Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 against Neuronal Death Caused by Ischemic Insults

被引：117

作者：

Luo, Tianfei ^{[1
]}

Liu, Guiying ^{[2
]}

Ma, Hongxi ^{[3
]}

Lu, Bin ^{[4
]}

Xu, Haiyang ^{[4
]}

Wang, Yujing ^{[5
]}

Wu, Jiang ^{[1
]}

Ge, Pengfei ^{[4
]}

Liang, Jianmin ^{[5
]}

机构：

[1] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Peoples R China

[2] Capital Univ Med Sci, Anzhen Hosp, Dept Pediat, Beijing 10029, Peoples R China

[3] Jilin Univ, Hosp 1, Dept Pathol, Changchun 130021, Peoples R China

[4] Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130021, Peoples R China

[5] Jilin Univ, Hosp 1, Dept Pediat, Changchun 130021, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2014年 / 15卷 / 09期

关键词：

autophagy; OGD; transient global ischemia; Ginsenoside Rb1; PI3K/Akt; TRANSIENT CEREBRAL-ISCHEMIA; CELL-DEATH; INDUCED APOPTOSIS; CYTOCHROME-C; BRAIN; INJURY; AKT; NEUROGENESIS; REPERFUSION; CANCER;

D O I：

10.3390/ijms150915426

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：15426 / 15442

页数：17

共 43 条

[1]

Ginsenoside Rb1 Suppresses Ultraviolet Radiation-Induced Apoptosis by Inducing DNA Repair [J].