Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin
| العنوان: | Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin |
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| المؤلفون: | Dirk Werling, Alun Williams |
| المساهمون: | Williams, Alun [0000-0003-0835-0200], Apollo - University of Cambridge Repository |
| المصدر: | BMC Neuroscience, Vol 13, Iss 1, p 106 (2012) BMC Neuroscience |
| بيانات النشر: | BMC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Time Factors, Phospholipases A2, Cytosolic, Synapse, Mice, Phospholipase A2, Tubulin, Drug Interactions, Enzyme Inhibitors, Cytoskeleton, Cells, Cultured, Cerebral Cortex, Neurons, Arachidonic Acid, biology, Cell Death, Chemistry, General Neuroscience, Ionomycin, Neurodegeneration, lcsh:QP351-495, Ketones, Cell biology, Protein Transport, Tetradecanoylphorbol Acetate, lipids (amino acids, peptides, and proteins), Intracellular, Research Article, Neurite, Prions, Synaptophysin, Tritium, PACOCF3, lcsh:RC321-571, Cellular and Molecular Neuroscience, medicine, Neurotoxicity, Animals, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Analysis of Variance, Dose-Response Relationship, Drug, medicine.disease, Embryo, Mammalian, Peptide Fragments, Enzyme Activation, lcsh:Neurophysiology and neuropsychology, Gene Expression Regulation, biology.protein |
| الوصف: | Background Activation of phospholipase A2 (PLA2) and the subsequent metabolism of arachidonic acid (AA) to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Results Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated proteins. Conversely, p-cPLA2 did significantly colocalise with the cytoskeletal protein beta III tubulin. Pre-treatment with the PLA2 inhibitor, palmitoyl trifluoromethyl ketone (PACOCF3) reduced cPLA2 activation, AA release and damage to the neuronal synapse. Furthermore, PACOCF3 reduced expression of p-cPLA2 in neurites and inhibited colocalisation with beta III tubulin, resulting in protection against PrP-induced cell death. Conclusions Collectively, these findings suggest that cPLA2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. Further work is needed to define exactly how PLA2 inhibitors protect neurons from peptide-induced toxicity and how this relates to intracellular structural changes occurring in neurodegeneration. |
| وصف الملف: | text/xml; application/pdf; image/tiff |
| اللغة: | English |
| تدمد: | 1471-2202 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9bd5d5bea60e0331f0cb4a95c3cf7a1Test http://www.biomedcentral.com/1471-2202/13/106Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b9bd5d5bea60e0331f0cb4a95c3cf7a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712202 |
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