Role of inhibitor of apoptosis proteins and Smac/DIABLO in staurosporine-induced cerebellar granule neurons death

Abstract

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.