The radical scavenger CR-6 protects SH-SY5Y neuroblastoma cells from oxidative stress-induced apoptosis: effect on survival pathways
| العنوان: | The radical scavenger CR-6 protects SH-SY5Y neuroblastoma cells from oxidative stress-induced apoptosis: effect on survival pathways |
|---|---|
| المؤلفون: | Thomas G. Cotter, Violeta Gómez-Vicente, Angel Messeguer, Nuria Sanvicens |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Programmed cell death, Cell Survival, Apoptosis, Therapeutics, Radical scavenger, medicine.disease_cause, Neurodegenerative disease, Biochemistry, Cellular and Molecular Neuroscience, Neuroblastoma, Cell Line, Tumor, medicine, Humans, Benzopyrans, Caspase, chemistry.chemical_classification, Reactive oxygen species, biology, Dose-Response Relationship, Drug, Intrinsic apoptosis, Neurodegeneration, Reactive oxigen species, Calpain, Free Radical Scavengers, Hydrogen Peroxide, medicine.disease, Cell biology, Oxidative Stress, Neuroprotective Agents, chemistry, Oxidative stress, Immunology, biology.protein |
| الوصف: | 13 pages, 4 figures.-- PMID: 16787420 [PubMed]. Reactive oxygen species (ROS) and oxidative stress have long been linked to cell death of neurons in many neurodegenerative conditions. However, the exact molecular mechanisms triggered by oxidative stress in neurodegeneration are at present unclear. In the current work we have used the human neuroblastoma SH-SY5Y cell line as a model for studying the molecular events occurring after inducing apoptosis with H2O2. We show that treatment of SH-SY5Y cells with H2O2 up-regulates survival pathways during early stages of apoptosis. Subsequently, the decline of anti-apoptotic protein levels leads to the activation of the calcium-dependent proteases calpains and the cysteine proteases caspases. Additionally, we demonstrate that CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran) acts as a scavenger of ROS and prevents apoptosis by enhancing and prolonging up-regulation of survival pathways. Furthermore, we show that pre-treatment of SH-SY5Y cells with a cocktail containing CR-6, the pan-caspase inhibitor zVAD-fmk (zVal-Ala-Asp-fluoro-methylketone) and the calpain inhibitor SJA6017 confers almost total protection against apoptosis. In summary, the present work characterizes the molecular mechanisms involved in oxidative stress-induced apoptosis in SH-SY5Y cells. Our findings highlight the relevance of CR-6, alone or in combination with other drugs, as potential therapeutic strategy for the treatment of neurodegenerative diseases. This work was supported by the Health Research Board of Ireland. |
| وصف الملف: | 19968 bytes; application/msword |
| تدمد: | 0022-3042 1678-7420 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b13d27f5a21bf832a12f9b6b1677d21Test https://pubmed.ncbi.nlm.nih.gov/16787420Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4b13d27f5a21bf832a12f9b6b1677d21 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00223042 16787420 |
|---|