title: Endogenous XIAP, but not other members of the inhibitory apoptosis protein family modulates cerebellar granule neurons survival.
abstract: 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.
authors: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, Mexico. Electronic address: sugela.blancas@ipicyt.edu.mx.
authors: Sugela
authors: S
authors: Blancas
authors: Institut de Neurociències and Dpt. Bioquímica i Biología Molecular, UniversitatAutònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: Rut.Fado@uab.cat.
authors: Rut
authors: R
authors: Fadó
authors: Institut de Neurociències and Dpt. Bioquímica i Biología Molecular, UniversitatAutònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: Jose.Rodriguez@uab.es.
authors: José
authors: J
authors: Rodriguez-Alvarez
authors: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, Mexico. Electronic address: jmoran@ifc.unam.mx.
authors: Julio
authors: J
authors: Morán
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D016086:Lentivirus / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; C516989:Birc5 protein, rat; C030659:K antigens; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3
keywords: Apoptotic-like death; Caspases; Cerebellar granule neurons; Cerebellum development; IAPs; Potassium deprivation