ArticleNeurotoxicology2011
Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKCδ-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model.
Article in Neurotoxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- High glucose levels sensitize neuron-like cells to damage induced by oxidative and neurotoxic agents.Scientific reports · 2026Article
- Mitochondrial stress disassembles nuclear architecture through proteolytic activation of PKCδ and Lamin B1 phosphorylation in neuronal cells: implications for pathogenesis of age-related neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Article
- Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation.Disease models & mechanisms · 2024Article
- The underlying molecular mechanisms of Fyn in neonatal hypoxic-ischaemic encephalopathy.Frontiers in cellular neuroscience · 2024Review
- Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity.Molecular and cellular biochemistry · 2022Review
- Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson's Disease.International journal of molecular sciences · 2022Review
- Fyn kinase regulates dopaminergic neuronal apoptosis in animal and cell models of high glucose (HG) treatment.BMC molecular and cell biology · 2021Article
- Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: a Potential Universal Target?Molecular neurobiology · 2021Review
- Mitochondrial dysfunction-induced H3K27 hyperacetylation perturbs enhancers in Parkinson's disease.JCI insight · 2021Article
- Pivotal Role of Fyn Kinase in Parkinson's Disease and Levodopa-Induced Dyskinesia: a Novel Therapeutic Target?Molecular neurobiology · 2021Review
- Tyrosine kinase Fyn promotes apoptosis after intracerebral hemorrhage in rats by activating Drp1 signaling.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Fyn Kinase-Mediated PKCδ Y311 Phosphorylation Induces Dopaminergic Degeneration in Cell Culture and Animal Models: Implications for the Identification of a New Pharmacological Target for Parkinson's Disease.Frontiers in pharmacology · 2021Article
- Fyn kinase mediates pro-inflammatory response in a mouse model of endotoxemia: Relevance to translational research.European journal of pharmacology · 2020Article
- Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury.Biomolecules & therapeutics · 2020Review
- Role of the Fyn-PKCδ signaling in SE-induced neuroinflammation and epileptogenesis in experimental models of temporal lobe epilepsy.Neurobiology of disease · 2018Article
- Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance.Frontiers in genetics · 2018Article
- Protein kinase Cδ upregulation in microglia drives neuroinflammatory responses and dopaminergic neurodegeneration in experimental models of Parkinson's disease.Neurobiology of disease · 2016Article
- Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury.The Journal of pharmacology and experimental therapeutics · 2015Article
- Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Essential role of PH domain and leucine-rich repeat protein phosphatase 2 in Nrf2 suppression via modulation of Akt/GSK3β/Fyn kinase axis during oxidative hepatocellular toxicity.Cell death & disease · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress and apoptosis are two key pathophysiological mechanisms underlying dopaminergic degeneration in Parkinson's disease (PD). Recently, we identified that proteolytic activation of protein kinase C-delta (PKCδ), a member of the novel PKC family, contributes to oxidative stress-induced dopaminergic degeneration and that phosphorylation of tyrosine residue 311 (tyr311) on PKCδ is a key event preceding the PKCδ proteolytic activation during oxidative damage. Herein, we report that a non-receptor tyrosine kinase Fyn is significantly expressed in a dopaminergic neuronal N27 cell model. Exposure of N27 cells to the dopaminergic toxicant dieldrin (60 μM) rapidly activated Fyn kinase, PKCδ-tyr311 phosphorylation and proteolytic cleavage. Fyn kinase activation precedes the caspase-3-mediated proteolytic activation of PKCδ. Pre-treatment with p60-tyrosine-specific kinase inhibitor (TSKI) almost completely attenuated dieldrin-induced phosphorylation of PKCδ-tyr311 and its proteolytic activation. Additionally, TSKI almost completely blocked dieldrin-induced apoptotic cell death. To further confirm Fyn's role in the pro-apoptotic function of PKCδ, we adopted the RNAi approach. siRNA-mediated knockdown of Fyn kinase also effectively attenuated dieldrin-induced phosphorylation of PKCδ-tyr311, caspase-3-mediated PKCδ proteolytic cleavage, and DNA fragmentation, suggesting that Fyn kinase regulates the pro-apoptotic function of PKCδ. Collectively, these results demonstrate for the first time that Fyn kinase is a pro-apoptotic kinase that regulates upstream signaling of the PKCδ-mediated apoptotic cell death pathway in neurotoxicity models of pesticide exposure.
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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.