ArticleAntioxidants & redox signaling2015
Frequency Modulated Translocational Oscillations of Nrf2 Mediate the Antioxidant Response Element Cytoprotective Transcriptional Response.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Effect of Running Exercise on Oxidative Stress Biomarkers: A Systematic Review.Frontiers in physiology · 2020Pooled it
- Trial
- Epiregulin Mitigates Type 2 Diabetes-associated Cognitive Dysfunction by Inhibiting Hippocampal Neuronal Ferroptosis via the Nrf2 Pathway.Molecular neurobiology · 2026Article
- The oxidative stress-inflammation self-perpetuating cycle in multiple sclerosis: from mechanisms to emerging antioxidant strategies.Frontiers in pharmacology · 2026Review
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Review
- Overload of Glucose Metabolism as Initiating Factor in Diabetic Embryopathy and Prevention by Glyoxalase 1 Inducer Dietary Supplement.Antioxidants (Basel, Switzerland) · 2025Article
- Glyoxalase 1 Inducer,Antioxidants (Basel, Switzerland) · 2025Article
- Anti-osteoporosis activity of casticin in ovariectomized rats.Toxicology research · 2024Article
- 3D human stem-cell-derived neuronal spheroids forCurrent research in toxicology · 2024Article
- Nrf2 modulates the benefits of evening exercise in type 2 diabetes.Sports medicine and health science · 2023Review
- Administration of Akebia Saponin D Improved Blood Lipid Levels and Pregnancy Outcomes in Mice with Gestational Diabetes MellitusBalkan medical journal · 2023Article
- The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues.International journal of molecular sciences · 2023Review
- Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.Frontiers in endocrinology · 2023Article
- Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro.International journal of nanomedicine · 2023Article
- Isoorientin ameliorates osteoporosis and oxidative stress in postmenopausal rats.Pharmaceutical biology · 2022Article
- The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications.The Biochemical journal · 2022Review
- Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.Redox biology · 2022Review
- Emerging Glycation-Based Therapeutics-Glyoxalase 1 Inducers and Glyoxalase 1 Inhibitors.International journal of molecular sciences · 2022Review
- Hexokinase-2-Linked Glycolytic Overload and Unscheduled Glycolysis-Driver of Insulin Resistance and Development of Vascular Complications of Diabetes.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsStress responsive signaling coordinated by nuclear factor erythroid 2-related factor 2 (Nrf2) provides an adaptive response for protection of cells against toxic insults, oxidative stress and metabolic dysfunction. Nrf2 regulates a battery of protective genes by binding to regulatory antioxidant response elements (AREs). The aim of this study was to examine how Nrf2 signals cell stress status and regulates transcription to maintain homeostasis.
resultsIn live cell microscopy we observed that Nrf2 undergoes autonomous translocational frequency-modulated oscillations between cytoplasm and nucleus. Oscillations occurred in quiescence and when cells were stimulated at physiological levels of activators, they decrease in period and amplitude and then evoke a cytoprotective transcriptional response. We propose a mechanism whereby oscillations are produced by negative feedback involving successive de-phosphorylation and phosphorylation steps. Nrf2 was inactivated in the nucleus and reactivated on return to the cytoplasm. Increased frequency of Nrf2 on return to the cytoplasm with increased reactivation or refresh-rate under stress conditions activated the transcriptional response mediating cytoprotective effects. The serine/threonine-protein phosphatase PGAM5, member of the Nrf2 interactome, was a key regulatory component. INNOVATION: We found that Nrf2 is activated in cells without change in total cellular Nrf2 protein concentration. Regulation of ARE-linked protective gene transcription occurs rather through translocational oscillations of Nrf2. We discovered cytoplasmic refresh rate of Nrf2 is important in maintaining and regulating the transcriptional response and links stress challenge to increased cytoplasmic surveillance. We found silencing and inhibition of PGAM5 provides potent activation of Nrf2.
conclusionFrequency modulated translocational oscillations of Nrf2 mediate the ARE-linked cytoprotective transcriptional response.
Indexed as
Identifiers
What OpenQuestion holds
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.