| Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells. | |
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MedLine Citation:
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PMID: 10671549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitric oxide (NO) challenge to human neuroblastoma cells (SH-SY5Y) ultimately results in apoptosis. Tumor suppressor protein p53 and cell cycle inhibitor p21 accumulate as an early sign of S-nitrosoglutathione-mediated toxicity. Cytochrome c release from mitochondria and caspase 3 activation also occurred. Cells transfected with either wild type (WT) or mutant (G93A) Cu, Zn-superoxide dismutase (Cu,Zn-SOD) produced comparable amounts of nitrite/nitrate but showed different degree of apoptosis. G93A cells were the most affected and WT cells the most protected; however, Cu, Zn-SOD content of these two cell lines was 2-fold the SH-SY5Y cells under both resting and treated conditions. We linked decreased susceptibility of the WT cells to higher and more stable Bcl-2 and decreased reactive oxygen species. Conversely, we linked G93A susceptibility to increased reactive oxygen species production since simultaneous administration of S-nitrosoglutathione and copper chelators protects from apoptosis. Furthermore, G93A cells showed a significant decrease of Bcl-2 expression and, as target of NO-derived radicals, showed lower cytochrome c oxidase activity. These results demonstrate that resistance to NO-mediated apoptosis is strictly related to the level and integrity of Cu,Zn-SOD and that the balance between reactive nitrogen and reactive oxygen species regulates neuroblastoma apoptosis. |
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Authors:
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M R Ciriolo; A De Martino; E Lafavia; L Rossi; M T Carrì; G Rotilio |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 275 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-21 Completed Date: 2000-03-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 5065-72 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, University of Chieti "G. D'Annunzio," via dei Vestini, 66100 Chieti, Italy. Ciriolo@bio.uniroma2.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyotrophic Lateral Sclerosis
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pathology Apoptosis / physiology* Caspases / metabolism Cytochrome c Group / metabolism Down-Regulation Enzyme Activation Glutathione / analogs & derivatives, metabolism Humans Neurons / enzymology, metabolism* Nitric Oxide / physiology* Nitroso Compounds / metabolism Oncogene Protein p21(ras) / metabolism Oxidative Stress Proto-Oncogene Proteins c-bcl-2 / metabolism S-Nitrosoglutathione Superoxide Dismutase / physiology* Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cytochrome c Group; 0/Nitroso Compounds; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 10102-43-9/Nitric Oxide; 57564-91-7/S-Nitrosoglutathione; 70-18-8/Glutathione; EC 1.15.1.1/Superoxide Dismutase; EC 3.4.22.-/Caspases; EC 3.6.5.2/Oncogene Protein p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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