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

J. Biol. Chem., Vol. 280, Issue 27, 25571-25579, July 8, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/27/25571    most recent M501920200v1 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 Vargas, M. R. Articles by Barbeito, L. Search for Related Content PubMed PubMed Citation Articles by Vargas, M. R. Articles by Barbeito, L. Social Bookmarking                      What's this?

Fibroblast Growth Factor-1 Induces Heme Oxygenase-1 via Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) in Spinal Cord Astrocytes

CONSEQUENCES FOR MOTOR NEURON SURVIVAL^*

Marcelo R. Vargas, Mariana Pehar, Patricia Cassina, Laura Martínez-Palma, John A. Thompson¶, Joseph S. Beckman||, and Luis Barbeito**

From the Departamento de Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay, the Departamento de Histología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay, the^¶ Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, and the^|| Linus Pauling Institute, Environmental Health Sciences Center, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331

Fibroblast growth factor-1 (FGF-1) is highly expressed in motor neurons and can be released in response to sublethal cell injury. Because FGF-1 potently activates astroglia and exerts a direct neuroprotection after spinal cord injury or axotomy, we examined whether it regulated the expression of inducible and cytoprotective heme oxygenase-1 (HO-1) enzyme in astrocytes. FGF-1 induced the expression of HO-1 in cultured rat spinal cord astrocytes, which was dependent on FGF receptor activation and prevented by cycloheximide. FGF-1 also induced Nrf2 mRNA and protein levels and prompted its nuclear translocation. HO-1 induction was abolished by transfection of astrocytes with a dominant-negative mutant Nrf2, indicating that FGF-1 regulates HO-1 expression through Nrf2. FGF-1 also modified the expression of other antioxidant genes regulated by Nrf2. Both Nrf2 and HO-1 levels were increased and co-localized with reactive astrocytes in the degenerating lumbar spinal cord of rats expressing the amyotrophic lateral sclerosis-linked SOD1 G93A mutation. Overexpression of Nrf2 in astrocytes increased survival of co-cultured embryonic motor neurons and prevented motor neuron apoptosis mediated by nerve growth factor through p75 neurotrophin receptor. Taken together, these results emphasize the key role of astrocytes in determining motor neuron fate in amyotrophic lateral sclerosis.

Received for publication, February 22, 2005 , and in revised form, April 13, 2005.

^* This work was supported by Fogarty International Research Collaboration Award (FIRCA) Grant RO3TW006482 (to J. S. B. and L. B), Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), the Linus Pauling Institute, and Environmental Health Sciences Center Grant ES00210 from the Oregon State University. 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: Instituto Clemente Estable. Av. Italia 3318-11600, Montevideo, Uruguay. Tel.: 598-2-487-16-16; E-mail: lbarb{at}iibce.edu.uy.

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

This article has been cited by other articles:

				C. J. Baglole, P. J. Sime, and R. P. Phipps Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L624 - L636. [Abstract] [Full Text] [PDF]

				F. Lu, M. Zahid, C. Wang, M. Saeed, E. L. Cavalieri, and E. G. Rogan Resveratrol Prevents Estrogen-DNA Adduct Formation and Neoplastic Transformation in MCF-10F Cells Cancer Prevention Research, July 1, 2008; 1(2): 135 - 145. [Abstract] [Full Text] [PDF]

				P. Cassina, A. Cassina, M. Pehar, R. Castellanos, M. Gandelman, A. de Leon, K. M. Robinson, R. P. Mason, J. S. Beckman, L. Barbeito, et al. Mitochondrial Dysfunction in SOD1G93A-Bearing Astrocytes Promotes Motor Neuron Degeneration: Prevention by Mitochondrial-Targeted Antioxidants J. Neurosci., April 16, 2008; 28(16): 4115 - 4122. [Abstract] [Full Text] [PDF]

				J. Dulak, J. Deshane, A. Jozkowicz, and A. Agarwal Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology: Focus on Angiogenesis Circulation, January 15, 2008; 117(2): 231 - 241. [Abstract] [Full Text] [PDF]

				L. Ferraiuolo, P. R. Heath, H. Holden, P. Kasher, J. Kirby, and P. J. Shaw Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS J. Neurosci., August 22, 2007; 27(34): 9201 - 9219. [Abstract] [Full Text] [PDF]

				E. Tassi, S. Walter, A. Aigner, R. H. Cabal-Manzano, R. Ray, P. J. Reier, and A. Wellstein Effects on neurite outgrowth and cell survival of a secreted fibroblast growth factor binding protein upregulated during spinal cord injury Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R775 - R783. [Abstract] [Full Text] [PDF]

				P. S. Lecane, M. W. Karaman, M. Sirisawad, L. Naumovski, R. A. Miller, J. G. Hacia, and D. Magda Motexafin Gadolinium and Zinc Induce Oxidative Stress Responses and Apoptosis in B-Cell Lymphoma Lines Cancer Res., December 15, 2005; 65(24): 11676 - 11688. [Abstract] [Full Text] [PDF]