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Cell Stress and Chaperones

, Volume 24, Issue 6, pp 1091–1099 | Cite as

Protodioscin protects PC12 cells against oxygen and glucose deprivation-induced injury through miR-124/AKT/Nrf2 pathway

  • Kun Shu
  • Yuelin ZhangEmail author
Original Paper

Abstract

The purpose of the current study was to demonstrate the neuroprotective effect of protodioscin (Prot) in an in vitro model of ischemia/reperfusion (I/R) and investigate the underlying molecular mechanism. After PC12 cells were exposed to oxygen and glucose deprivation (OGD) reperfusion, PI staining by flow cytometry was used to quantify the rate of apoptosis. The levels of hypoxia-inducible factor 1-alpha (HIF-1α), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were determined using commercially available kits. Intracellular reactive oxygen species (ROS) level was detected using the 20,70-dichlorodihy-drofluorescein diacetate (DCFH-DA) fluorescence assay. The expression levels of heat-shock proteins (HSP), PI3K, AKT, Nrf2, and miR-124 were tested by western blot or quantitative PCR. Prot significantly attenuated oxygen–glucose deprivation/reperfusion (OGD/R)-induced apoptotic death. Prot also reduced the oxidative stress as revealed by increasing the activities of SOD and GSH-Px, decreasing the levels of ROS and MDA. Moreover, mechanism investigations suggested that Prot prevented the decrease of HSP70, HSP32 (hemeoxygenase-1, HO-1), and PI3K protein expression, phosphorylation of AKT, and the accumulation of nuclear Nrf2. The level of miR-124 was decreased in PC12 cells, which was also effectively reversed by Prot treatment. Prot protected PC12 cells against OGD/R-induced injury through inhibiting oxidative stress and apoptosis, which could be associated with increasing HSP proteins expression via activating PI3K/AKT/Nrf2 pathway and miR-124 modulation.

Keywords

Protodioscin Antioxidant OGD/R Heat-shock protein miR-124 PI3K/AKT Nrf2 

Abbreviations

Prot

Protodioscin

OGD/R

Oxygen–glucose deprivation/reperfusion

HIF-1α

Hypoxia-inducible factor 1-alpha

SOD

Superoxide dismutase

GSH-Px

Glutathione peroxidase

MDA

Malondialdehyde

ROS

Reactive oxygen species

HSP

Heat shock proteins

HO-1

Hemeoxygenase-1

Nrf2

Nuclear factor (erythroid-derived 2)-like 2

PI3K

Phosphatidylinositol-3 kinase

Notes

Funding information

This work is supported by the Xi’an Jiaotong University, Xi’an, Shanxi, China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  1. 1.Department of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of NeurosurgeryThe Third Affiliated Hospital of Xi’an Jiaotong UniversityXi’an CityChina

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