English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/24671
Compartir / Impacto:
Add this article to your Mendeley library MendeleyBASE
Citado 26 veces en Web of Knowledge®  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL

Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I

AutorFrago, Laura M.; Cañon, Susana; De la Rosa, Enrique J. ; León, Yolanda; Varela-Nieto, Isabel
Palabras claveP75 neurotrophin receptor (p75NTR)
Caspase activation
Cell survival
Otic vesicle
Fecha de publicación1-feb-2003
EditorCompany of Biologists
CitaciónJournal of Cell Science 116(3): 475-486 (2003)
ResumenNerve growth factor induces cell death in organotypic cultures of otic vesicle explants. This cell death has a restricted pattern that reproduces the in vivo pattern of apoptosis occurring during inner ear development. In this study, we show that binding of nerve growth factor to its low affinity p75 neurotrophin receptor is essential to achieve the apoptotic response. Blockage of binding to p75 receptor neutralized nerve-growth-factor-induced cell death, as measured by immunoassays detecting the presence of cytosolic oligonucleosomes and by TUNEL assay to visualize DNA fragmentation. Nerve growth factor also induced a number of cell-death-related intracellular events including ceramide generation, caspase activation and poly-(ADP ribose) polymerase cleavage. Again, p75 receptor blockade completely abolished all of these effects. Concerning the intracellular pathway, ceramide increase depended on initiator caspases, whereas its actions depended on both initiator and effector caspases, as shown by using site-specific caspase inhibitors. Conversely, insulin-like growth factor I, which promotes cell growth and survival in the inner ear, abolished apoptosis induced by nerve growth factor. Insulin-like growth factor cytoprotective actions were accomplished, at least in part, by decreasing endogenous ceramide levels and activating Akt. Taken together, these results strongly suggest that regulation of nerve-growth-factor-induced apoptosis in the otocysts occurs via p75 receptor binding and is strictly controlled by the interaction with survival signalling pathways.
Descripción12 pages, 6 figures, 4 tables.
Versión del editorhttp://dx.doi.org/10.1242/jcs.00223
Aparece en las colecciones: (IIBM) Artículos
(CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Programmed cell death.pdf928,42 kBAdobe PDFVista previa
Mostrar el registro completo

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