Synaptophysin enhances the neuroprotection of VMAT2 in MPP+-induced toxicity in MN9D cells

被引:37
作者
Chen, CXQ
Huang, SY
Zhang, LM
Liu, YJ
机构
[1] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA
基金
美国国家卫生研究院;
关键词
Parkinson's disease; neuroprotection; MPP+ toxicity; MN9D; VMAT2; synaptophysin;
D O I
10.1016/j.nbd.2005.01.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 monnamine 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 MPPO+ toxicity. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:419 / 426
页数:8
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