Knockdown of glycogen synthase kinase 3 beta attenuates 6-hydroxydopamine-induced apoptosis in SH-SY5Y cells

Glycogen synthase kinase 3 beta (GSK3 beta) plays a critical role in signal transductions concerning neuronal death. In the present study, we investigated the potential role of GSK3 beta in 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma cell line SH-SY5Y. We assessed the apoptotic proteins and the relative levels of pGSK3 beta (Ser9) and pGSK3 beta (Tyr216) to GSK3 beta in 6-OHDA-treated SH-SY5Y. Furthermore, we downregulated the expression of GSK3 beta by short hairpin RNA (shRNA) interference and compared the cell viability and expression of apoptotic proteins in knockdown group with those in control group under the treatment of 6-OHDA. We found that 6-0HDA increased the expression of caspase-3 and caspase-9 but not caspase-8. Additionally, 6-0HDA decreased the ratio of pGSK3 beta (Ser9)/GSK3 beta and increased the ratio of pGSK3 beta (Tyr216)/GSK3 beta. Moreover, 6-0HDA induced less cell viability loss and lower expression of caspase-9 and caspase-3 in GSK3 beta knockdown group compared with control. The present data indicate that 6-0HDA may induce apoptosis in SH-SY5Y via the intrinsic death pathway and GSK3 beta knockdown can partly attenuate 6-OHDA-induced neuronal death and apoptosis, suggesting that GSK3 beta may have the potential to serve as a therapeutic target for PD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.