Protective Effects of Gastrodin Against Autophagy‐Mediated Astrocyte Death
Protective Effects of Gastrodin Against Autophagy‐Mediated Astrocyte Death
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DOI：
10.1002/ptr.5538
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发表时间：
2016-03
影响因子：
7.2
通讯作者：
Xin-shang Wang;Zhen Tian;Nan Zhang;Jing Han;Hong-liang Guo;Ming-gao Zhao;Shui-bing Liu
中科院分区：
文献类型：
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作者：
Xin-shang Wang;Zhen Tian;Nan Zhang;Jing Han;Hong-liang Guo;Ming-gao Zhao;Shui-bing Liu
天麻素是从天麻根茎中提取的有效成分。这种化合物通常用于治疗抽搐、头晕、眩晕和头痛。本研究旨在探讨天麻素对脂多糖(1µg/mL)诱导的神经胶质细胞自噬的影响。自噬是细胞程序性死亡的一种形式，尽管它也能促进细胞存活。在培养的星形胶质细胞中，脂多糖可诱导过度的自噬和细胞凋亡，天麻素(10μM)可显著抑制这种作用。天麻素通过抑制自噬发挥保护作用，通过降低自噬的经典标志物Lc3-II、p62和Beclin-1的水平来验证。此外，天麻素还通过Bcl2和Bax信号通路保护星形胶质细胞免于凋亡。分别用mTOR和PI3K的抑制剂雷帕霉素(500 NM)、Wortmannin(100 NM)和LY294002(10μM)处理星形胶质细胞，可消除天麻素对抑制Beclin-1表达的已知作用。此外，天麻素可阻断脂多糖诱导的星形胶质细胞谷氨酰胺合成酶的下调。我们的结果表明，天麻素可以作为一种预防脂多糖诱导的过度自噬的药物。版权所有©2015 John Wiley&Sons，Ltd.
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 µg/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 (10 μM). 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 (500 nM), wortmannin (100 nM), and LY294002 (10 μM), 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 © 2015 John Wiley & Sons, Ltd.