QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (170) Citing Articles via Google Scholar Google Scholar Articles by Estus, S. Articles by Rydel, R. E. Search for Related Content PubMed PubMed Citation Articles by Estus, S. Articles by Rydel, R. E.

 Previous Article  |  Next Article 

Volume 17, Number 20, Issue of October 15, 1997 pp. 7736-7745
Copyright ©1997 Society for Neuroscience

Aggregated Amyloid- Protein Induces Cortical Neuronal Apoptosis and Concomitant "Apoptotic" Pattern of Gene Induction

Received June 19, 1997; accepted July 29, 1997.

Steven Estus¹, H. Michael Tucker¹, Corlia van Rooyen¹, Sarah Wright², Elizabeth F. Brigham², Mark Wogulis², and Russell E. Rydel²

¹ Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, and ² Athena Neurosciences, South San Francisco, California 94080

To gain a molecular understanding of neuronal responses to amyloid- peptide (A), we have analyzed the effects of A treatment on neuronal gene expression in vitro by quantitative reverse transcription-PCR and in situ hybridization. Treatment of cultured rat cortical neurons with A_1-40 results in a widespread apoptotic neuronal death. Associated with death is an induction of several members of the immediate early gene family. Specifically, we (1) report the time-dependent and robust induction of c-jun, junB, c-fos, and fosB, as well as transin, which is induced by c-Jun/c-Fos heterodimers and encodes an extracellular matrix protease; these gene inductions appear to be selective because other Jun and Fos family members, i.e., junD and fra-1, are induced only marginally; (2) show that the c-jun induction is widespread, whereas c-fos expression is restricted to a subset of neurons, typically those with condensed chromatin, which is a hallmark of apoptosis; (3) correlate gene induction and neuronal death by showing that each has a similar dose-response to A; and (4) demonstrate that both cell death and immediate early gene induction are dependent on A aggregation state. This overall gene expression pattern during this "physiologically inappropriate" apoptotic stimulus is markedly similar to the pattern we previously identified after a "physiologically appropriate" stimulus, i.e., the NGF deprivation-induced death of sympathetic neurons. Hence, the parallels identified here further our understanding of the genetic alterations that may lead neurons to apoptosis in response to markedly different insults.

Key words: amyloid; apoptosis; immediate early genes; Alzheimer's disease; programmed cell death

This article has been cited by other articles:

				E. Sturchler, A. Galichet, M. Weibel, E. Leclerc, and C. W. Heizmann Site-Specific Blockade of RAGE-Vd Prevents Amyloid-{beta} Oligomer Neurotoxicity J. Neurosci., May 14, 2008; 28(20): 5149 - 5158. [Abstract] [Full Text] [PDF]

				C. Galvan, P. G. Camoletto, F. Cristofani, P. P. Van Veldhoven, and M. D. Ledesma Anomalous Surface Distribution of Glycosyl Phosphatidyl Inositol-anchored Proteins in Neurons Lacking Acid Sphingomyelinase Mol. Biol. Cell, February 1, 2008; 19(2): 509 - 522. [Abstract] [Full Text] [PDF]

				H. Zhu, H. M. Tucker, K. E. Grear, J. F. Simpson, A. K. Manning, L. A. Cupples, and S. Estus A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol Hum. Mol. Genet., July 15, 2007; 16(14): 1765 - 1772. [Abstract] [Full Text] [PDF]

				T. M. Malm, H. Iivonen, G. Goldsteins, V. Keksa-Goldsteine, T. Ahtoniemi, K. Kanninen, A. Salminen, S. Auriola, T. Van Groen, H. Tanila, et al. Pyrrolidine Dithiocarbamate Activates Akt and Improves Spatial Learning in APP/PS1 Mice without Affecting {beta}-Amyloid Burden J. Neurosci., April 4, 2007; 27(14): 3712 - 3721. [Abstract] [Full Text] [PDF]

				S. C. Biswas, Y. Shi, J.-P. G. Vonsattel, C. L. Leung, C. M. Troy, and L. A. Greene Bim Is Elevated in Alzheimer's Disease Neurons and Is Required for {beta}-Amyloid-Induced Neuronal Apoptosis J. Neurosci., January 24, 2007; 27(4): 893 - 900. [Abstract] [Full Text] [PDF]

				M. A. Abad, M. Enguita, N. DeGregorio-Rocasolano, I. Ferrer, and R. Trullas Neuronal Pentraxin 1 Contributes to the Neuronal Damage Evoked by Amyloid-{beta} and Is Overexpressed in Dystrophic Neurites in Alzheimer's Brain J. Neurosci., December 6, 2006; 26(49): 12735 - 12747. [Abstract] [Full Text] [PDF]

				S. Qin, C. Colin, I. Hinners, A. Gervais, C. Cheret, and M. Mallat System Xc- and apolipoprotein E expressed by microglia have opposite effects on the neurotoxicity of amyloid-beta peptide 1-40. J. Neurosci., March 22, 2006; 26(12): 3345 - 3356. [Abstract] [Full Text] [PDF]

				S.-Y. Park and A. Ferreira The Generation of a 17 kDa Neurotoxic Fragment: An Alternative Mechanism by which Tau Mediates {beta}-Amyloid-Induced Neurodegeneration J. Neurosci., June 1, 2005; 25(22): 5365 - 5375. [Abstract] [Full Text] [PDF]

				N. L. Malinin, S. Wright, P. Seubert, D. Schenk, and I. Griswold-Prenner Amyloid-{beta} neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity PNAS, February 22, 2005; 102(8): 3058 - 3063. [Abstract] [Full Text] [PDF]

				M. Wogulis, S. Wright, D. Cunningham, T. Chilcote, K. Powell, and R. E. Rydel Nucleation-Dependent Polymerization Is an Essential Component of Amyloid-Mediated Neuronal Cell Death J. Neurosci., February 2, 2005; 25(5): 1071 - 1080. [Abstract] [Full Text] [PDF]

				M. Yao, T.-V. V. Nguyen, and C. J. Pike {beta}-Amyloid-Induced Neuronal Apoptosis Involves c-Jun N-Terminal Kinase-Dependent Downregulation of Bcl-w J. Neurosci., February 2, 2005; 25(5): 1149 - 1158. [Abstract] [Full Text] [PDF]

				Y. N. Dong, E. A. Waxman, and D. R. Lynch Interactions of Postsynaptic Density-95 and the NMDA Receptor 2 Subunit Control Calpain-Mediated Cleavage of the NMDA Receptor J. Neurosci., December 8, 2004; 24(49): 11035 - 11045. [Abstract] [Full Text] [PDF]

				Q. Wang, D. M. Walsh, M. J. Rowan, D. J. Selkoe, and R. Anwyl Block of Long-Term Potentiation by Naturally Secreted and Synthetic Amyloid {beta}-Peptide in Hippocampal Slices Is Mediated via Activation of the Kinases c-Jun N-Terminal Kinase, Cyclin-Dependent Kinase 5, and p38 Mitogen-Activated Protein Kinase as well as Metabotropic Glutamate Receptor Type 5 J. Neurosci., March 31, 2004; 24(13): 3370 - 3378. [Abstract] [Full Text] [PDF]

				K. Del Villar and C. A. Miller Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons PNAS, March 23, 2004; 101(12): 4210 - 4215. [Abstract] [Full Text] [PDF]

				R. Li, L. Yang, K. Lindholm, Y. Konishi, X. Yue, H. Hampel, D. Zhang, and Y. Shen Tumor Necrosis Factor Death Receptor Signaling Cascade Is Required for Amyloid-{beta} Protein-Induced Neuron Death J. Neurosci., February 18, 2004; 24(7): 1760 - 1771. [Abstract] [Full Text] [PDF]

				S. W. Rau, D. B. Dubal, M. Bottner, and P. M. Wise Estradiol Differentially Regulates c-Fos after Focal Cerebral Ischemia J. Neurosci., November 19, 2003; 23(33): 10487 - 10494. [Abstract] [Full Text] [PDF]

				A. M. Minogue, A. W. Schmid, M. P. Fogarty, A. C. Moore, V. A. Campbell, C. E. Herron, and M. A. Lynch Activation of the c-Jun N-terminal Kinase Signaling Cascade Mediates the Effect of Amyloid-{beta} on Long Term Potentiation and Cell Death in Hippocampus: A ROLE FOR INTERLEUKIN-1{beta}? J. Biol. Chem., July 18, 2003; 278(30): 27971 - 27980. [Abstract] [Full Text] [PDF]

				I. Qahwash, K. L. Weiland, Y. Lu, R. W. Sarver, R. F. Kletzien, and R. Yan Identification of a Mutant Amyloid Peptide That Predominantly Forms Neurotoxic Protofibrillar Aggregates J. Biol. Chem., June 13, 2003; 278(25): 23187 - 23195. [Abstract] [Full Text] [PDF]

				I. Sponne, A. Fifre, B. Drouet, C. Klein, V. Koziel, M. Pincon-Raymond, J.-L. Olivier, J. Chambaz, and T. Pillot Apoptotic Neuronal Cell Death Induced by the Non-fibrillar Amyloid-beta Peptide Proceeds through an Early Reactive Oxygen Species-dependent Cytoskeleton Perturbation J. Biol. Chem., January 24, 2003; 278(5): 3437 - 3445. [Abstract] [Full Text] [PDF]

				Y. Uchida Overexpression of Full-length but Not N-terminal Truncated Isoform of Microtubule-associated Protein (MAP) 1B Accelerates Apoptosis of Cultured Cortical Neurons J. Biol. Chem., January 3, 2003; 278(1): 366 - 371. [Abstract] [Full Text] [PDF]

				T. Fath, J. Eidenmuller, and R. Brandt Tau-Mediated Cytotoxicity in a Pseudohyperphosphorylation Model of Alzheimer's Disease J. Neurosci., November 15, 2002; 22(22): 9733 - 9741. [Abstract] [Full Text] [PDF]

				R. Onuki, A. Nagasaki, H. Kawasaki, T. Baba, T. Q. P. Uyeda, and K. Taira Confirmation by FRET in individual living cells of the absence of significant amyloid beta -mediated caspase 8 activation PNAS, November 12, 2002; 99(23): 14716 - 14721. [Abstract] [Full Text] [PDF]

				M. P. Mattson, S. L. Chan, and W. Duan Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior Physiol Rev, July 1, 2002; 82(3): 637 - 672. [Abstract] [Full Text] [PDF]

				Z.-S. Ji, R. D. Miranda, Y. M. Newhouse, K. H. Weisgraber, Y. Huang, and R. W. Mahley Apolipoprotein E4 Potentiates Amyloid beta Peptide-induced Lysosomal Leakage and Apoptosis in Neuronal Cells J. Biol. Chem., June 7, 2002; 277(24): 21821 - 21828. [Abstract] [Full Text] [PDF]

				M. L. Spencer, H. Shao, and D. A. Andres Induction of Neurite Extension and Survival in Pheochromocytoma Cells by the Rit GTPase J. Biol. Chem., May 31, 2002; 277(23): 20160 - 20168. [Abstract] [Full Text] [PDF]

				M. L. Spencer, H. Shao, H. M. Tucker, and D. A. Andres Nerve Growth Factor-dependent Activation of the Small GTPase Rin J. Biol. Chem., May 10, 2002; 277(20): 17605 - 17615. [Abstract] [Full Text] [PDF]

				H. Okazawa and S. Estus The JNK/c-Jun cascade and Alzheimer's disease American Journal of Alzheimer's Disease and Other Dementias, March 1, 2002; 17(2): 79 - 88. [Abstract] [PDF]

				R. Williamson, T. Scales, B. R. Clark, G. Gibb, C. H. Reynolds, S. Kellie, I. N. Bird, I. M. Varndell, P. W. Sheppard, I. Everall, et al. Rapid Tyrosine Phosphorylation of Neuronal Proteins Including Tau and Focal Adhesion Kinase in Response to Amyloid-beta Peptide Exposure: Involvement of Src Family Protein Kinases J. Neurosci., January 1, 2002; 22(1): 10 - 20. [Abstract] [Full Text] [PDF]

				G. Ermak, T. E. Morgan, and K. J. A. Davies Chronic Overexpression of the Calcineurin Inhibitory Gene DSCR1 (Adapt78) Is Associated with Alzheimer's Disease J. Biol. Chem., October 12, 2001; 276(42): 38787 - 38794. [Abstract] [Full Text] [PDF]

				Y. Morishima, Y. Gotoh, J. Zieg, T. Barrett, H. Takano, R. Flavell, R. J. Davis, Y. Shirasaki, and M. E. Greenberg {beta}-Amyloid Induces Neuronal Apoptosis Via a Mechanism that Involves the c-Jun N-Terminal Kinase Pathway and the Induction of Fas Ligand J. Neurosci., October 1, 2001; 21(19): 7551 - 7560. [Abstract] [Full Text] [PDF]

				G. S. De Zutter and R. J. Davis Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway PNAS, May 3, 2001; (2001) 111027698. [Abstract] [Full Text]

				A. Mukherjee, E.-s. Song, M. Kihiko-Ehmann, J. P. Goodman Jr, J. St. Pyrek, S. Estus, and L. B. Hersh Insulysin Hydrolyzes Amyloid beta Peptides to Products That Are Neither Neurotoxic Nor Deposit on Amyloid Plaques J. Neurosci., December 1, 2000; 20(23): 8745 - 8749. [Abstract] [Full Text] [PDF]

				H. M. Tucker, M. Kihiko, J. N. Caldwell, S. Wright, T. Kawarabayashi, D. Price, D. Walker, S. Scheff, J. P. McGillis, R. E. Rydel, et al. The Plasmin System Is Induced by and Degrades Amyloid-beta Aggregates J. Neurosci., June 1, 2000; 20(11): 3937 - 3946. [Abstract] [Full Text] [PDF]

				C. M. Troy, S. A. Rabacchi, W. J. Friedman, T. F. Frappier, K. Brown, and M. L. Shelanski Caspase-2 Mediates Neuronal Cell Death Induced by beta -Amyloid J. Neurosci., February 15, 2000; 20(4): 1386 - 1392. [Abstract] [Full Text] [PDF]

				D. G. Nicholls and S. L. Budd Mitochondria and Neuronal Survival Physiol Rev, January 1, 2000; 80(1): 315 - 360. [Abstract] [Full Text] [PDF]

				A. COPANI, F. CONDORELLI, A. CARUSO, C. VANCHERI, A. SALA, A. M. GIUFFRIDA STELLA, P. L. CANONICO, F. NICOLETTI, and M. A. SORTINO Mitotic signaling by {beta}-amyloid causes neuronal death FASEB J, December 1, 1999; 13(15): 2225 - 2234. [Abstract] [Full Text]

				D. M. Hartley, D. M. Walsh, C. P. Ye, T. Diehl, S. Vasquez, P. M. Vassilev, D. B. Teplow, and Dennis. J. Selkoe Protofibrillar Intermediates of Amyloid beta -Protein Induce Acute Electrophysiological Changes and Progressive Neurotoxicity in Cortical Neurons J. Neurosci., October 15, 1999; 19(20): 8876 - 8884. [Abstract] [Full Text] [PDF]

				D. B. Dubal, P. J. Shughrue, M. E. Wilson, I. Merchenthaler, and P. M. Wise Estradiol Modulates bcl-2 in Cerebral Ischemia: A Potential Role for Estrogen Receptors J. Neurosci., August 1, 1999; 19(15): 6385 - 6393. [Abstract] [Full Text] [PDF]

				K. Imaizumi, T. Morihara, Y. Mori, T. Katayama, M. Tsuda, T. Furuyama, A. Wanaka, M. Takeda, and M. Tohyama The Cell Death-promoting Gene DP5, Which Interacts with the BCL2 Family, Is Induced during Neuronal Apoptosis Following Exposure to Amyloid beta  Protein J. Biol. Chem., March 19, 1999; 274(12): 7975 - 7981. [Abstract] [Full Text] [PDF]

				C.-N. Wang, C.-W. Chi, Y.-L. Lin, C.-F. Chen, and Y.-J. Shiao The Neuroprotective Effects of Phytoestrogens on Amyloid beta Protein-induced Toxicity Are Mediated by Abrogating the Activation of Caspase Cascade in Rat Cortical Neurons J. Biol. Chem., February 9, 2001; 276(7): 5287 - 5295. [Abstract] [Full Text] [PDF]

				G. S. De Zutter and R. J. Davis Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway PNAS, May 22, 2001; 98(11): 6168 - 6173. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help