Skip Navigation



Brain Advance Access published online on April 7, 2005
Brain, doi:10.1093/brain/awh492
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
128/7/1613    most recent
awh492v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Coma, M.
Right arrow Articles by Muñoz, F. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coma, M.
Right arrow Articles by Muñoz, F. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received November 11, 2004
Revised February 14, 2005
Accepted March 1, 2005

Article

Lack of oestrogen protection in amyloid-mediated endothelial damage due to protein nitrotyrosination

M. Coma 1, F. X. Guix 2, I. Uribesalgo 1, G. Espuña 3, M. Solé 1, D. Andreu 3, and F. J. Muñoz 1*

1 Laboratori de Fisiologia Molecular, Unitat de Senyalització Cellular, Universitat Pompeu Fabra, Barcelona, Spain
2 Laboratori de Fisiologia Molecular, Unitat de Senyalització Cellular, Universitat Pompeu Fabra, Barcelona, Spain; Unitat de Proteòmica, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
3 Unitat de Proteòmica, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

* To whom correspondence should be addressed.
F. J. Muñoz, E-mail: paco.munoz{at}upf.edu


  Abstract

Amyloid {beta}-peptide (A{beta}) cytotoxicity, the hallmark of Alzheimer's disease, implicates oxidative stress in both neurons and vascular cells, particularly endothelial cells. Consequently, antioxidants have shown neuroprotective activities against A{beta}-induced cytotoxicity. Among the different antioxidants used in both in vitro and in vivo studies, 17{beta}-oestradiol (E2) has garnered the most attention. Oestrogen attenuated A{beta}E22Q-induced toxicity in neurons but failed to protect endothelial cells. Here we show that E2-mediated activation of endothelial nitric oxide synthase (eNOS) increases the production of nitric oxide (NO), which, under A{beta}E22Q-induced oxidative damage, results in the formation of peroxynitrite and increased nitration of tyrosine residues. Inhibition of eNOS prevents nitrotyrosination and permits E2-mediated protection against A{beta}E22Q on endothelial cells. The main nitrotyrosinated proteins in the presence of E2 and A{beta}E22Q were identified by MALDI-TOF mass spectrometry. These proteins are key players in the regulation of energy production, cytoskeletal integrity, protein metabolism and protection against oxidative stress. Our data highlight the potential damaging consequences of E2 in vascular disorders dealing with oxidative stress conditions, such as cerebral amyloid angiopathy, stroke and ischaemia-reperfusion conditions.

Keywords: Alzheimer's disease; amyloid {beta}-peptide; oestrogen; nitric oxide; nitrotyrosination.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NeurologyHome page
R. D. Abbott, L. J. Launer, B. L. Rodriguez, G. W. Ross, P.W.F. Wilson, K. H. Masaki, D. Strozyk, J. D. Curb, K. Yano, J. S. Popper, et al.
Serum estradiol and risk of stroke in elderly men
Neurology, February 20, 2007; 68(8): 563 - 568.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
P. Pacher, J. S. Beckman, and L. Liaudet
Nitric Oxide and Peroxynitrite in Health and Disease
Physiol Rev, January 1, 2007; 87(1): 315 - 424.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. L. Masters and K. Beyreuther
Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the A{beta} amyloid pathway
Brain, November 1, 2006; 129(11): 2823 - 2839.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
C. Bolego, E. Vegeto, C. Pinna, A. Maggi, and A. Cignarella
Selective Agonists of Estrogen Receptor Isoforms: New Perspectives for Cardiovascular Disease
Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2192 - 2199.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. Vegeto, S. Belcredito, S. Ghisletti, C. Meda, S. Etteri, and A. Maggi
The Endogenous Estrogen Status Regulates Microglia Reactivity in Animal Models of Neuroinflammation
Endocrinology, May 1, 2006; 147(5): 2263 - 2272.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.