English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/14153
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Estradiol Activates β-Catenin Dependent Transcription in Neurons

AutorVarea, Olga ; Garrido Jurado, Juan José ; Dopazo, Ana; García-Segura, Luis M. ; Wandosell, Francisco ; Méndez, Pablo
Palabras claveEstradiol
Fecha de publicación10-abr-2009
EditorPublic Library of Science
CitaciónPLoS ONE. 2009; 4(4): e5153.
ResumenEstradiol may fulfill a plethora of functions in neurons, in which much of its activity is associated with its capacity to directly bind and dimerize estrogen receptors. This hormone-protein complex can either bind directly to estrogen response elements (ERE's) in gene promoters, or it may act as a cofactor at non-ERE sites interacting with other DNA-binding elements such as AP-1 or c-Jun. Many of the neuroprotective effects described for estrogen have been associated with this mode of action. However, recent evidence suggests that in addition to these “genomic effects”, estrogen may also act as a more general “trophic factor” triggering cytoplasmic signals and extending the potential activity of this hormone. We demonstrated that estrogen receptor alpha associates with β-catenin and glycogen synthase kinase 3 in the brain and in neurons, which has since been confirmed by others. Here, we show that the action of estradiol activates β-catenin transcription in neuroblastoma cells and in primary cortical neurons. This activation is time and concentration-dependent, and it may be abolished by the estrogen receptor antagonist ICI 182780. The transcriptional activation of β-catenin is dependent on lymphoid enhancer binding factor-1 (LEF-1) and a truncated-mutant of LEF-1 almost completely blocks estradiol TCF-mediated transcription. Transcription of a TCF-reporter in a transgenic mouse model is enhanced by estradiol in a similar fashion to that produced by Wnt3a. In addition, activation of a luciferase reporter driven by the engrailed promoter with three LEF-1 repeats was mediated by estradiol. We established a cell line that constitutively expresses a dominant-negative LEF-1 and it was used in a gene expression microarray analysis. In this way, genes that respond to estradiol or Wnt3a, sensitive to LEF-1, could be identified and validated. Together, these data demonstrate the existence of a new signaling pathway controlled by estradiol in neurons. This pathway shares some elements of the insulin-like growth factor-1/Insulin and Wnt signaling pathways, however, our data strongly suggest that it is different from that of both these ligands. These findings may reveal a set of new physiological roles for estrogens, at least in the Central Nervous System (CNS).
Descripción24 pages, 9 figures, 1 table.-- Supporting information available: Figure S1, doi:10.1371/journal.pone.0005153.s001 (9.68 MB EPS); Figure S2, doi:10.1371/journal.pone.0005153.s002 (2.36 MB EPS); Figure S3, doi:10.1371/journal.pone.0005153.s003 (1.61 MB EPS), Figure S4, doi:10.1371/journal.pone.0005153.s004 (2.50 MB EPS).
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0004983
Aparece en las colecciones: (CBM) Artículos
(IC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
pone.0005153.pdf2,49 MBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.