ArticleFree radical biology & medicine2020
NFκB promotes oxidative stress-induced necrosis and ischemia/reperfusion injury by inhibiting Nrf2-ARE pathway.
Article in Free radical biology & medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Research trends and cellular targets of NF-κB pathway in acute lung injury [2005-2024]: a combined bibliometric analysis and systematic review.Journal of thoracic disease · 2026Article
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Microbiota-Derived Metabolites in the Epigenetic Regulation of Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2026Review
- Qishen Yiqi Dripping Pills Activate HDAC3-Mediated Nrf2-PITX2 Signaling Pathway to Reduce Oxidative Stress and Alleviate Myocardial Infarction Injury in Mice.Chinese journal of integrative medicine · 2026Article
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Microfluidic Modeling of Macrophage-Induced Cardiac Inflammation Using NF-κB Reporter Cardiomyocytes.Advanced healthcare materials · 2026Article
- Genome-Wide Histone Acetylation Underlies Tumor Intrinsic Immune Signaling Induced by Photothermal Therapy in Ovarian Cancer.Research square · 2026Article
- Taxifolin Attenuates Remote Lung Injury Induced by Hepatic Ischemia-Reperfusion in Rats.Molecules (Basel, Switzerland) · 2026Article
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- Acute Myocardial Infarction: Molecular Pathogenesis, Diagnosis, and Clinical Management.MedComm · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- The Inhibition of Prolyl Endopeptidase (PREP) by KYP-2047 Treatment to Reduce Myocardial Ischemia/Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2025Article
- Peptidylarginine deiminase 4 deficiency alleviates hypoxia/reoxygenation-induced cardiomyocyte injury.PloS one · 2025Article
- Review
- Potential Targets of Natural Products for Improving Cardiac Ischemic Injury: The Role of Nrf2 Signaling Transduction.Molecules (Basel, Switzerland) · 2024Review
- Review
- Sustained activation of NF-κB through constitutively active IKKβ leads to senescence bypass in murine dermal fibroblasts.Cell cycle (Georgetown, Tex.) · 2024Article
- The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis.Frontiers in immunology · 2024Review
- Uncoupling Protein 2 Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Cardiomyocyte Ferroptosis.Journal of vascular research · 2024Article
- Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway.Burns & trauma · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
In this study, we identified an unexpected pro-cell death role for NFκB in mediating oxidative stress-induced necrosis, and provide new mechanistic evidence that NFκB, in cooperation with HDAC3, negatively regulates Nrf2-ARE anti-oxidative signaling through transcriptional silencing. We showed that genetic inactivation of NFκB-p65 inhibited, whereas activation of NFκB promoted, oxidative stress-induced cell death and HMGB1 release, a biomarker of necrosis. Moreover, NFκB-luciferase activity was elevated in cardiomyocytes after simulated ischemia/reperfusion (sI/R) or doxorubicin (DOX) treatment, and inhibition of NFκB with Ad-p65-shRNA or Ad-IκBαM diminished sI/R- and DOX-induced cell death and HMGB1 release. Importantly, NFκB negatively regulated Nrf2-ARE activity and the expression of antioxidant proteins. Mechanistically, co-immunoprecipitation revealed that p65 was required for Nrf2-HDAC3 interaction and transcriptional silencing of Nrf2-ARE activity. Further, the ability of HDAC3 to repress Nrf2-ARE activity was lost in p65 deficient cells. Pharmacologic inhibition of HADCs or NFκB with trichostatin A (TSA) or BMS-345541, respectively, increased Nrf2-ARE activity and promoted cell survival after sI/R. In vivo, NFκB transcriptional activity in the mouse heart was significantly elevated after ischemia/reperfusion (I/R) injury, which was abolished by cardiomyocyte-specific deletion of p65 using p65
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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.