Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Taxol-induced peripheral neuropathy is a commonly-occurring side-effect in the treatment of cancer patients with taxoteres or taxanes. Taxol is known to induce apoptosis in a number of tumor cells. This report documents that, similar to proliferating cells, taxol induces apoptosis in NGF-differentiated PC12 cells, as assessed by exogenous FITC-annexin-V binding and nuclear fragmentation. It is shown that PC12 cells that stably overexpress Bcl-2 are protected against the toxic effect of taxol, as evidenced by the XTT assay and by a decreased fraction of propididum iodide positive cells in a dye exclusion test. Also the number of annexin-V-positive cells and the number of fragmented nuclei are lower in the Bcl-2 transfected cells. The effect is similar to the protective effect of Bcl-2 against NGF deprivation in differentiated PC12 cells. Although taxol forced both wild-type and Bcl-2-overexpressing cells into a mitotic state, only in Bcl-2-overexpressing cells did this lead to the appearance of metabolically active, multi-nucleated cells. This suggests that Bcl-2 is able to induce an alternative escape pathway, downstream of the G2/M block, in taxol-treated differentiated PC12 cells.
- Shu C, YangW, Kuo M-L, Huang T-S. Cell cycle G2/M arrest and activation of cyclin-dependent kinases associated with lowdose paclitaxel-induced sub-G1 apoptosis. Apoptosis 1997; 2: 463–470.
- Nuydens R, de Jong M, Van Den Kieboom G, et al. Okadaic acid-induced apoptosis in neuronal cells: Evidence for a abortive mitotic attempt. J Neurochem 1998; 70: 1124–1133.
- Freeman R, Estus S, Johnson E Jr. Analysis of cell cycle related gene expression in post-mitotic neurons: Selective induction of cyclin D1 during programmed cell death. Neuron 1994; 12: 343–355. Bcl-2 protects neuronal cells from taxol toxicity
- Bonfoco E, Ceccatelli S, Manzo L, Nicotera P. Colchicine induces apoptosis in cerebellar granule cells. Exp Cell Res 1996; 218: 189–200.
- Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nature Medicine 1997; 3: 614–620.
- Tanabe H, Eguchi Y, Kamada S, Martinou JC, Tsujimoto Y. Susceptibility of cerebellar neurons derived from Bcl-2-deficient and transgenic mice to cell death. Eur J Neurosci 1997; 9: 848–856.
- Ottilie S, Diaz JL, Chang J, et al. Structural and functional complementation of an inactive Bcl-2 mutant by Bax truncation. J Biol Chem 1997; 272(27): 16955–16961.
- Schutte B, Nuydens R, Geerts H, Ramaekers F. Annexin V binding assay as a tool to measure apoptosis in differentiated neuronal cells. J Neurosci Methods 1998; 86: 63–69.
- Park DS, Morris EJ, Stefanis L, et al. Multiple pathways of neuronal death induced by DNA-damaging agents, NGF deprivation and oxidative stress. J Neurosci 1998; 18(3): 830–840.
- Bergeron L, Yuan J. Sealing one's fate: Control of cell death in neurons. Curr Opin Neurobiol 1998; 8: 55–63.
- Lam M, Dubyak G, Chen L, Nunez G, Miesfeld R, Distelhorst C. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci 1994; 91: 6569–6573.
- Zamzami N, Susin S, Marchetti P, et al. Mitochondrial control of nuclear apoptosis. J Exp Med 1996; 138: 1533–1544.
- Suzuki A, Tsutomi Y. Bcl-2 accelerates the neuronal differentiation: New evidence approaching to the biofunction of Bcl-2 in the neuronal system. Brain Research 1998; 801: 59–66.
- Malgrange B, Delree P, Rigo JM, Baron H, Moonen G. Image analysis of neuritic regeneration by adult dorsal root ganglion neurons in culture: Quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3. J Neurosci Methods 1994; 53: 111–122.
- Furukawa K, Mattson MP. Taxol stabilizes Ca2+ and protects hippocampal neurons against excitotoxicity. Brain Res 1995; 689: 141–146.
- Burke WJ, Raghu G, Strong R. Taxol protects against calciummediated cell death of differentiated rat pheochromocytoma cells. Life Sciences 1994; 55: 313–319.
- Martinou J, Dubois-Dauphin M, Staple J, et al. Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 1994; 13: 1017–1030.
- Sagot Y, Dubois-Dauphin M, Tan S, et al. Bcl-2 overexpression prevents motorneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease. J Neurosci 1995; 15: 7727–7733.
- Haldar S, Basu A, Croce M. Bcl-2 is the guardian of microtubule integrity. Cancer Res 1997; 57: 229–233.
- Minn A, Boise L, Thompson C. Expression of Bcl-XL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage. Genes & Development 1996: 10: 2621–2631.
- Ibrado A, Huang Y, Fang G, Bhalla K. Bcl-XL overexpression inhibits taxol-induced Yama protease activity and apoptosis. Cell Growth & Differentiation 1996; 7: 1087–1094.
- Bcl-2 protects neuronal cells against taxol-induced apoptosis by inducing multi-nucleation
Volume 5, Issue 4 , pp 335-343
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Department of Neurobiology, Janssen Research Foundation, Beerse, Belgium;
- 2. Department of Molecular Cell Biology and Genetics, Maastricht University, Maastricht, The Netherlands
- 3. Department of Biochemistry, University of Antwerp, Antwerp, Belgium
- 4. Oncology Group, Janssen Research Foundation, Spring House, Pennsylvania, USA