Skip Navigation


Human Molecular Genetics Advance Access originally published online on March 6, 2007
Human Molecular Genetics 2007 16(9):1039-1050; doi:10.1093/hmg/ddm049
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/9/1039    most recent
ddm049v1
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Porta, S.
Right arrow Articles by Martí, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Porta, S.
Right arrow Articles by Martí, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration

Sílvia Porta1,{dagger}, Selma A. Serra3,{dagger}, Meritxell Huch1, Miguel A. Valverde3, Franc Llorens2, Xavier Estivill1, Maria L. Arbonés1 and Eulàlia Martí1,*

1 Genes and Disease Program, 2 Bioinformatics and Genomics Program, Center for Genomic Regulation (CRG-UPF), Biomedical Research Park Building, E-08003 Barcelona, Catalonia, Spain and 3 Molecular Physiology and Channelopathies, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain

* To whom correspondence should be addressed at: Genes and Disease Program, Genomic Regulation Center (CRG-UPF), Biomedical Research Park, C/Dr Aiguader 88, E-08003 Barcelona, Catalonia, Spain. Tel: +34 933160201; Fax: +34 933160099; Email: eulalia.marti{at}crg.es

Received November 27, 2006; Revised February 19, 2007; Accepted February 28, 2007

Oxidative stress (OS) underlies neuronal dysfunction in many neurodegenerative disorders. Regulator of Calcineurin 1 (RCAN1 or DSCR1) is a dose-sensitive gene whose overexpression has been linked to Down syndrome (DS) and Alzheimer's disease (AD) neuropathology and to the response of cells to stress stimuli. Here, we show that RCAN1 mRNA and protein expression are sensitive to OS in primary neurons, and we evaluate the involvement of RCAN1 dosage in neuronal death induced by OS. We find that Rcan1–/– neurons display an increased resistance to damage by H2O2, which can be reverted by RCAN1 overexpression or by exogenous inhibitors of calcineurin. Although increased intracellular Ca2+ concentration is an important factor in OS-mediated cell death, our results show that Ca2+ loading after exposure to H2O2 was similar in Rcan1+/+ and Rcan1–/– neurons. Our data further suggest that CaN and NFAT signaling protect against OS in both Rcan1+/+ and Rcan1–/– neurons. To explain the observed differential vulnerability, we therefore propose a mechanism downstream of H2O2-mediated Ca2+ entry, involving calcineurin-NFAT signaling. These findings highlight the importance of RCAN1 gene dosage in the modulation of cell survival and death pathways and suggest that changes in the amount of RCAN1 could represent an important mechanism for regulating susceptibility to neurodegeneration, especially in DS and AD.

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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
 Hum Mol GenetHome page
D. J. Keating, D. Dubach, M. P. Zanin, Y. Yu, K. Martin, Y.-F. Zhao, C. Chen, S. Porta, M. L. Arbones, L. Mittaz, et al.
DSCR1/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: implications for Down syndrome and Alzheimer's disease
Hum. Mol. Genet., April 1, 2008; 17(7): 1020 - 1030.
[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.