Endogenous XIAP but no other members of the inhibitory apoptosis protein family modulates cerebellar granule neurons survival
Blancas, Sugela (Universidad Nacional Autónoma de México. Instituto de Fisiología Celular)
Fadó, Rut (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rodríguez Álvarez, José (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Morán, Julio (Universidad Nacional Autónoma de México. Instituto de Fisiología Celular)

Fecha:	2014
Resumen:	Programmed cell death plays a critical role during cerebellar development. In particular, it has been shown in vivo and in vitro that developing cerebellar granule neurons (CGN) die apoptotically. Apoptosis involves a series of morphological changes and the activation of caspases. Inhibitor of apoptosis proteins (IAPs) is implicated in negative regulation of caspase activation and apoptotic cell death. Although apoptotic death of CGN has been extensively studied, there is no information about the role of IAPs in the developing cerebellum. Here, we studied the participation of some members of IAPs in the survival of the developing rat CGN in culture and under physiological conditions. Under these conditions, we found a differential expression pattern of cIAP-1, cIAP-2, XIAP and survivin during cerebellar development in an age-dependent manner, highlighting the significant increase of XIAP levels. We also detected an interaction between XIAP and caspase 3 at postnatal day (P) 12 and 16. On the other hand, we found a significant decrease of XIAP levels in cultured CGN maintained in chronic potassium deprivation, an apoptotic condition, suggesting a possible relationship between XIAP levels and neuronal viability. Under these conditions, we also detected the interaction of XIAP with active caspase-3. The down-regulation of XIAP in CGN cultured under survival conditions (chronic potassium depolarization) induced a reduction of cell viability and an increment of apoptotic cells. These findings support the idea that IAPs could be involved in the survival of CGN and that XIAP might be critical for neuronal survival in cerebellar development and during chronic depolarization in cultured CGN through a mechanism involving caspase inhibition.
Ayudas:	Ministerio de Ciencia e Innovación SAF2008-01904 Instituto de Salud Carlos III RD06/0026/1009 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-1231
Nota:	Altres ajuts: DGAPA-PAPIIT-UNAM (IN206213) i CONACYT (179234)
Nota:	Altres ajuts: CIBERNED/CB06/05/0042
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Materia:	Apoptotic-like death ; IAPs ; Caspases ; Cerebellum development ; Cerebellar granule neurons ; Potassium deprivation
Publicado en:	International Journal of Developmental Neuroscience, Vol. 37 (October 2014) , p. 26-35, ISSN 1873-474X

DOI: 10.1016/j.ijdevneu.2014.06.006

Post-print 34 p, 2.4 MB

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