Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults.
Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults.
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通过激活 PI3K/Akt 通路抑制自噬有助于保护人参皂苷 Rb1 免受缺血性损伤引起的神经元死亡
DOI：
10.3390/ijms150915426
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发表时间：
2014-09-01
影响因子：
5.6
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Luo T;Liu G;Ma H;Lu B;Xu H;Wang Y;Wu J;Ge P;Liang J
致死性自噬是短暂性全脑缺血导致神经元死亡的一条途径。在这项研究中，我们研究了人参皂苷Rb 1（Ginsenoside Rb 1，GRb 1）对缺血/再灌注诱导的自噬性神经元死亡的影响，并研究了PI 3 K/Akt的作用。采用氧糖剥夺（OGD）诱导SH-SY 5 Y细胞缺血性神经元死亡，采用双血管阻断法造成大鼠短暂性全脑缺血。MTT法检测SH-SY 5 Y细胞存活率，苏木精-伊红染色检测海马CA 1区神经元死亡情况。采用荧光显微镜结合吖啶橙子（AO）和单丹酰尸胺（MDC）染色和透射电镜观察自噬泡。Western blotting分析LC 3 II、Beclin 1、总Akt和Ser 473磷酸化Akt蛋白水平。GRb 1抑制OGD和短暂缺血诱导的神经元死亡，减轻OGD诱导的自噬空泡在SH-SY 5 Y细胞。相反，PI 3 K抑制剂LY 294002抵消了GRb 1对OGD或短暂缺血引起的神经元死亡的保护作用。LY 294002不仅可以减轻GRb 1引起的Akt蛋白水平上调，而且可以逆转GRb 1对OGD和短暂性脑缺血引起的LC 3 II和Beclin 1蛋白水平升高的抑制作用。
Lethal autophagy is a pathway leading to neuronal death caused by transient global ischemia. In this study, we examined the effect of Ginsenoside Rb1 (GRb1) on ischemia/reperfusion-induced autophagic neuronal death and investigated the role of PI3K/Akt. Ischemic neuronal death in vitro was induced by using oxygen glucose deprivation (OGD) in SH-SY5Y cells, and transient global ischemia was produced by using two vessels occlusion in rats. Cellular viability of SH-SY5Y cells was assessed by MTT assay, and CA1 neuronal death was evaluated by Hematoxylin-eosin staining. Autophagic vacuoles were detected by using both fluorescent microscopy in combination with acridine orange (AO) and Monodansylcadaverine (MDC) staining and transmission electronic microscopy. Protein levels of LC3II, Beclin1, total Akt and phosphor-Akt at Ser473 were examined by western blotting analysis. GRb1 inhibited both OGD and transient ischemia-induced neuronal death and mitigated OGD-induced autophagic vacuoles in SH-SY5Y cells. By contrast, PI3K inhibitor LY294002 counteracted the protection of GRb1 against neuronal death caused by either OGD or transient ischemia. LY294002 not only mitigated the up-regulated protein level of phosphor Akt at Ser473 caused by GRb1, but also reversed the inhibitory effect of GRb1 on OGD and transient ischemia-induced elevation in protein levels of LC3II and Beclin1.
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影响因子：
6.1
作者：
Janelidze, S;Hu, BR;Siesjö, BK
通讯作者：
Siesjö, BK
影响因子：
9.3
作者：
Hou X;Hu Z;Xu H;Xu J;Zhang S;Zhong Y;He X;Wang N
通讯作者：
Wang N
影响因子：
8.2
作者：
Mo, Zhen-tao;Fang, Yong-qi;Zhang, Sheng
通讯作者：
Zhang, Sheng
影响因子：
3.3
作者：
Lu, Jian;Qian, Hui-Yin;Zhu, Chang-Lai
通讯作者：
Zhu, Chang-Lai
人参皂苷 Rb1 对谷氨酸诱导的神经毒性的神经保护作用：重点是自噬
影响因子：
2.5
作者：
Chen, Zhaoyao;Lu, Tingting;Xu, Gelin
通讯作者：
Xu, Gelin