ArticleJournal of neuroscience research2008
Manganese potentiates nuclear factor-kappaB-dependent expression of nitric oxide synthase 2 in astrocytes by activating soluble guanylate cyclase and extracellular responsive kinase signaling pathways.
Article in Journal of neuroscience research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- The role of the PM2.5-associated metals in pathogenesis of child Mycoplasma Pneumoniae infections: a systematic review.Environmental science and pollution research international · 2016Pooled it
- The Role and Mechanism of the cGAS-STING/NLRP3 Signaling Axis-Regulated p38 MAPK/NF-κB Pathway in Manganese-Induced Tau Aggregation-Mediated Neurotoxicity.Environment & health (Washington, D.C.) · 2026Article
- Exposure to manganese during juvenile development increases microglial activation in the hippocampus following systemic infection with A/California/04/2009 Influenza A H1N1 virus.Frontiers in toxicology · 2026Article
- Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders.Journal of xenobiotics · 2025Review
- Activation of ERK/NF-kB Pathways Contributes to the Inflammatory Response in Epithelial Cells and Macrophages Following Manganese Exposure.Biological trace element research · 2025Article
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases.Biological trace element research · 2024Review
- Review
- Microglia Signaling Pathway Reporters Unveiled Manganese Activation of the Interferon/STAT1 Pathway and Its Mitigation by Flavonoids.Molecular neurobiology · 2023Article
- Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain.International journal of molecular sciences · 2022Article
- Selenium abates manganese-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats.Psychopharmacology · 2022Article
- Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies.Frontiers in pharmacology · 2022Review
- Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.International journal of molecular sciences · 2021Review
- Article
- Manganese Accumulation in the Brain via Various Transporters and Its Neurotoxicity Mechanisms.Molecules (Basel, Switzerland) · 2020Review
- New Insights on the Role of Manganese in Alzheimer's Disease and Parkinson's Disease.International journal of environmental research and public health · 2019Review
- Genetic suppression of IKK2/NF-κB in astrocytes inhibits neuroinflammation and reduces neuronal loss in the MPTP-Probenecid model of Parkinson's disease.Neurobiology of disease · 2019Article
- Environmental neurotoxicant-induced dopaminergic neurodegeneration: a potential link to impaired neuroinflammatory mechanisms.Pharmacology & therapeutics · 2019Review
- Complex interaction of dietary fat and Alaskan bog blueberry supplementation influences manganese mediated neurotoxicity and behavioral impairments.Journal of functional foods · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory activation of glial cells is associated with neuronal injury in several degenerative movement disorders of the basal ganglia, including manganese neurotoxicity. Manganese (Mn) potentiates the effects of inflammatory cytokines on nuclear factor-kappaB (NF-kappaB)-dependent expression of nitric oxide synthase 2 (NOS2) in astrocytes, but the signaling mechanisms underlying this effect have remained elusive. It was postulated in the present studies that direct stimulation of cGMP synthesis and activation of mitogen-activated protein (MAP) kinase signaling pathways underlies the capacity of Mn to augment NF-kappaB-dependent gene expression in astrocytes. Exposure of primary cortical astrocytes to a low concentration of Mn (10 microM) potentiated expression of NOS2 mRNA and protein along with production of NO in response to interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), which was prevented by overexpression of dominant negative IkappaB alpha. Mn also potentiated IFNgamma- and TNFalpha-induced phosphorylation of extracellular response kinase (ERK), p38, and JNK, as well as cytokine-induced activation of a fluorescent NF-kappaB reporter construct in transgenic astrocytes. Activation of ERK preceded that of NF-kappaB and was required for maximal activation of NO synthesis. Independently of IFNgamma/TNFalpha, Mn-stimulated synthesis of cGMP in astrocytes and inhibition of soluble guanylate cyclase (sGC) abolished the potentiating effect of Mn on MAP kinase phosphorylation, NF-kappaB activation, and production of NO. These data indicate that near-physiological concentrations of Mn potentiate cytokine-induced expression of NOS2 and production of NO in astrocytes via activation of sGC, which promotes ERK-dependent enhancement of NF-kappaB signaling.
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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.