Document Detail

Synaptophysin enhances the neuroprotection of VMAT2 in MPP+-induced toxicity in MN9D cells.
MedLine Citation:
PMID:  16023584     Owner:  NLM     Status:  MEDLINE    
The use of the potent neurotoxin MPTP in producing a model for Parkinson's disease (PD) has allowed us to dissect the cellular processes responsible for both selective neuronal vulnerability and neuroprotection in idiopathic PD. It has been suggested that vesicular monoamine transporters (VMATs) play a critical neuroprotective role in MPP+ toxicity. However, little is known about how this detoxificative sequestration in dopaminergic (DAergic) neurons is regulated at the molecular and cellular levels. Using the DAergic cell line MN9D as an in vitro model, we found that overexpression of VMAT2 (a neuronal isoform of VMATs) protects the transformants from MPP+-induced toxicity, consistent with the previous work on fibroblastic CHO cells. We further found that the MN9D cells displayed lower expression levels of secretory vesicle proteins such as synaptophysin. Overexpression of synaptophysin in MN9D cells can significantly increase the resistance of the transformants to MPP+ toxicity. The co-expression of VMAT2 and synaptophysin has shown synergistic protection for the transformants, suggesting a role of synaptophysin in the biogenesis of secretory vesicles and in influencing the targeting of VMAT2 to these vesicles. Our work indicates that both the expression level of VMAT2 and capacity of vesicular packaging of DA are important in protecting DAergic cells from MPP+ toxicity.
Carol X-Q Chen; Steven Y Huang; Limei Zhang; Yong-Jian Liu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurobiology of disease     Volume:  19     ISSN:  0969-9961     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-18     Completed Date:  2005-08-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-26     Citation Subset:  IM    
Department of Neurology, University of Pittsburgh School of Medicine, W958 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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MeSH Terms
1-Methyl-4-phenylpyridinium / toxicity*
Blotting, Western
CHO Cells
Dopamine / metabolism
Membrane Glycoproteins / metabolism*
Membrane Transport Proteins / metabolism*
Neurons / drug effects*,  metabolism
Neurotoxins / toxicity*
PC12 Cells
Secretory Vesicles / drug effects,  metabolism
Synaptophysin / metabolism*
Vesicular Biogenic Amine Transport Proteins
Vesicular Monoamine Transport Proteins
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Neurotoxins; 0/SLC18A2 protein, human; 0/Slc18a2 protein, rat; 0/Synaptophysin; 0/Vesicular Biogenic Amine Transport Proteins; 0/Vesicular Monoamine Transport Proteins; 48134-75-4/1-Methyl-4-phenylpyridinium

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