Document Detail


Knockdown of glycogen synthase kinase 3 beta attenuates 6-hydroxydopamine-induced apoptosis in SH-SY5Y cells.
MedLine Citation:
PMID:  20920551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yi Li; Feifei Luo; Lei Wei; Zhuolin Liu; Pingyi Xu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-22
Journal Detail:
Title:  Neuroscience letters     Volume:  487     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-03-09     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  41-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
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MeSH Terms
Descriptor/Qualifier:
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 / diagnostic use
Thiazoles / diagnostic use
Time Factors
Chemical
Reg. No./Substance:
0/Adrenergic Agents; 0/RNA, Small Interfering; 0/Tetrazolium Salts; 0/Thiazoles; 1199-18-4/Oxidopamine; 298-93-1/thiazolyl blue; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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