Format

Send to

Choose Destination
Int J Mol Sci. 2014 Sep 1;15(9):15426-42. doi: 10.3390/ijms150915426.

Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults.

Author information

1
Department of Neurology, First Hospital of Jilin University, Changchun 130021, China. luotianfei2010@126.com.
2
Department of Pediatrics, Anzhen Hospital of Capital University of Medical Sciences, Beijing 10029, China. liugvying@126.com.
3
Department of Pathology, First Hospital of Jilin University, Changchun 130021, China. mahongxi1969@163.com.
4
Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China. Lubin03216@163.com.
5
Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China. xuhaiyang76@163.com.
6
Department of Pediatrics, First Hospital of Jilin University, Changchun 130021, China. yujingwang2012@126.com.
7
Department of Neurology, First Hospital of Jilin University, Changchun 130021, China. drwujiang2010@163.com.
8
Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China. pengfeige@gmail.com.
9
Department of Pediatrics, First Hospital of Jilin University, Changchun 130021, China. jakcyliangjm@163.com.

Abstract

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.

PMID:
25257523
PMCID:
PMC4200757
DOI:
10.3390/ijms150915426
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center