Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca2+ Influx

被引:26
作者
Wang, Ke [1 ]
Zhu, Xue [1 ]
Zhang, Kai [1 ]
Wu, Zhifeng [2 ]
Sun, Song [2 ]
Zhou, Fanfan [3 ]
Zhu, Ling [4 ]
机构
[1] Jiangsu Inst Nucl Med, Minist Hlth, Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Wuxi 214063, Peoples R China
[2] Nanjing Med Univ, Wuxi Peoples Hosp 2, Dept Ophthalmol, Wuxi 214002, Peoples R China
[3] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia
[4] Univ Sydney, Save Sight Inst, Sydney, NSW 2000, Australia
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2016年 / 17卷 / 07期
基金
中国国家自然科学基金;
关键词
glutamate toxicity; retinal degenerative diseases; Y-79; cells; puerarin; PHOTORECEPTOR DEGENERATION; MACULAR DEGENERATION; ACTIVATION; APOPTOSIS; TOXICITY; NEUROTOXICITY; PHARMACOLOGY; MECHANISM; NEURONS; PROTEIN;
D O I
10.3390/ijms17071109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glutamate toxicity is estimated to be the key cause of photoreceptor degeneration in the pathogenesis of retinal degenerative diseases. Oxidative stress and Ca2+ influx induced by glutamate are responsible for the apoptosis process of photoreceptor degeneration. Puerarin, a primary component of Kudzu root, has been widely used in the clinical treatment of retinal degenerative diseases in China for decades; however, the detailed molecular mechanism underlying this effect remains unclear. In this study, the neuroprotective effect of puerarin against glutamate-induced cytotoxicity in the differentiated Y-79 cells was first investigated through cytotoxicity assay. Then the molecular mechanism of this effect regarding anti-oxidative stress and Ca2+ hemostasis was further explored with indirect immunofluorescence, flow cytometric analysis and western blot analysis. Our study showed that glutamate induced cell viability loss, excessive reactive oxygen species (ROS) generation, calcium overload and up-regulated cell apoptosis in differentiated Y-79 cells, which effect was significantly attenuated with the pre-treatment of puerarin in a dose-dependent manner. Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial-dependent signaling pathway and calmodulin-dependent protein kinase II (CaMKII)-dependent apoptosis signal-regulating kinase 1(ASK-1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases.
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页数:13
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