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

J. Biol. Chem., Vol. 283, Issue 24, 16808-16817, June 13, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/24/16808    most recent M709014200v1 Submit a Letter to Editor 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tessari, I. Articles by Bubacco, L. Search for Related Content PubMed PubMed Citation Articles by Tessari, I. Articles by Bubacco, L. Social Bookmarking                      What's this?

The Reaction of -Synuclein with Tyrosinase

POSSIBLE IMPLICATIONS FOR PARKINSON DISEASE^*

Isabella Tessari, Marco Bisaglia, Francesco Valle, Bruno Samorì, Elisabetta Bergantino, Stefano Mammi^¶, and Luigi Bubacco¹

From the Departments of Biology and ^¶Chemical Sciences, University of Padova, Padova 35121 and the Department of Biochemistry, University of Bologna, Bologna 40126, Italy

Oxidative stress appears to be directly involved in the pathogenesis of Parkinson disease. Several different pathways have been identified for the production of oxidative stress conditions in nigral dopaminergic neurons, including a pathological accumulation of cytosolic dopamine with the subsequent production of toxic reactive oxygen species or the formation of highly reactive quinone species. On these premises, tyrosinase, a key copper enzyme known for its role in the synthesis of melanin in skin and hair, has been proposed to take part in the oxidative chemistry related to Parkinson disease. A study is herein presented of the in vitro reactivity of tyrosinase with -synuclein, aimed at defining the molecular basis of their synergistic toxic effect. The results presented here indicate that, in conformity with the stringent specificity of tyrosinase, the exposed tyrosine side-chains are the reactive centers of -synuclein. The reactivity of -synuclein depends on whether it is free or membrane bound, and the chemical modifications on the tyrosinase-treated -synuclein strongly influence its aggregation properties. On the basis of our results, we propose a cytotoxic model which includes a possible new toxic role for -synuclein exacerbated by its direct chemical modification by tyrosinase.

Received for publication, November 2, 2007 , and in revised form, March 26, 2008.

^* This work was supported by the Progetti di Rilevante Interesse Nazionale and the Fondo per gli Investimenti della Ricerca di Base. 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 supplemental Figs. S1 and S2.

¹ To whom correspondence should be addressed: Tel.: 39-049-827-6346; Fax: 39-049-827-6300; E-mail: luigi.bubacco{at}unipd.it.

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