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

Abstract
Glycogen synthase kinase 3 beta (GSK3β) plays a critical role in signal transductions concerning neuronal death. In the present study, we investigated the potential role of GSK3β in 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma cell line SH-SY5Y. We assessed the apoptotic proteins and the relative levels of pGSK3β (Ser9) and pGSK3β (Tyr216) to GSK3β in 6-OHDA-treated SH-SY5Y. Furthermore, we downregulated the expression of GSK3β 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-OHDA increased the expression of caspase-3 and caspase-9 but not caspase-8. Additionally, 6-OHDA decreased the ratio of pGSK3β (Ser9)/GSK3β and increased the ratio of pGSK3β (Tyr216)/GSK3β. Moreover, 6-OHDA induced less cell viability loss and lower expression of caspase-9 and caspase-3 in GSK3β knockdown group compared with control. The present data indicate that 6-OHDA may induce apoptosis in SH-SY5Y via the intrinsic death pathway and GSK3β knockdown can partly attenuate 6-OHDA-induced neuronal death and apoptosis, suggesting that GSK3β may have the potential to serve as a therapeutic target for PD.
AuthorsYi Li, Feifei Luo, Lei Wei, Zhuolin Liu, Pingyi Xu
JournalNeuroscience letters (Neurosci Lett) Vol. 487 Issue 1 Pg. 41-6 (Jan 3 2011) ISSN: 1872-7972 [Electronic] Ireland
PMID20920551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Adrenergic Agents
  • RNA, Small Interfering
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • Oxidopamine
  • glycogen synthase kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Caspases
Topics
  • Adrenergic Agents (toxicity)
  • Analysis of Variance
  • Apoptosis (drug effects)
  • Caspases (metabolism)
  • Cell Count (methods)
  • Cell Line, Tumor
  • Glycogen Synthase Kinase 3 (deficiency, genetics)
  • Humans
  • Neuroblastoma (pathology)
  • Oxidopamine (toxicity)
  • RNA, Small Interfering (pharmacology)
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors

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