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
Yuste Mateos, Víctor J. (Víctor José)
Solé Serra, Carme
Bayascas Ramírez, José Ramón
Comella i Carnicé, Joan Xavier
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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.
Is part ofJournal of Neurochemistry, 2002, vol. 80, núm. 1, p. 126-139
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Yuste Mateos, Víctor J. (Víctor José); Bayascas Ramírez, José Ramón; Llecha Cano, Núria; Sánchez-López, Isabel; Boix Torras, Jacint; Comella i Carnicé, Joan Xavier (American Society for Biochemistry and Molecular Biology, 2001)Caspase-activated DNase is responsible for the oligonucleosomal DNA degradation during apoptosis. DNA degradation is thought to be important for multicellular organisms to prevent oncogenic transformation or as a mechanism ...
Serum Deprivation and Protein Synthesis Inhibition Induce Two Different Apoptotic Processes in N18 Neuroblastoma Cells Fibla Palazón, Joan; Yuste Mateos, Víctor J. (Víctor José); Piulats, J.M; Llecha Cano, Núria; Comella i Carnicé, Joan Xavier; Boix Torras, Jacint (Elsevier, 1998)N18 are murine neuroblastoma cells that underwent cell death upon serum deprivation or inhibition of protein synthesis by means of cycloheximide (CHX). In both cases, an ultrastructural morphology and an internucleosomal ...
Characterization of the Cell Death Process Induced by Staurosporine in Human Neuroblastoma Cell Lines Boix Torras, Jacint; Llecha Cano, Núria; Yuste Mateos, Víctor J. (Víctor José); Comella i Carnicé, Joan Xavier (Elsevier, 1997)Staurosporine is a potent and non-specific inhibitor of protein kinases. There is also evidence of staurosporine being a potent inducer of apoptosis. In several human neuroblastoma cell lines (SH-SY5Y, NB69, IMR-5 and ...