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Título:
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The prevention of the staurosporine-induced apoptosis by Bcl-XL, but not by Bcl-2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells
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Autor/a:
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Yuste Mateos, Víctor J. (Víctor José); Sánchez-López, Isabel; Solé Serra, Carme; Encinas Martín, Mario; Bayascas Ramírez, José Ramón; Boix Torras, Jacint; Comella i Carnicé, Joan Xavier
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Notas:
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Staurosporine is one of the best apoptotic inducers in different cell types including neuroblastomas. In this study we have compared the efficiency and final outcome of three different anti-apoptotic strategies in staurosporine-treated SH-SY5Y human neuroblastoma cells. At staurosporine concentrations up to 500 nm, z-VAD.fmk a broad-spectrum, noncompetitive inhibitor of caspases, reduced apoptosis in SH-SY5Y cells. At higher concentrations, z-VAD.fmk continued to inhibit caspases and the apoptotic phenotype but not cell death which seems to result from oxidative damage. Stable over-expression of Bcl-2 in SH-SY5Y protected cells from death at doses of staurosporine up to 1 microm. At higher doses, cytochrome c release from mitochondria occurred, caspases were activated and cells died by apoptosis. Therefore, we conclude that Bcl-2 increased the threshold for apoptotic cell death commitment. Over-expression of Bcl-X(L) was far more effective than Bcl-2. Bcl-X(L) transfected cells showed a remarkable resistance staurosporine-induced cytochrome c release and associated apoptotic changes and survived for up to 15 days in 1 microm staurosporine. In these conditions, SH-SY5Y displayed a remarkable phenotype of neuronal differentiation as assessed by neurite outgrowth and expression of neurofilament, Tau and MAP-2 neuronal specific proteins.
This work was founded by Spanish Govern Comisión Interministerial de Ciencia y Tecnología through the Plan Nacional de Salud y Farmacia (contract numbers SAF2000-0164-C02-01 and 1FD97-0514-02-01) and Ajuntament de Lleida. VJY is a predoctoral fellow supported by the European Union contracts BIO4-CT96-0433 and QLG3-CT-1999-00602. JRB was supported by grant 1FD97-0514- C02-01 from Spanish Ministry of Science and Technology. |
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Materia(s):
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-Bcl-2
-Bcl-XL
-Neuritogenesis
-SH-SY5Y cells |
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Derechos:
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(c) International Society for Neurochemistry, 2002
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Wiley
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Compartir:
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