specific mitochondrial dysregulation and metformin response in Wilson disease.Scientific reports · 2026Article
- Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis.Clinical and experimental otorhinolaryngology · 2026Review
- Hierarchical Mechanistic Modeling of Complex Toxicity Endpoints from Public Concentration-Response Data.Environmental science & technology · 2026Article
- Molecular pathways linking chronic psychological stress to accelerated aging: mechanisms and interventions.Frontiers in aging · 2026Review
- Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency.Redox biology · 2025Article
- The Antioxidant Effect of Selenium Is Enhanced by Cortisol Through Nrf2 Pathway in Bovine Endometrial Epithelial Cells.Animals : an open access journal from MDPI · 2025Article
- NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells.International journal of molecular sciences · 2024Article
- Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure inAntioxidants (Basel, Switzerland) · 2024Article
- Selenium suppressed the LPS-induced oxidative stress of bovine endometrial stromal cells through Nrf2 pathway with high cortisol background.Journal of animal science · 2024Article
- Endogenous and exogenous protection from surgically induced reactive oxygen and nitrogen species.Surgery today · 2024Review
- Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.Journal of neuroinflammation · 2023Article
- Molecular Hydrogen Prevents Osteoclast Activation in a Glucocorticoid-Induced Osteoporosis Zebrafish Scale Model.Antioxidants (Basel, Switzerland) · 2023Article
- Prolonged maternal exposure to glucocorticoids alters selenoprotein expression in the developing brain.Frontiers in molecular neuroscience · 2023Article
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor.Frontiers in pharmacology · 2022Article
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Peroxiredoxin 6 Knockout Mice Demonstrate Anxiety Behavior and Attenuated Contextual Fear Memory after Receiving Acute Immobilization Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Superoxide dismutase (SOD), advanced oxidation protein products (AOPP), and disease-modifying treatment are related to better relapse recovery after corticosteroid treatment in multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Article
- Perspectives on the Clinical Development of NRF2-Targeting Drugs.Handbook of experimental pharmacology · 2021Review
- Stress and the Brain: An Emerging Role for Selenium.Frontiers in neuroscience · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key transcription factor regulating a plethora of detoxifying enzymes and antioxidant genes involved in drug metabolism and defence against oxidative stress. The glucocorticoid receptor (GR) is a ligand-induced transcription factor involved in the regulation of energy supply for metabolic needs to cope with various stressors. GR activity is controlled by glucocorticoids, which are synthesized in the adrenal glands and regenerated mainly in the liver from inactive cortisone by 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1). METHODS AND PRINCIPAL
findingsUsing transfected HEK-293 cells and hepatic H4IIE cells we show that glucocorticoids, activated by 11β-HSD1 and acting through GR, suppress the Nrf2-dependent antioxidant response. The expression of the marker genes NQO1, HMOX1 and GST2A was suppressed upon treatment of 11β-HSD1 expressing cells with cortisone, an effect that was reversed by 11β-HSD1 inhibitors. Furthermore, our results demonstrate that elevated glucocorticoids lowered the ability of cells to detoxify H(2)O(2). Moreover, a comparison of gene expression in male and female rats revealed an opposite sexual dimorphism with an inverse relationship between 11β-HSD1 and Nrf2 target gene expression.
conclusionsThe results demonstrate a suppression of the cellular antioxidant defence capacity by glucocorticoids and suggest that elevated 11β-HSD1 activity may lead to impaired Nrf2-dependent antioxidant response. The gender-specific differences in hepatic expression levels of 11β-HSD1 and Nrf2 target genes and the impact of pharmacological inhibition of 11β-HSD1 on improving cellular capacity to cope with oxidative stress warrants further studies in vivo.
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