Ginsenoside Rd Protects Neurons Against Glutamate-Induced Excitotoxicity by Inhibiting Ca2+ Influx

被引:70
作者
Zhang, Chen [1 ]
Du, Fang [1 ]
Shi, Ming [1 ]
Ye, Ruidong [1 ]
Cheng, Haoran [1 ,2 ]
Han, Junliang [1 ]
Ma, Lei [1 ]
Cao, Rong [3 ]
Rao, Zhiren [3 ]
Zhao, Gang [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Neurol, Xian 710032, Peoples R China
[2] Lin Tong Air Force Aeromed Training Inst, Xian 710060, Peoples R China
[3] Fourth Mil Med Univ, Inst Neurosci, Xian 710032, Peoples R China
关键词
Ginsenoside Rd; Glutamate; Excitotoxicity; Calcium influx; NMDA receptor; NMDA RECEPTORS; ISCHEMIC-STROKE; NEUROTOXICITY; NOTOGINSENG; APOPTOSIS; CELLS;
D O I
10.1007/s10571-011-9742-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Our previous studies have demonstrated that ginsenoside Rd (GSRd), one of the principal ingredients of Pana notoginseng, has neuroprotective effects against ischemic stroke. However, the possible mechanism(s) underlying the neuroprotection of GSRd is/are still largely unknown. In this study, we treated glutamate-injured cultured rat hippocampal neurons with different concentrations of GSRd, and then examined the changes in neuronal apoptosis and intracellular free Ca2+ concentration. Our MTT assay showed that GSRd significantly increased the survival of neurons injured by glutamate in a dose-dependent manner. Consistently, TUNEL and Caspase-3 staining showed that GSRd attenuated glutamate-induced cell death. Furthermore, calcium imaging assay revealed that GSRd significantly attenuated the glutamate-induced increase of intracellular free Ca2+ and also inhibited NMDA-triggered Ca2+ influx. Thus, the present study demonstrates that GSRd protects the cultured hippocampal neurons against glutamate-induced excitotoxicity, and that this neuroprotective effect may result from the inhibitory effects of GSRd on Ca2+ influx.
引用
收藏
页码:121 / 128
页数:8
相关论文
共 39 条
[1]   GLUTAMATE-INDUCED NEURONAL DEATH - A SUCCESSION OF NECROSIS OR APOPTOSIS DEPENDING ON MITOCHONDRIAL-FUNCTION [J].
ANKARCRONA, M ;
DYPBUKT, JM ;
BONFOCO, E ;
ZHIVOTOVSKY, B ;
ORRENIUS, S ;
LIPTON, SA ;
NICOTERA, P .
NEURON, 1995, 15 (04) :961-973
[2]   Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats [J].
Cai, Bing-Xiang ;
Li, Xiao-Yan ;
Chen, Jing-Hui ;
Tang, Yong-Bo ;
Wang, Guan-Lei ;
Zhou, Jia-Guo ;
Qui, Qin-Ying ;
Guan, Yong-Yuan .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 606 (1-3) :142-149
[3]  
CHOI DW, 1990, ANNU REV NEUROSCI, V13, P171, DOI 10.1146/annurev.neuro.13.1.171
[4]   RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].
DENIZOT, F ;
LANG, R .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277
[5]  
Dingledine R, 1999, PHARMACOL REV, V51, P7
[6]   Pathobiology of ischaemic stroke: an integrated view [J].
Dirnagl, U ;
Iadecola, C ;
Moskowitz, MA .
TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397
[7]   Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor- and store-operated Ca2+ channels in vascular smooth muscle cells [J].
Guan, Yong-Yuan ;
Zhou, Jia-Guo ;
Zhang, Zheng ;
Wang, Guan-Lei ;
Cai, Bing-Xiang ;
Hong, Liang ;
Qiu, Qin-Ying ;
He, Hua .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 548 (1-3) :129-136
[8]   Culturing hippocampal neurons [J].
Kaech, Stefanie ;
Banker, Gary .
NATURE PROTOCOLS, 2006, 1 (05) :2406-2415
[9]   NMDA receptors in clinical neurology: excitatory times ahead [J].
Kalia, Lorraine V. ;
Kalia, Suneil K. ;
Salter, Michael W. .
LANCET NEUROLOGY, 2008, 7 (08) :742-755
[10]   Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons [J].
Kim, S ;
Kim, T ;
Ahn, K ;
Park, WK ;
Nah, SY ;
Rhim, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 323 (02) :416-424