HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by PEDERSEN, W. A. Articles by MATTSON, M. P. Search for Related Content PubMed PubMed Citation Articles by PEDERSEN, W. A. Articles by MATTSON, M. P.

The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis

WARD A. PEDERSEN^*, HONG LUO^*, INNA KRUMAN^*, EDWARD KASARSKIS and MARK P. MATTSON^*,§1

^* Sanders-Brown Research Center on Aging,
Department of Neurology, and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA; and
^§ Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA

¹Correspondence: Laboratory of Neurosciences, National Institute on Aging, GRC 4F01, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA. E-mail: mattsonm{at}grc.nia.nih.gov

Prostate apoptosis response-4 (Par-4), a protein containing a leucine zipper domain within a death domain, is up-regulated in prostate cancer cells and hippocampal neurons induced to undergo apoptosis. Here, we report higher Par-4 levels in lumbar spinal cord samples from patients with amyotrophic lateral sclerosis (ALS) than in lumbar spinal cord samples from neurologically normal patients. We also compared the levels of Par-4 in lumbar spinal cord samples from wild-type and transgenic mice expressing the human Cu/Zn-superoxide dismutase gene with a familial ALS mutation. Relative to control samples, higher Par-4 levels were observed in lumbar spinal cord samples prepared from the transgenic mice at a time when they had hind-limb paralysis. Immunohistochemical analyses of human and mouse lumbar spinal cord sections revealed that Par-4 is localized to motor neurons in the ventral horn region. In culture studies, exposure of primary mouse spinal cord motor neurons or NSC-19 motor neuron cells to oxidative insults resulted in a rapid and large increase in Par-4 levels that preceded apoptosis. Pretreatment of the motor neuron cells with a Par-4 antisense oligonucleotide prevented oxidative stress-induced apoptosis and reversed oxidative stress-induced mitochondrial dysfunction that preceded apoptosis. Collectively, these data suggest a role for Par-4 in models of motor neuron injury relevant to ALS.—Pedersen W. W., Luo H., Kruman, I., Kasarskis, E., Mattson, M. P. The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis.

Key Words: NSC-19 • oxidative stress • spinal cord • superoxide dismutase • transgenic mice

This article has been cited by other articles:

				J. Xie and Q. Guo Apoptosis Antagonizing Transcription Factor Protects Renal Tubule Cells against Oxidative Damage and Apoptosis Induced by Ischemia-Reperfusion J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3336 - 3346. [Abstract] [Full Text] [PDF]

				E. B. Affar, M. Po-shan Luke, F. Gay, D. Calvo, G. Sui, R. S. Weiss, E. Li, and Y. Shi Targeted ablation of par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents. Cancer Res., April 1, 2006; 66(7): 3456 - 3462. [Abstract] [Full Text] [PDF]

				M. P. Mattson and M. Gleichmann The Neuronal Death Protein Par-4 Mediates Dopaminergic Synaptic Plasticity Mol. Interv., October 1, 2005; 5(5): 278 - 281. [Abstract] [Full Text] [PDF]

				K. Fukada, F. Zhang, A. Vien, N. R. Cashman, and H. Zhu Mitochondrial Proteomic Analysis of a Cell Line Model of Familial Amyotrophic Lateral Sclerosis Mol. Cell. Proteomics, December 1, 2004; 3(12): 1211 - 1223. [Abstract] [Full Text] [PDF]

				J. Xie and Q. Guo Par-4 Inhibits Choline Uptake by Interacting with CHT1 and Reducing Its Incorporation on the Plasma Membrane J. Biol. Chem., July 2, 2004; 279(27): 28266 - 28275. [Abstract] [Full Text] [PDF]

				Q. Guo and J. Xie AATF Inhibits Aberrant Production of Amyloid {beta} Peptide 1-42 by Interacting Directly with Par-4 J. Biol. Chem., February 6, 2004; 279(6): 4596 - 4603. [Abstract] [Full Text] [PDF]

				Q. Guo Cyclin-Dependent Kinase 5--A Neuronal Killer? Sci. Aging Knowl. Environ., December 17, 2003; 2003(50): pe36 - 36. [Abstract] [Full Text]

				N. El-Guendy, Y. Zhao, S. Gurumurthy, R. Burikhanov, and V. M. Rangnekar Identification of a Unique Core Domain of Par-4 Sufficient for Selective Apoptosis Induction in Cancer Cells Mol. Cell. Biol., August 15, 2003; 23(16): 5516 - 5525. [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]

				W. A. Pedersen, R. Wan, P. Zhang, and M. P. Mattson Urocortin, But Not Urocortin II, Protects Cultured Hippocampal Neurons from Oxidative and Excitotoxic Cell Death via Corticotropin-Releasing Hormone Receptor Type I J. Neurosci., January 15, 2002; 22(2): 404 - 412. [Abstract] [Full Text] [PDF]