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
北京市自然科学基金; 中国国家自然科学基金;
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.
引用
收藏
页码:283 / 290
页数:8
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