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.
Highlights
Ischemic stroke due to lack of cerebral blood supply is one of the most common causes leading to death or disability in adults worldwide [1]
To investigate the protection of Ginsenoside Rb1 (GRb1) against neuronal death, we compared cellular viability at recovery 24 h between the groups treated with oxygen glucose deprivation (OGD) and treated with
We found that the increment of acridine orange-positive acidic vesicular organelles (AVO) in the OGD group was inhibited by administration of GRb1 prior to OGD
Summary
Ischemic stroke due to lack of cerebral blood supply is one of the most common causes leading to death or disability in adults worldwide [1]. Transient global brain ischemia arising during cardiac arrest, cardiac surgery or induced experimentally in animals via bilateral carotid artery occlusion, causes highly selective, delayed neuronal death [2] Multiple factors such as oxidative stress, endoplasmic reticulum stress, and calcium overload have been identified to participate in the process of ischemic neuronal death [3], autophagy is found to play an important role in regulating neuronal death induced by trauma and hypoxia [4,5], and by ischemia/reperfusion [6]. We used in vitro and in vivo experimental models of cerebral ischemic injury to investigate the role of the PI3k/Akt pathway in the protection of GRb1 against lethal autophagy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
