Protective Effects of Gastrodin Against Autophagy-Mediated Astrocyte Death

被引:48
|
作者
Wang, Xin-shang [1 ]
Tian, Zhen [1 ]
Zhang, Nan [1 ]
Han, Jing [1 ]
Guo, Hong-liang [1 ]
Zhao, Ming-gao [1 ]
Liu, Shui-bing [1 ]
机构
[1] Fourth Mil Med Univ, Sch Pharm, Dept Pharmacol, Xian 710032, Peoples R China
基金
中国国家自然科学基金;
关键词
gastrodin; autophagy; astrocyte; lipopolysaccharides; GLUTAMINE-SYNTHETASE; HIPPOCAMPAL-NEURONS; PRIMARY CULTURES; INFLAMMATION; NEURODEGENERATION; EXCITOTOXICITY; NEUROTOXICITY; INVOLVEMENT; P62/SQSTM1; METABOLISM;
D O I
10.1002/ptr.5538
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Gastrodin is an active ingredient derived from the rhizome of Gastrodia elata. This compound is usually used to treat convulsive illness, dizziness, vertigo, and headache. This study aimed to investigate the effect of gastrodin on the autophagy of glial cells exposed to lipopolysaccharides (LPS, 1 mu g/mL). Autophagy is a form of programmed cell death, although it also promotes cell survival. In cultured astrocytes, LPS exposure induced excessive autophagy and apoptosis, which were significantly prevented by the pretreatment cells with gastrodin (10M). The protective effects of gastrodin via autophagy inhibition were verified by the decreased levels of LC3-II, P62, and Beclin-1, which are classical markers for autophagy. Furthermore, gastrodin protected astrocytes from apoptosis through Bcl-2 and Bax signaling pathway. The treatment of astrocytes with rapamycin (500nM), wortmannin (100nM), and LY294002 (10M), which are inhibitors of mTOR and PI3K, respectively, eliminated the known effects of gastrodin on the inhibited Beclin-1 expression. Furthermore, gastrodin blocked the down-regulation of glutamine synthetase induced by LPS exposure in astrocytes. Our results suggest that gastrodin can be used as a preventive agent for the excessive autophagy induced by LPS. Copyright (c) 2015 John Wiley & Sons, Ltd.
引用
收藏
页码:386 / 396
页数:11
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