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The prevention of the staurosporine-induced apoptosis by Bcl-X(L), but not by Bcl-2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells.
- Source :
-
Journal of neurochemistry [J Neurochem] 2002 Jan; Vol. 80 (1), pp. 126-39. - Publication Year :
- 2002
-
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.
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Caspase Inhibitors
Cell Differentiation drug effects
Humans
Neurites drug effects
Neurites pathology
Neurites physiology
Neuroblastoma physiopathology
Tumor Cells, Cultured
bcl-X Protein
Apoptosis drug effects
Enzyme Inhibitors pharmacology
Neuroblastoma pathology
Proto-Oncogene Proteins c-bcl-2 pharmacology
Staurosporine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 80
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11796751
- Full Text :
- https://doi.org/10.1046/j.0022-3042.2001.00695.x