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) All Versions of this Article: M500090-MCP200v1 4/12/1849    most recent Submit a response 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perluigi, M. Articles by Butterfield, D. A. Search for Related Content PubMed PubMed Citation Articles by Perluigi, M. Articles by Butterfield, D. A. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 4:1849-1861, 2005.
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Proteomic Analysis of Protein Expression and Oxidative Modification in R6/2 Transgenic Mice

A Model of Huntington Disease^*

From the ^aDepartment of Biochemical Sciences, University of Rome "La Sapienza," 00185 Rome, Italy, ^bDepartment of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, ^cDepartment of Neurology, ^dAnatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536-0305, ^eKidney Disease Program and Core Proteomics Laboratory and ^fDepartment of Pharmacology, University of Louisville School of Medicine and Veterans Affairs Medical Center, Louisville, Kentucky 40292, ^gDepartment of Chemistry, Section of Biochemistry, University of Catania, 95100 Catania, Italy, ^hCenter of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506-0059, and ⁱSanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536

Huntington disease (HD) is a hereditary neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. The genetic defect responsible for the onset of the disease, expansion of CAG repeats in exon 1 of the gene that codes for huntingtin on chromosome 4, has been unambiguously identified. On the other hand, the mechanisms by which the mutation causes the disease are not completely understood yet. However, defects in energy metabolism of affected cells may cause oxidative damage, which has been proposed as one of the underlying molecular mechanisms that participate in the etiology of the disease. In our effort to investigate the extent of oxidative damage occurring at the protein level, we used a parallel proteomic approach to identify proteins potentially involved in processes upstream or downstream of the disease-causing huntingtin in a well established HD mouse model (R6/2 transgenic mice). We have demonstrated that the expression levels of dihydrolipoamide S-succinyltransferase and aspartate aminotransferase increase consistently over the course of disease (10-week-old mice). In contrast, pyruvate dehydrogenase expression levels were found to be decreased in 10-week-old HD transgenic mice compared with young (4-week-old) mice. Our experimental approach also led to the identification of oxidatively modified proteins. Six proteins were found to be significantly oxidized in old R6/2 transgenic mice compared with either young transgenic mice or non-transgenic mice. These proteins are -enolase, -enolase (neuron-specific enolase), aconitase, the voltage-dependent anion channel 1, heat shock protein 90, and creatine kinase. Because oxidative damage has proved to play an important role in the pathogenesis and the progression of Huntington disease, our results for the first time identify specific oxidatively modified proteins that potentially contribute to the pathogenesis of Huntington disease.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Zabel, L. Mao, B. Woodman, M. Rohe, M. A. Wacker, Y. Klare, A. Koppelstatter, G. Nebrich, O. Klein, S. Grams, et al. A Large Number of Protein Expression Changes Occur Early in Life and Precede Phenotype Onset in a Mouse Model for Huntington Disease Mol. Cell. Proteomics, April 1, 2009; 8(4): 720 - 734. [Abstract] [Full Text] [PDF]

				J. N. Savas, A. Makusky, S. Ottosen, D. Baillat, F. Then, D. Krainc, R. Shiekhattar, S. P. Markey, and N. Tanese Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies PNAS, August 5, 2008; 105(31): 10820 - 10825. [Abstract] [Full Text] [PDF]

				A. Zourlidou, T. Gidalevitz, M. Kristiansen, C. Landles, B. Woodman, D. J. Wells, D. S. Latchman, J. de Belleroche, S. J. Tabrizi, R. I. Morimoto, et al. Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation Hum. Mol. Genet., May 1, 2007; 16(9): 1078 - 1090. [Abstract] [Full Text] [PDF]

				M.-C. Chiang, C.-G. Juo, H.-H. Chang, H.-M. Chen, E. C. Yi, and Y. Chern Systematic Uncovering of Multiple Pathways Underlying the Pathology of Huntington Disease by an Acid-cleavable Isotope-coded Affinity Tag Approach Mol. Cell. Proteomics, May 1, 2007; 6(5): 781 - 797. [Abstract] [Full Text] [PDF]

				E. Easlon, F. Tsang, I. Dilova, C. Wang, S.-P. Lu, C. Skinner, and S.-J. Lin The Dihydrolipoamide Acetyltransferase Is a Novel Metabolic Longevity Factor and Is Required for Calorie Restriction-mediated Life Span Extension J. Biol. Chem., March 2, 2007; 282(9): 6161 - 6171. [Abstract] [Full Text] [PDF]