ReviewAntioxidants (Basel, Switzerland)2019
Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR).
Review in Antioxidants (Basel, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- Melatonin reprograms antioxidant defenses to suppress ferroptosis via Homer1a/mGluR1-Nrf2/xCT signaling after retinal ischemia-reperfusion.Redox biology · 2026Article
- [Research Advances in the Pulmonary Carcinogenic Effects of Atmospheric Fine Particulate Matter Mediated by GPER].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Sex-based differences in the NRF2 oxidative stress response: Implications for precision therapeutics.Redox biology · 2026Review
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- Oxidative Stress and the KEAP1/NRF2 Axis in Saphenous Vein: Implications for Graft Patency.Cells · 2026Review
- The estrogen-ferroptosis axis in postmenopausal osteoporosis, osteoarthritis, and intervertebral disc degeneration: shared mechanisms and emerging evidence.Frontiers in immunology · 2026Review
- Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025Review
- Sex-specific glomerular filtration rate changes in response to acute hemoglobin exposure.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Fumarate Signaling in Cardiovascular Disease: Therapeutic Potential and Pathologic Pitfalls of DMF/MMF and FH1 Deficiency.Journal of cardiovascular translational research · 2025Review
- GPER in metabolic homeostasis and disease: molecular mechanisms, nutritional regulation, and therapeutic potential.Journal of translational medicine · 2025Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- Identification of Food-Derived Electrophilic Chalcones as Nrf2 Activators Using Comprehensive Virtual Screening Techniques.Antioxidants (Basel, Switzerland) · 2025Article
- G-Protein-Coupled Estrogen Receptor 1 (GPER1) Activation Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Improves Motor Functions in Adult Zebrafish.Neurochemical research · 2025Article
- Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease.Cell death & disease · 2025Article
- The estrogen-brain interface in neuroinflammation: a multidimensional mechanistic insight.Frontiers in aging neuroscience · 2025Review
- Association Between Serum G Protein-Coupled Estrogen Receptor and the Peripheral Blood Balance of T-Helper/New Effector T-Cells in Patients With Hashimoto's Thyroiditis.International journal of endocrinology · 2025Article
- ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell.Frontiers in endocrinology · 2025Article
- Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review.Nutrients · 2024Review
- Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Loss of WDR23 proteostasis impacts mitochondrial homeostasis in the mouse brain.Cellular signalling · 2024Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Membrane-associated estrogen receptors (ER)-α36 and G protein-coupled estrogen receptor (GPER) play important roles in the estrogen's rapid non-genomic actions including stimulation of cell proliferation. Estrogen via these receptors induces rapid activation of transcription factor nuclear factor-E2-related factor 2 (Nrf2), a master regulator of detoxification and antioxidant systems, playing a key role in the metabolic reprogramming to support cell proliferation. This review highlights the possible mechanism underlying rapid Nrf2 activation via membrane-associated estrogen receptors by estrogen and phytoestrogens. Stimulation of ER-α36-GPER signaling complex rapidly induces Src-mediated transactivation of epidermal growth factor receptor (EGFR) leading to a kinase-mediated signaling cascade. We propose a novel hypothesis that ER-α36-GPER signaling initially induces rapid and temporal activation of NADPH oxidase 1 to generate superoxide, which subsequently activates redox-sensitive neutral sphingomyelinase 2 generating the lipid signaling mediator ceramide. Generation of ceramide is required for Ras activation and ceramide-protein kinase C ζ-casein kinase 2 (CK2) signaling. Notably, CK2 enhances chaperone activity of the Cdc37-Hsp90 complex supporting activation of various signaling kinases including Src, Raf and Akt (protein kinase B). Activation of Nrf2 may be induced by cooperation of two signaling pathways, (i) Nrf2 stabilization by direct phosphorylation by CK2 and (ii) EGFR-Ras-PI 3 kinase (PI3K)-Akt axis which inhibits glycogen synthase kinase 3β leading to enhanced nuclear transport and stability of Nrf2.
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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.