Journal of Cell Science, Vol 107, Issue 6 1499-1507, Copyright © 1994 by Company of Biologists

JOURNAL ARTICLES

Apoptosis is induced in post-mitotic rat sympathetic neurons by arabinosides and topoisomerase II inhibitors in the presence of NGF

CE Tomkins, SN Edwards and AM Tolkovsky
Department of Human Anatomy, University of Oxford, UK.

Sympathetic neurons depend on nerve growth factor (NGF) for their survival and die by apoptosis when NGF is withdrawn, despite their post-mitotic state. Martin et al. (1990, J. Neurosci. 10, 184-193) showed that cytosine arabinoside, but no other arabinofuranosyl nucleoside, could induce cell death in the presence of NGF and they suggested that it may block a critical step in the NGF-signalling pathway. We show that cytosine arabinoside is not the only nucleoside capable of inducing apoptosis in sympathetic neurons in the presence of NGF. In newly isolated neurons from P0 rat pups cultured in the presence of NGF, all the arabinose nucleosides (adenine, cytosine, guanine and thymine) induce apoptosis at 10 microM when combined with 5-fluorodeoxyuridine treatment. Because 1-beta-arabinofuranosylcytosine is associated with double-strand breaks and chromosomal abberrations, we examined whether topoisomerase II inhibitors, which also cause double-strand breaks by stabilising the enzyme-DNA 'cleavable complex', were capable of promoting apoptosis in these neurons. Although P0 rat neurons are strictly postmitotic, topoisomerase II inhibitors teniposide and mitoxantrone induced them to die by apoptosis in the presence of NGF with the same apparent time-course as arabinose treatment or NGF withdrawal. By contrast, ICRF 193, a catalytic inhibitor of topoisomerase II, reduced the extent of apoptosis induced by mitoxantrone or teniposide by 80% if added simultaneously with the latter but by 2 hours it had no rescue effect, suggesting that topoisomerase II is highly active in these neurons. ICRF 193 also partially reduced the induction of fluorodeoxyuridine-dependent apoptosis by the arabinose nucleosides.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Colon-Cesario, J. Wang, X. Ramos, H. G. Garcia, J. J. Davila, J. Laguna, C. Rosado, and S. Pena de Ortiz An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning. J. Neurosci., May 17, 2006; 26(20): 5524 - 5533. [Abstract] [Full Text] [PDF]

				H. K. Wong, M. Fricker, A. Wyttenbach, A. Villunger, E. M. Michalak, A. Strasser, and A. M. Tolkovsky Mutually Exclusive Subsets of BH3-Only Proteins Are Activated by the p53 and c-Jun N-Terminal Kinase/c-Jun Signaling Pathways during Cortical Neuron Apoptosis Induced by Arsenite Mol. Cell. Biol., October 1, 2005; 25(19): 8732 - 8747. [Abstract] [Full Text] [PDF]

				M. Sedarous, E. Keramaris, M. O'Hare, E. Melloni, R. S. Slack, J. S. Elce, P. A. Greer, and D. S. Park Calpains Mediate p53 Activation and Neuronal Death Evoked by DNA Damage J. Biol. Chem., July 3, 2003; 278(28): 26031 - 26038. [Abstract] [Full Text] [PDF]

				C. G. Besirli and E. M. Johnson Jr. JNK-independent Activation of c-Jun during Neuronal Apoptosis Induced by Multiple DNA-damaging Agents J. Biol. Chem., June 13, 2003; 278(25): 22357 - 22366. [Abstract] [Full Text] [PDF]

				E. J. Morris, E. Keramaris, H. J. Rideout, R. S. Slack, N. J. Dyson, L. Stefanis, and D. S. Park Cyclin-Dependent Kinases and P53 Pathways Are Activated Independently and Mediate Bax Activation in Neurons after DNA Damage J. Neurosci., July 15, 2001; 21(14): 5017 - 5026. [Abstract] [Full Text] [PDF]

				L. Xue, J. H. Murray, and A. M. Tolkovsky The Ras/Phosphatidylinositol 3-Kinase and Ras/ERK Pathways Function as Independent Survival Modules Each of Which Inhibits a Distinct Apoptotic Signaling Pathway in Sympathetic Neurons J. Biol. Chem., March 17, 2000; 275(12): 8817 - 8824. [Abstract] [Full Text] [PDF]

				R.-W. Chen, P. A. Saunders, H. Wei, Z. Li, P. Seth, and D.-M. Chuang Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and p53 in Neuronal Apoptosis: Evidence That GAPDH Is Upregulated by p53 J. Neurosci., November 1, 1999; 19(21): 9654 - 9662. [Abstract] [Full Text] [PDF]

				C. N. G. Anderson and A. M. Tolkovsky A Role for MAPK/ERK in Sympathetic Neuron Survival: Protection against a p53-Dependent, JNK-Independent Induction of Apoptosis by Cytosine Arabinoside J. Neurosci., January 15, 1999; 19(2): 664 - 673. [Abstract] [Full Text] [PDF]

				D. S. Park, E. J. Morris, J. Padmanabhan, M. L. Shelanski, H. M. Geller, and L. A. Greene Cyclin-dependent Kinases Participate in Death of Neurons Evoked by DNA-damaging Agents J. Cell Biol., October 19, 1998; 143(2): 457 - 467. [Abstract] [Full Text] [PDF]

				D. S. Park, E. J. Morris, L. Stefanis, C. M. Troy, M. L. Shelanski, H. M. Geller, and L. A. Greene Multiple Pathways of Neuronal Death Induced by DNA-Damaging Agents, NGF Deprivation, and Oxidative Stress J. Neurosci., February 1, 1998; 18(3): 830 - 840. [Abstract] [Full Text] [PDF]

				D. S. Park, E. J. Morris, L. A. Greene, and H. M. Geller G1/S Cell Cycle Blockers and Inhibitors of Cyclin-Dependent Kinases Suppress Camptothecin-Induced Neuronal Apoptosis J. Neurosci., February 15, 1997; 17(4): 1256 - 1270. [Abstract] [Full Text] [PDF]

				A. R. Wakade, D. A. Przywara, K. C. Palmer, J. S. Kulkarni, and T. D. Wakade Deoxynucleoside Induces Neuronal Apoptosis Independent of Neurotrophic Factors J. Biol. Chem., July 28, 1995; 270(30): 17986 - 17992. [Abstract] [Full Text] [PDF]