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EnglishSH-SY5Y cells transfected with the enzymatically inactive Cu,Zn superoxide dismutase mutant H46R were more resistant to S-nitrosoglutathione (GSNO)-induced apoptosis. Cytochrome c release from mitochondria, caspase 3 activation, p53 up-regulation, p21 cleavage and Bcl-2 modulation, all involved in the apoptotic process, were significantly less altered with respect to untransfected cells. The H46R resistance to NO was associated with a higher content of reduced glutathione (GSH) and was abolished by blockage of glutathione synthesis. On the other hand, H46R cells were as sensitive as SH-SY5Y cells to puromycin-induced apoptosis; furthermore, they were more susceptible to apoptosis elicited by the superoxide-generating drug paraquat and to cell necrosis provoked by t-butyl hydroperoxide. These results confirm that the level of superoxide dismutase activity is fundamental for protecting cells against oxygen free radical challenge. Its impairment is not detrimental to cells exposed to NO, as long as the overall reducing power represented by GSH is assured. These results are relevant to explain a milder progression of the familial amyotrophic lateral sclerosis disease when associated with the H46R mutation.
Ciriolo, M.R., Aquilano, K., De Martino, A., Carri, M.T., & Rotilio, G. (2001). Differential role of superoxide and glutathione in S-nitrosoglutathione-mediated apoptosis: A rationale for mild forms of familial amyotrophic lateral sclerosis associated with less active Cu,Zn superoxide dismutase mutants. JOURNAL OF NEUROCHEMISTRY, 77(6), 1433-1443.
| Tipologia: | Articolo su rivista |
| Citazione: | Ciriolo, M.R., Aquilano, K., De Martino, A., Carri, M.T., & Rotilio, G. (2001). Differential role of superoxide and glutathione in S-nitrosoglutathione-mediated apoptosis: A rationale for mild forms of familial amyotrophic lateral sclerosis associated with less active Cu,Zn superoxide dismutase mutants. JOURNAL OF NEUROCHEMISTRY, 77(6), 1433-1443. |
| IF: | Con Impact Factor ISI |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore BIO/10 |
| Revisione (peer review): | Sì, ma tipo non specificato |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1046/j.1471-4159.2001.00383.x |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 2001 |
| Titolo: | Differential role of superoxide and glutathione in S-nitrosoglutathione-mediated apoptosis: A rationale for mild forms of familial amyotrophic lateral sclerosis associated with less active Cu,Zn superoxide dismutase mutants |
| Autori: | |
| Autori: | Ciriolo, MR; Aquilano, K; De Martino, A; Carri, MT; Rotilio, G. |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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http://hdl.handle.net/2108/53762
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