ArticleJournal of neuroinflammation2015
NF-κB transcriptional activation by TNFα requires phospholipase C, extracellular signal-regulated kinase 2 and poly(ADP-ribose) polymerase-1.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Preclinical evaluation of puerarin for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- A yeast-derived postbiotic fermentate rapidly modulates inflammatory cytokines and immune surveillance markers in healthy adults: a randomized double-blind placebo-controlled cross-over trial.Frontiers in nutrition · 2026Trial
- Gut microbiome modulation by Veillonella ratti induces resistance to EAE pathogenesis via microbe-derived metabolites.Experimental & molecular medicine · 2026Article
- VEGF inhibitor-induced vascular dysfunction involves redox-sensitive PARP activation and SIRT1 disruption.Experimental physiology · 2026Article
- Acupuncture: A Promising Non-Pharmacological Approach to Parkinson's Disease Management.Brain and behavior · 2026Review
- Exploring the molecular mechanism of apigenin in treating bronchiectasis based on network pharmacology and molecular docking.Scientific reports · 2025Article
- Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP-Ribose) Polymerase Inhibitor Veliparib.Journal of the American Heart Association · 2025Article
- CD133 expression is associated with less DNA repair, better response to chemotherapy and survival in ER-positive/HER2-negative breast cancer.Breast cancer research and treatment · 2024Article
- Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development.Pharmaceutics · 2024Review
- PARP1 as an Epigenetic Modulator: Implications for the Regulation of Host-Viral Dynamics.Pathogens (Basel, Switzerland) · 2024Review
- Store-operated calcium entry in the satellite glial cells of rat sympathetic ganglia.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide.Nature communications · 2023Article
- Activation of Dendritic Cells Isolated from the Blood of Patients with Prostate Cancer by Ex Vivo Fluid Shear Stress Stimulation.Current protocols · 2023Article
- Fluid shear stress enhances dendritic cell activation.Immunobiology · 2023Article
- PARP1 and OGG1 in Medicated Patients With Depression and the Response to ECT.The international journal of neuropsychopharmacology · 2023Article
- KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway.The Journal of cell biology · 2023Article
- Advances in the study of the molecular biological mechanisms of radiation-induced brain injury.American journal of cancer research · 2023Review
- PARP2 downregulation in T cells ameliorates lipopolysaccharide-induced inflammation of the large intestine.Frontiers in immunology · 2023Article
- GPR35 acts a dual role and therapeutic target in inflammation.Frontiers in immunology · 2023Review
- Effects of Corchorusoside C on NF-κB and PARP-1 Molecular Targets and Toxicity Profile in Zebrafish.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) is required for pro-inflammatory effects of TNFα. Our previous studies demonstrated that PARP-1 mediates TNFα-induced NF-κB activation in glia. Here, we evaluated the mechanisms by which TNFα activates PARP-1 and PARP-1 mediates NF-κB activation.
methodsPrimary cultures of mouse cortical astrocytes and microglia were treated with TNFα and suitable signaling pathway modulators (pharmacological and molecular). Outcome measures included calcium imaging, PARP-1 activation status, NF-κB transcriptional activity, DNA damage assesment and cytokine relesease profiling.
resultsTNFα induces PARP-1 activation in the absence of detectable DNA strand breaks, as measured by the PANT assay. TNFα-induced transcriptional activation of NF-κB requires PARP-1 enzymatic activity. Enzymatic activation of PARP-1 by TNFα was blocked in Ca(2+)-free medium, by Ca(2+) chelation with BAPTA-AM, and by D609, an inhibitor of phoshatidyl choline-specific phospholipase C (PC-PLC), but not by thapsigargin or by U73112, an inhibitor of phosphatidyl inisitol-specific PLC (PI -PLC). A TNFR1 blocking antibody reduced Ca(2+) influx and PARP-1 activation. TNFα-induced PARP-1 activation was also blocked by siRNA downregulation of ERK2 and by PD98059, an inhibitor of the MEK / ERK protein kinase cascade. Moreover, TNFα-induced NF-κB (p65) transcriptional activation was absent in cells expressing PARP-1 that lacked ERK2 phosphorylation sites, while basal NF-κB transcriptional activation increased in cells expressing PARP-1 with a phosphomimetic substitution at an ERK2 phophorylation site.
conclusionsThese results suggest that TNFα induces PARP-1 activation through a signaling pathway involving TNFR1, Ca(2+) influx, activation of PC-PLC, and activation of the MEK1 / ERK2 protein kinase cascade. TNFα-induced PARP-1 activation is not associated with DNA damage, but ERK2 mediated phosphorylation of PARP-1.
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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.