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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2002
Author
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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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; . (2002) . 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. Journal of Neurochemistry, 2002, vol. 80, núm. 1, p. 126-139. https://doi.org/10.1046/j.0022-3042.2001.00695.x.
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Abstract
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.
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http://hdl.handle.net/10459.1/57017
DOI
https://doi.org/10.1046/j.0022-3042.2001.00695.x
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Journal of Neurochemistry, 2002, vol. 80, núm. 1, p. 126-139
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