ArticleRedox biology2016
A biphasic effect of TNF-α in regulation of the Keap1/Nrf2 pathway in cardiomyocytes.
Article in Redox biology, 2016. 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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Who cites it
41 citing papers in PubMed, 90 citations in OpenAlex.
- PD-1/PD-L1 Signaling in Non-ICI Myocarditis.JACC. Basic to translational science · 2026Article
- Microfluidic Modeling of Macrophage-Induced Cardiac Inflammation Using NF-κB Reporter Cardiomyocytes.Advanced healthcare materials · 2026Article
- Nuclear factor erythroid 2 related factor 2, tumor necrosis factor alpha, interleukin-40, and endorepellin levels in patients undergoing coronary artery bypass grafting.Revista da Associacao Medica Brasileira (1992) · 2026Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Identifying potential drugs for treating Cardiovascular-kidney metabolic syndrome via reverse network pharmacology.Frontiers in pharmacology · 2025Article
- RvD2 mitigates TNFɑ-Induced mitochondrial reactive oxygen species through NRF2 signaling in placental trophoblasts.Frontiers in physiology · 2025Article
- Neuroprotection of Human Umbilical Cord-Derived Mesenchymal Stem Cells (hUC-MSCs) in Alleviating Ischemic Stroke-Induced Brain Injury by Regulating Inflammation and Oxidative Stress.Neurochemical research · 2024Article
- Acute and Post-Acute COVID-19 Cardiovascular Complications: A Comprehensive Review.Cardiovascular drugs and therapy · 2024Review
- Ameliorating effects ofFood science & nutrition · 2024Article
- LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.Cardiovascular research · 2024Article
- Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.Aging medicine (Milton (N.S.W)) · 2024Article
- HCV-induced autophagy and innate immunity.Frontiers in immunology · 2024Review
- Article
- Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements-A Focused Review.Molecules (Basel, Switzerland) · 2022Review
- Independent Association of Thyroid Dysfunction and Inflammation Predicts Adverse Events in Patients with Heart Failure via Promoting Cell Death.Journal of cardiovascular development and disease · 2022Article
- Novel Insights into the Cardioprotective Effects of Calcitriol in Myocardial Infarction.Cells · 2022Article
- Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host's Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19.International journal of molecular sciences · 2021Review
- COVID-19 and cardiovascular diseases.Journal of molecular cell biology · 2021Review
- Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.The Journal of experimental medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Antagonizing TNF-α signaling attenuates chronic inflammatory disease, but is associated with adverse effects on the cardiovascular system. Therefore the impact of TNF-α on basal control of redox signaling events needs to be understand in more depth. This is particularly important for the Keap1/Nrf2 pathway in the heart and in the present study we hypothesized that inhibition of a low level of TNF-α signaling attenuates the TNF-α dependent activation of this cytoprotective pathway. HL-1 cardiomyocytes and TNF receptor1/2 (TNFR1/2) double knockout mice (DKO) were used as experimental models. TNF-α (2-5ng/ml, for 2h) evoked significant nuclear translocation of Nrf2 with increased DNA/promoter binding and transactivation of Nrf2 targets. Additionally, this was associated with a 1.5 fold increase in intracellular glutathione (GSH). Higher concentrations of TNF-α (>10-50ng/ml) were markedly suppressive of the Keap1/Nrf2 response and associated with cardiomyocyte death marked by an increase in cleavage of caspase-3 and PARP. In vivo experiments with TNFR1/2-DKO demonstrates that the expression of Nrf2-regulated proteins (NQO1, HO-1, G6PD) were significantly downregulated in hearts of the DKO when compared to WT mice indicating a weakened antioxidant system under basal conditions. Overall, these results indicate that TNF-α exposure has a bimodal effect on the Keap1/Nrf2 system and while an intense inflammatory activation suppresses expression of antioxidant proteins a low level appears to be protective.
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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.