Neuroprotective effect of paeoniflorin on okadaic acid-induced tau hyperphosphorylation via calpain/Akt/GSK-3β pathway in SH-SY5Y cells
Neuroprotective effect of paeoniflorin on okadaic acid-induced tau hyperphosphorylation via calpain/Akt/GSK-3β pathway in SH-SY5Y cells
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芍药苷对 SH-SY5Y 细胞中大田酸通过钙蛋白酶/Akt/GSK-3 beta 途径诱导的 tau 蛋白过度磷酸化的神经保护作用
DOI：
10.1016/j.brainres.2018.03.022
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发表时间：
2018-07-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Qi
中科院分区：
文献类型：
--
作者：
Ma, Xiao-Hui;Duan, Wen-Jun;Wang, Qi
tau蛋白的异常磷酸化是痴呆最常见的症状之一，在阿尔茨海默病的病因学和发展研究中变得越来越重要。芍药苷是芍药的主要生物活性成分，是一种单萜苷，据报道对神经退行性疾病具有有益作用。然而，芍药苷对tau蛋白病的作用仍然不明确。用冈田酸（OA）处理SH-SY 5 Y细胞8小时以诱导tau磷酸化，未观察到细胞死亡。光学显微镜结果显示，芍药苷改善冈田酸诱导的细胞形态学变化，包括细胞肿胀和突触缩短。Western blotting数据表明芍药苷逆转冈田酸诱导的tau过度磷酸化，其通过抑制钙蛋白酶、Akt和GSK-3 β的活性而增强。透射电镜结果表明，芍药苷单独作用可减少自噬体的数量，稳定微管结构。此外，钙蛋白酶抑制剂和芍药苷增强芍药苷对稳定微管的作用。此外，钙蛋白酶抑制剂显着增强芍药苷逆转冈田酸降低的MAP-2和β III-微管蛋白（两种微管相关蛋白）荧光强度的作用。本研究表明芍药苷通过干扰钙蛋白酶/Akt/GSK-3 β相关通路保护SH-SY 5 Y细胞免受冈田酸攻击，其中可能涉及自噬。此外，芍药苷还能减轻冈田酸对微管结构系统的应激反应。本研究中呈现的结果表明，芍药苷可能在tau蛋白病中起重要作用。(C)2018 Elsevier B. V.版权所有。
Abnormal phosphorylation of tau, one of the most common symptoms of dementia, has become increasingly important in the study of the etiology and development of Alzheimer's disease. Paeoniflorin, the main bioactive component of herbaceous peony, is a monoterpene glycoside, which has been reported to exert beneficial effects on neurodegenerative disease. However, the effect of paeoniflorin on tauopathies remains ambiguous. SH-SY5Y cells were treated with okadaic acid (OA) for 8 h to induce tau phosphorylation and no cell death was observed. Optical microscopy results showed that paeoniflorin ameliorated okadaic acid induced morphological changes, including cell swelling and synapsis shortening. Western blotting data illustrated that paeoniflorin reversed okadaic acid induced tau hyperphosphorylation, which was enhanced by inhibiting the activities of calpain, Akt and GSK-3 beta. Transmission electron microscopy results showed that paeoniflorin alone can reduce the number of autophagosomes and stabilize the microtubule structure. In addition, calpastain and paeoniflorin enhance the effect of paeoniflorin on stabilizing microtubules. In addition, calpastain markedly enhanced the effect of paeoniflorin on reversing okadaic acid-lowered fluorescence intensity of both MAP-2 and beta III-tubulin, two microtubule-associated proteins. This study shows that paeoniflorin protected SH-SY5Y cells against okadaic acid assault by interfering with the calpain/Akt/GSK-3 beta-related pathways, in which autophagy might be involved. Besides, paeoniflorin is found to relieve the stress response of the microtubule structure system caused by okadaic acid treatment. The results presented in this study suggest that paeoniflorin potentially plays an important role in tauopathies. (C) 2018 Elsevier B.V. All rights reserved.