Role of inhibitor of apoptosis proteins and Smac/DIABLO in staurosporine-induced cerebellar granule neurons death.
Apoptosis is characterized by morphological and biochemical alterations mediated by caspases. The Inhibitor of Apoptosis Proteins (IAP) comprises a family of proteins that regulate apoptosis by inhibiting caspases. IAP are controlled by different mechanisms including transcriptional regulation, ubiquitination and interaction with proapoptotic proteins such as Smac/DIABLO. Here, we evaluated the role of IAP and Smac/DIABLO in neuronal death. We used cultured rat cerebellar granule neurons (CGN) under conditions that induce apoptosis (staurosporine). We found the expression of cIAP-1, cIAP-2, XIAP and survivin, but not BRUCE in CGN under survival conditions. When CGN were treated with staurosporine we detected a decrease in cIAP-1 and cIAP-2, but not in XIAP and survivin levels. Under these conditions Smac/DIABLO was released from the mitochondria suggesting its involvement in staurosporine-induced death of CGN. However, the Smac N7 peptide, which interacts with caspase-9 binding site in XIAP, did not show any effect on CGC viability.
Maycotte
P
P
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo Postal 70-253, 04510, Mexico, DF, Mexico.
Blancas
S
S
Morán
J
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology*; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C516989:Birc5 protein, rat; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D010455:Peptides; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; D019311:Staurosporine