Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

Jun Xu,Kaifeng Zhou,Zhongyue Huang,Xiaofan Yin,Liang Wu,Huijie Gu,Yiming Zhang

doi:10.18632/oncotarget.22055

Abstract

The present study tested the potential effect of OSU53, a novel AMPK activator, against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal cord neurons. OSU53 activated AMPK signaling, which is required for its actions in spinal cord neurons. The AMPK inhibitor Compound C or AMPKα1 siRNA almost abolished OSU53-mediated neuroprotection against H2O2. On the other hand, sustained-activation of AMPK by introducing the constitutive-active AMPKα1 mimicked OSU53's actions, and protected spinal cord neurons from oxidative stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species production, lipid peroxidation and DNA damages in spinal cord neurons. Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression in H2O2-treated spinal cord neurons. Together, we indicate that targeted-activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

Highlights

Oxidative stress following the spinal cord injury is a main cause of secondary damages to neurons [1,2,3]
To mimic oxidative stress in vitro, primary cultured murine spinal cord neurons were treated with hydrogen peroxide (H2O2) at different concentrations, from 50
Cell Counting Kit-8 (CCK-8) assay results in Figure 1A demonstrated that H2O2 dose-dependently inhibited survival of the murine spinal cord neurons

Summary

Introduction

Oxidative stress following the spinal cord injury is a main cause of secondary damages to neurons [1,2,3]. AMPK (AMP-activated protein kinase) is a key regulator of cellular energy [5, 6]. AMPK activates/inactivates its downstream effectors to promote cell survival under stress conditions [7,8,9,10,11]. Activated AMPK protects cells from oxidative stress by increasing NADPH (nicotinamide adenine dinucleotide phosphate) content [7,8,9]. AMPK-activated cell autophagy could be pro-survival [8, 10, 11]

Methods

Results

Conclusion