A novel WD-40 repeat protein WDR26 suppresses H 2O 2-induced cell death in neural cells

Abstract

WD-40 repeat proteins play important roles in a variety of cellular functions, such as cell growth, proliferation, apoptosis and intracellular signal transduction. We previously identified a novel member of this family, WDR26. To examine the biological function of WDR26, we used hWDR26 plasmids and antisense phosphorothioate oligodeoxynucleotides (asODNs) against WDR26 to examine its role in response to oxidative stress in human SH-SY5Y neuroblastoma cells. Our results showed that H 2O 2 at 0.5 mM substantially induced cell death and significantly up-regulated the WDR26 expression, and WDR26 over-expression in turn strongly suppressed H 2O 2-induced cell death. Moreover, asODNs markedly inhibited the de novo biosynthesis of WDR26, which contributed to enhanced cell death induced by H 2O 2. Finally, we found that WDR26 over-expression also down-regulated the transcriptional activity of AP-1 during H 2O 2-induced SH-SY5Y cell death. Taken together, these results indicated that WDR26 was up-regulated by oxidative stress and played a key role in H 2O 2-induced SH-SY5Y cell death, which may be mediated by the down-regulation of AP-1 transcriptional activity.