Internucleosomal DNA cleavage and neuronal cell survival/death

doi:10.1083/jcb.122.3.523

This Article

	Full Text (PDF, 2136K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Batistatou, A.
	Articles by Greene, L. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Batistatou, A.
	Articles by Greene, L. A.


Social Bookmarking

	What's this?

ARTICLES

Internucleosomal DNA cleavage and neuronal cell survival/death

A Batistatou and LA Greene
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York 10032.

Serum-free PC12 cell cultures have been used to study the mechanisms of neuronal death after neurotrophic factor deprivation. We previously reported that PC12 cells undergo "apoptotic" internucleosomal DNA cleavage after withdrawal of trophic support. Here, we have used a sensitive method to detect PC12 cell DNA fragmentation within three hrs of serum removal and have exploited this assay to examine several aspects regarding the mechanisms of neuronal survival/death. Major advantages of this assay are that it permits acute experiments to be performed well before other manifest signs of cell death and under conditions that cannot be applied chronically. We find that this apopotic DNA fragmentation is distinct from the random DNA degradation that occurs during necrotic death. Major observations include the following: (a) There is a good correlation between the ability of trophic substances to promote PC12 cell survival and to inhibit early DNA fragmentation. (b) Phorbol ester, an activator of PKC, acutely suppresses DNA fragmentation, but does not promote long-term survival or inhibition of endonuclease activity when applied chronically due to its downregulation of PKC. (c) Cells undergoing apoptosis within 3 h of serum withdrawal have a "commitment point" of only 1.0-1.5 h beyond which they can no longer be rescued by NGF. (d) Aurin, a non-carboxylic analog of the endonuclease inhibitor ATA, also inhibits DNA fragmentation and promotes short-term survival of PC12 cells. (e) Macromolecular synthesis is not required for DNA fragmentation or for NGF to prevent this event. (f) Extracellular Ca2+ is not required for internucleosomal DNA cleavage caused by serum withdrawal or for suppression of this by NGF. (g) DNA fragmentation can also be detected in cultures of rat sympathetic neurons as early as 10 h after removal of NGF. As in PC12 cell cultures, this precedes morphological signs of cell death.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Fishman-Jacob, T., Reznichenko, L., Youdim, M. B. H., Mandel, S. A. (2009). A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A. J. Biol. Chem. 284: 32835-32845 [Abstract] [Full Text]
Tozaki-Saitoh, H., Koizumi, S., Sato, Y., Tsuda, M., Nagao, T., Inoue, K. (2006). Retinoic Acids Increase P2X2 Receptor Expression through the 5'-Flanking Region of P2rx2 Gene in Rat Phaeochromocytoma PC-12 Cells. Mol. Pharmacol. 70: 319-328 [Abstract] [Full Text]
Arthur, D. B., Georgi, S., Akassoglou, K., Insel, P. A. (2006). Inhibition of apoptosis by P2Y2 receptor activation: novel pathways for neuronal survival.. J. Neurosci. 26: 3798-3804 [Abstract] [Full Text]
Parran, D. K., Barker, A., Ehrich, M. (2005). Effects of Thimerosal on NGF Signal Transduction and Cell Death in Neuroblastoma Cells. Toxicol Sci 86: 132-140 [Abstract] [Full Text]
Vaghefi, H., Hughes, A. L., Neet, K. E. (2004). Nerve Growth Factor Withdrawal-mediated Apoptosis in Naive and Differentiated PC12 Cells through p53/Caspase-3-dependent and -independent Pathways. J. Biol. Chem. 279: 15604-15614 [Abstract] [Full Text]
Wang, X., Chen, L., Maures, T. J., Herrington, J., Carter-Su, C. (2004). SH2-B Is a Positive Regulator of Nerve Growth Factor-mediated Activation of the Akt/Forkhead Pathway in PC12 Cells. J. Biol. Chem. 279: 133-141 [Abstract] [Full Text]
Hinck, L., Van Der Smissen, P., Heusterpreute, M., Donnay, I., De Hertogh, R., Pampfer, S. (2001). Identification of Caspase-3 and Caspase-Activated Deoxyribonuclease in Rat Blastocysts and Their Implication in the Induction of Chromatin Degradation (but Not Nuclear Fragmentation) by High Glucose. Biol. Reprod. 64: 555-562 [Abstract] [Full Text]
Gabriella De Vita, , Melillo, R. M., Carlomagno, F., Visconti, R., Castellone, M. D., Bellacosa, A., Billaud, M., Fusco, A., Tsichlis, P. N., Santoro, M. (2000). Tyrosine 1062 of RET-MEN2A Mediates Activation of Akt (Protein Kinase B) and Mitogen-activated Protein Kinase Pathways Leading to PC12 Cell Survival. Cancer Res. 60: 3727-3731 [Abstract] [Full Text]
Eldadah, B. A., Ren, R. F., Faden, A. I. (2000). Ribozyme-Mediated Inhibition of Caspase-3 Protects Cerebellar Granule Cells from Apoptosis Induced by Serum-Potassium Deprivation. J. Neurosci. 20: 179-186 [Abstract] [Full Text]
Stein, J. C., Hansen, G. (1999). Mannose Induces an Endonuclease Responsible for DNA Laddering in Plant Cells. Plant Physiol. 121: 71-80 [Abstract] [Full Text]
Grønborg, M., Johansen, T. E., Peters, D., Ahring, P. K., Drejer, J., Møller, A., Jensen, L. H. (1999). Neuroprotection by a Novel Compound, NS521. J. Pharmacol. Exp. Ther. 290: 348-353 [Abstract] [Full Text]
Shen, L., Dean, N. M., Glazer, R. I. (1999). Induction of p53-Dependent, Insulin-Like Growth Factor-Binding Protein-3-Mediated Apoptosis in Glioblastoma Multiforme Cells by a Protein Kinase Calpha Antisense Oligonucleotide. Mol. Pharmacol. 55: 396-402 [Abstract] [Full Text]
O'Rourke, D. M., Kao, G. D., Singh, N., Park, B.-W., Muschel, R. J., Wu, C.-j., Greene, M. I. (1998). Conversion of a radioresistant phenotype to a more sensitive one by disabling erbB receptor signaling in human cancer cells. Proc. Natl. Acad. Sci. USA 95: 10842-10847 [Abstract] [Full Text]
Zechner, D., Craig, R., Hanford, D. S., McDonough, P. M., Sabbadini, R. A., Glembotski, C. C. (1998). MKK6 Activates Myocardial Cell NF-kappa B and Inhibits Apoptosis in a p38 Mitogen-activated Protein Kinase-dependent Manner. J. Biol. Chem. 273: 8232-8239 [Abstract] [Full Text]
Park, D. S., Levine, B., Ferrari, G., Greene, L. A. (1997). Cyclin Dependent Kinase Inhibitors and Dominant Negative Cyclin Dependent Kinase 4�and 6�Promote Survival of NGF-Deprived Sympathetic Neurons. J. Neurosci. 17: 8975-8983 [Abstract] [Full Text]
Holgado-Madruga, M., Moscatello, D. K., Emlet, D. R., Dieterich, R., Wong, A. J. (1997). Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth�factor. Proc. Natl. Acad. Sci. USA 94: 12419-12424 [Abstract] [Full Text]
Grimes, M. L., Beattie, E., Mobley, W. C. (1997). A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA. Proc. Natl. Acad. Sci. USA 94: 9909-9914 [Abstract] [Full Text]
Eldadah, B. A., Yakovlev, A. G., Faden, A. I. (1997). The Role of CED-3-Related Cysteine Proteases in Apoptosis of Cerebellar Granule Cells. J. Neurosci. 17: 6105-6113 [Abstract] [Full Text]
Park, D. S., Morris, E. J., Greene, L. A., Geller, H. M. (1997). G1/S Cell Cycle Blockers and Inhibitors of Cyclin-Dependent Kinases Suppress Camptothecin-Induced Neuronal Apoptosis. J. Neurosci. 17: 1256-1270 [Abstract] [Full Text]
Stefanis, L., Park, D. S., Yan, C. Y. I., Farinelli, S. E., Troy, C. M., Shelanski, M. L., Greene, L. A. (1996). Induction of CPP32-like Activity in PC12 Cells by Withdrawal of Trophic Support. DISSOCIATION FROM APOPTOSIS. J. Biol. Chem. 271: 30663-30671 [Abstract] [Full Text]
Park, D. S., Stefanis, L., Yan, C. Y. I., Farinelli, S. E., Greene, L. A. (1996). Ordering the Cell Death Pathway. DIFFERENTIAL EFFECTS OF BCL2, AN INTERLEUKIN-1-CONVERTING ENZYME FAMILY PROTEASE INHIBITOR, AND OTHER SURVIVAL AGENTS ON JNK ACTIVATION IN SERUM/NERVE GROWTH FACTOR-DEPRIVED PC12 CELLS. J. Biol. Chem. 271: 21898-21905 [Abstract] [Full Text]
Park, D. S., Farinelli, S. E., Greene, L. A. (1996). Inhibitors of Cyclin-dependent Kinases Promote Survival of Post-mitotic Neuronally Differentiated PC12 Cells and Sympathetic Neurons. J. Biol. Chem. 271: 8161-8169 [Abstract] [Full Text]
Xia, Z., Dickens, M., Raingeaud, J.�l, Davis, R. J., Greenberg, M. E. (1995). Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis. Science 270: 1326-1331 [Abstract]
Yan, C. Y. I., Ferrari, G., Greene, L. A. (1995). N-Acetylcysteine-promoted Survival of PC12 Cells Is Glutathione-independent but Transcription-dependent. J. Biol. Chem. 270: 26827-26832 [Abstract] [Full Text]
Okada, N., Koizumi, S. (1995). A Neuroprotective Compound, Aurin Tricarboxylic Acid, Stimulates the Tyrosine Phosphorylation Cascade in PC12 Cells. J. Biol. Chem. 270: 16464-16469 [Abstract] [Full Text]
Yao, R, Cooper, G. (1995). Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267: 2003-2006 [Abstract]
Ferrari, G., Anderson, B. L., Stephens, R. M., Kaplan, D. R., Greene, L. A. (1995). Prevention of Apoptotic Neuronal Death by G[IMAGE] Ganglioside. J. Biol. Chem. 270: 3074-3080 [Abstract] [Full Text]
Anastasiadis, P. Z., Jiang, H., Bezin, L., Kuhn, D. M., Levine, R. A. (2001). Tetrahydrobiopterin Enhances Apoptotic PC12 Cell Death following Withdrawal of Trophic Support. J. Biol. Chem. 276: 9050-9058 [Abstract] [Full Text]