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

J. Biol. Chem., Vol. 280, Issue 10, 9604-9609, March 11, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/10/9604    most recent M409447200v1 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 Google Scholar Google Scholar Articles by Fuenzalida, K. M. Articles by Bronfman, M. Search for Related Content PubMed PubMed Citation Articles by Fuenzalida, K. M. Articles by Bronfman, M. Social Bookmarking                      What's this?

Peroxisome Proliferator-activated Receptor Is a Novel Target of the Nerve Growth Factor Signaling Pathway in PC12 Cells^*

Karen M. Fuenzalida, Mauricio C. Aguilera, Daniela G. Piderit, Patricio C. Ramos, David Contador, Verónica Quiñones, Atilio Rigotti, Francisca C. Bronfman, and Miguel Bronfman¶

From the Centro de Regulación Celular y Patología and Millennium Institute for Fundamental and Applied Biology, Faculty of Biological Sciences and Department of Gastroenterology, Faculty of Medicine, P. Universidad Católica de Chile, Casilla 114-D, Santiago, Chile

Peroxisome proliferator-activated receptor (PPAR), a member of the nuclear receptor superfamily, is subject to considerable interest because of its role in adipocyte differentiation, metabolic control, and anti-inflammatory action. PPAR research in brain cells is presently focused on glial PPAR because of its potential as a pharmacological target in the treatment of neurodegenerative diseases with an inflammatory component. In neurons PPAR function is far from clear, and PPAR agonist-dependent and -independent effects on cell survival or differentiation have been reported. We used PC12 cells, widely used to study neuronal signaling, such as nerve growth factor (NGF)-induced differentiation and survival or epidermal growth factor-dependent cell proliferation to dissect the possible involvement of PPAR in these pathways. We show that NGF but not epidermal growth factor increases the transcriptional activity of PPAR, and modulates the expression of this transcription factor. Because NGF signals through the tyrosine kinase (TrkA) NGF receptor and/or the p75^NTR receptor, we used rescue experiments with a PC12 cell mutant lacking TrkA to show that NGF-induced PPAR activation is dependent on TrkA activation. Our results point out PPAR as a novel target of the TrkA-mediated neuronal cell survival and differentiating pathway and suggest a potential new inflammatory-independent therapeutic approach for pharmacological intervention in neurological disorders.

Received for publication, August 17, 2004 , and in revised form, December 20, 2004.

^* 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.

^¶ To whom correspondence should be addressed: Dept. of Cellular and Molecular Biology, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile Casilla 114-D Santiago, Chile. Tel.: 56-2-686-2833; Fax: 56-2-635-2599; E-mail: mbronfma{at}bio.puc.cl.

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