Document Detail


Caspase-2 and caspase-8 trigger caspase-3 activation following 6-OHDA-induced stress in human dopaminergic neurons differentiated from ReNVM stem cells.
MedLine Citation:
PMID:  23540413     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of the study was to establish a suitable model to study Parkinson's disease (PD) pathogenesis in differentiated dopaminergic neurons (dDCN). The specific aim was to demonstrate the involvement of the caspase family and to identify specific caspases which are activated by 6-hydroxydopamine (6OHD) treatment leading to death of dDCN.
METHODS: ReNcell VM cells were differentiated into dDCN and were exposed to 6OHD to induce stress. Western blot (WB) and double immunofluorescent analyses of caspases-2, -3, and -8 were carried out in untreated and 6OHD-treated dDCN. zVADfmk was used to determine if it could inhibit activation of caspases-2, -3, and -8 in dDCN following 6OHD-mediated stress.
RESULTS: Our immunofluorescent and WB data showed that 6OHD triggered caspases-2 and -8 activation which in turn activated caspase-3 leading to death of dDCN. Additionally, WB analysis revealed that caspases-2, -3, and -8 activation was reduced by zVADfmk in 6OHD-treated cells.
DISCUSSION: The study showed that 6OHD-induced toxicity triggered caspase mediated death of dDCN. This finding is in support of previous studies using different PD model showing that 6OHD can induce caspases-2 and -3 activation through apoptotic pathway and that both caspases can activate caspase-3 in PD. In addition, our results suggest that caspase-2 cause's cell death might be via an indirect NF kappaB route. This study has established a PD model which can provide better insight to PD pathogenesis on a biochemical and molecular level, leading to a better understanding of PD and potential for new treatments.
Authors:
Zohara L Chaudhry; Bushra Y Ahmed
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurological research     Volume:  35     ISSN:  1743-1328     ISO Abbreviation:  Neurol. Res.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905298     Medline TA:  Neurol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  435-40     Citation Subset:  IM    
Affiliation:
Park Square, University of Bedfordshire, UK.
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