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Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity
被引:47
|作者:
Sun, Fang-ling
[1
]
Zhang, Lan
[1
]
Zhang, Ru-yi
[1
]
Li, Lin
[1
]
机构:
[1] Capital Med Univ, Xuanwu Hosp, Dept Pharmacol, Key Lab Neurodegenerat Dis,Minist Educ, Beijing 100053, Peoples R China
基金:
中国国家自然科学基金;
北京市自然科学基金;
关键词:
Tetrahydroxystilbene glucoside;
MPP+;
Mitochondrion;
Oxidative stress;
Apoptosis;
Parkinson's disease;
PARKINSONS-DISEASE;
INDUCED APOPTOSIS;
DOPAMINERGIC-NEURONS;
ATTENUATES MPP+;
ALPHA-SYNUCLEIN;
CYTOCHROME-C;
PC12;
CELLS;
DEATH;
MITOCHONDRIA;
EXPRESSION;
D O I:
10.1016/j.ejphar.2011.03.046
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
1-Methyl-4-phenylpyridinium (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin for inducing a cell model of Parkinson's disease. This study aimed to evaluate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on MPP+-induced cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. The results from the KIT and lactate dehydrogenase (LDH) assays showed that incubating cells with 500 mu M MPP+ for 24 h decreased cell viability and increased LDH leakage, whereas preincubating cells with 3.125 to 50 mu M TSG for 24 h protected the cells against MPP+-induced cell damage. Using 2',7'-dichlorofluorescin diacetate (DCFH-DA) and rhodamine 123, respectively, we found that TSG inhibited both the elevation of intracellular reactive oxygen species and the disruption of mitochondrial membrane potential induced by MPP+. In addition, TSG suppressed both the upregulation of the ratio of Bax to Bcl-2 and the activation of caspase-3 induced by MPP+, and TSG inhibited apoptosis as detected by flow cytometric analysis using Annexin-V and propidium (PI) label. These results suggest that TSG may protect neurons against MPP+-induced cell death through improving mitochondrial function, decreasing oxidative stress and inhibiting apoptosis, and this may provide a potentially new strategy for preventing and treating neurodegenerative disorders such as Parkinson's disease. (C) 2011 Elsevier B.V. All rights reserved.
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页码:283 / 290
页数:8
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