STI571 protects neuronal cells from neurotoxic prion protein fragment-induced apoptosis
| Autor: | Jin Wang, Yigang Tong, Liyong Sun, Jihong Wang, Bo Pan, Yongyao Fu, Wenzhuo Fu, Yaoqian Pan |
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| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Prions animal diseases Apoptosis Scrapie Biology Mitochondrion Mice Neuroblastoma Cellular and Molecular Neuroscience Microscopy Electron Transmission Cell Line Tumor Proto-Oncogene Proteins In Situ Nick-End Labeling medicine Animals RNA Messenger Pharmacology Bcl-2-Like Protein 11 Dose-Response Relationship Drug Cytochrome c Neurodegeneration Neurotoxicity Membrane Proteins Membrane Transport Proteins medicine.disease Peptide Fragments Mitochondria nervous system diseases Cell biology Gene Expression Regulation Neoplastic Neuroprotective Agents Imatinib mesylate Caspases Immunology Imatinib Mesylate biology.protein Apoptosis Regulatory Proteins Reactive Oxygen Species Tyrosine kinase |
| Zdroj: | Neuropharmacology. 93:191-198 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2015.01.029 |
| Popis: | Prion diseases are neurodegenerative disorders caused by the accumulation of misfolded prion proteins [scrapie form of PrP (PrP(Sc))]. PrP(Sc) accumulation in the brain causes neurotoxicity by inducing mitochondrial-apoptotic pathways. Neurodegeneration can be prevented by imatinib mesylate (Gleevec or STI571) that regulates c-Abl tyrosine kinases, which elicit protective effects in neurodegenerative disease models. However, the protective effect of STI571 against prion disease remains unknown. In the present study, the effect of STI571 on prion peptide-induced neuronal death was investigated. Results showed that STI571 rescued neurons from PrP106-126-induced neurotoxicity by preventing mitochondrial dysfunction. STI571-inhibited c-Abl tyrosine kinases prevented PrP106-126-induced reduction in mitochondrial potential, Bax translocation to the mitochondria and cytochrome c release. The protective effect of STI571 against mitochondrial dysfunction was related to the activation of BIM expression. This study is the first to demonstrate the protective effect of STI571 against prion-mediated neurotoxicity. Our results suggested that imatinib mesylate treatment may be a novel therapeutic strategy to treat prion-mediated neurotoxicity. |
| Databáze: | OpenAIRE |
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