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

J. Biol. Chem., Vol. 279, Issue 37, 39155-39164, September 10, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/37/39155    most recent M405456200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, Y. Articles by Zhang, J. Search for Related Content PubMed PubMed Citation Articles by Zhou, Y. Articles by Zhang, J. Social Bookmarking                      What's this?

Analysis of -Synuclein-associated Proteins by Quantitative Proteomics^*

Yong Zhou, Guangyu Gu, David R. Goodlett, Terry Zhang¶, Catherine Pan, Thomas J. Montine, Kathleen S. Montine, Ruedi H. Aebersold||, and Jing Zhang**

From the Departments of Pathology and Medicinal Chemistry, University of Washington School of Medicine, Seattle, Washington 98104, the ^||Institute of Systems Biology, Seattle, Washington 98103, and the ^¶Thermo Electron Corporation, San Jose, California 95134

To identify the proteins associated with soluble -synuclein (AS) that might promote AS aggregation, a key event leading to neurodegeneration, we quantitatively compared protein profiles of AS-associated protein complexes in MES cells exposed to rotenone, a pesticide that produces parkinsonism in animals and induces Lewy body (LB)-like inclusions in the remaining dopaminergic neurons, and to vehicle. We identified more than 250 proteins associated with Nonidet P-40 soluble AS, and demonstrated that at least 51 of these proteins displayed significant differences in their relative abundance in AS complexes under conditions where rotenone was cytotoxic and induced formation of cytoplasmic inclusions immunoreactive to anti-AS. Overexpressing one of these proteins, heat shock protein (hsp) 70, not only protected cells from rotenone-mediated cytotoxicity but also decreased soluble AS aggregation. Furthermore, the protection afforded by hsp70 transfection appeared to be related to suppression of rotenone-induced oxidative stress as well as mitochondrial and proteasomal dysfunction.

Received for publication, May 17, 2004 , and in revised form, June 28, 2004.

^* This work was supported by National Institutes of Health Grants ES10196 (to T. J. M.) and ES05842 and ES12703 (to J. Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplementary Materials.

Both authors contributed equally to this work.

^** To whom correspondence should be addressed: Division of Neuropathology, University of Washington School of Medicine, Box 359635, Harborview Medical Center, Seattle, WA 98104. Tel.: 206-341-5245; Fax: 206-341-5249; E-mail: zhangj{at}u.washington.edu.

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

This article has been cited by other articles:

				S. Hamamichi, R. N. Rivas, A. L. Knight, S. Cao, K. A. Caldwell, and G. A. Caldwell Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model PNAS, January 15, 2008; 105(2): 728 - 733. [Abstract] [Full Text] [PDF]

				J. Jin, G. J. Li, J. Davis, D. Zhu, Y. Wang, C. Pan, and J. Zhang Identification of Novel Proteins Associated with Both {alpha}-Synuclein and DJ-1 Mol. Cell. Proteomics, May 1, 2007; 6(5): 845 - 859. [Abstract] [Full Text] [PDF]

				Y. Kinoshita, T. Uo, S. Jayadev, G. A. Garden, T. P. Conrads, T. D. Veenstra, and R. S. Morrison Potential Applications and Limitations of Proteomics in the Study of Neurological Disease Arch Neurol, December 1, 2006; 63(12): 1692 - 1696. [Full Text] [PDF]

				J. A. Marsh, V. K. Singh, Z. Jia, and J. D. Forman-Kay Sensitivity of secondary structure propensities to sequence differences between {alpha}- and {gamma}-synuclein: Implications for fibrillation Protein Sci., December 1, 2006; 15(12): 2795 - 2804. [Abstract] [Full Text] [PDF]

				A. M. Boutte, R. L. Woltjer, L. J. Zimmerman, S. L. Stamer, K. S. Montine, M. V. Manno, P. J. Cimino, D. C. Liebler, and T. J. Montine Selectively increased oxidative modifications mapped to detergent-insoluble forms of A{beta} and {beta}-III tubulin in Alzheimer's disease FASEB J, July 1, 2006; 20(9): 1473 - 1483. [Abstract] [Full Text] [PDF]

				J. Jin, C. Hulette, Y. Wang, T. Zhang, C. Pan, R. Wadhwa, and J. Zhang Proteomic Identification of a Stress Protein, Mortalin/mthsp70/GRP75: Relevance To Parkinson Disease Mol. Cell. Proteomics, July 1, 2006; 5(7): 1193 - 1204. [Abstract] [Full Text] [PDF]

				M. A. Utton, W. J. Noble, J. E. Hill, B. H. Anderton, and D. P. Hanger Molecular motors implicated in the axonal transport of tau and {alpha}-synuclein J. Cell Sci., October 15, 2005; 118(20): 4645 - 4654. [Abstract] [Full Text] [PDF]

				Y. Zhou, Y. Wang, M. Kovacs, J. Jin, and J. Zhang Microglial Activation Induced by Neurodegeneration: A Proteomic Analysis Mol. Cell. Proteomics, October 1, 2005; 4(10): 1471 - 1479. [Abstract] [Full Text] [PDF]

				F. Tribl, M. Gerlach, K. Marcus, E. Asan, T. Tatschner, T. Arzberger, H. E. Meyer, G. Bringmann, and P. Riederer "Subcellular Proteomics" of Neuromelanin Granules Isolated from the Human Brain Mol. Cell. Proteomics, July 1, 2005; 4(7): 945 - 957. [Abstract] [Full Text] [PDF]

				P. K. Auluck, M. C. Meulener, and N. M. Bonini Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila J. Biol. Chem., January 28, 2005; 280(4): 2873 - 2878. [Abstract] [Full Text] [PDF]