English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/81709
Share/Impact:
Statistics
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:
Title

Levels of protein tyrosine phosphatase 1B determine susceptibility to apoptosis in serum-deprived hepatocytes

AuthorsGonzález-Rodríguez, Águeda; Escribano, Óscar; Alba, Javier; Rondinone, Cristina M.; Benito, Manuel; Valverde, Ángela M.
Issue Date2007
PublisherWiley-Blackwell
CitationJournal of Cellular Physiology 212(1): 76-88 (2007)
AbstractProtein tyrosine phosphatase 1B (PTP1B) is a negative regulator of tyrosine kinase growth factor signaling. To assess the importance of PTP1B in the balance between death and survival in the liver, we have developed immortalized neonatal hepatocyte cell lines lacking (PTP1B-/-) or overexpressing (PTP1B+/+PTP1B) PTP1B. Early activation of caspase-3 occurred in PTP1B+/+PTP1B hepatocytes but was nearly abolished in PTP1B -/- cells. At the molecular level, PTP1B overexpression/deficiency altered the balance of pro-(Bim) and anti-(Bcl-xL) apoptotic members of the Bcl-2 fmily upon serum withdrawal. Likewise, cytosolic cytochrome C increased rapidly in PTP1B+/+PTP1B hepatocytes whereas it was retained in the mitochondria of PTPIB-/- cells. DNA fragmentation and the increase of apoptotic cells induced by serum withdrawal in wild-type (PTP1B+/+) hepatocytes were absent in PTP1B-/- cells. Conversely, overexpression of PTP1B accelerated DNA laddering and increased the number of apoptotic cells. In serum-deprived PTP1B+/+PTP1B hepatocytes, a rapid entry of Foxo1 into the nucleus and an earlier activation of caspase-8 was observed. However, both events were suppressed in PTP1B -/- hepatocytes. Moreover, PTP1B deficiency conferred resistance to apoptosis induced by activation of Fas and constitutively active Foxo1. Rescue of PTP 1B in deficient hepatocytes recovered the phenotype of wild-type cells whereas reduction of PTP1B by siRNA suppressed apoptosis. Our results reveal a unique role for PTP1B as a mediator of the apoptotic pathways triggered by trophic factors withdrawal in hepatocytes. This novel mechanism may represent an important target in the design of therapeutic strategies for human liver regeneration after pathological damage as well as for treatment of hepatocarcinomas. © 2007 Wiley-Liss, Inc.
URIhttp://hdl.handle.net/10261/81709
DOI10.1002/jcp.21004
Identifiersdoi: 10.1002/jcp.21004
issn: 0021-9541
e-issn: 1097-4652
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.