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

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

doi:10.18632/oncotarget.22055

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Research Papers:

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

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

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Oncotarget. 2017; 8:112477-112486. https://doi.org/10.18632/oncotarget.22055

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Abstract

Jun Xu1, Liang Wu1,*, Yiming Zhang1, Huijie Gu1, Zhongyue Huang1, Kaifeng Zhou1 and Xiaofan Yin1

1Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, China

*Co-First author

Correspondence to:

Xiaofan Yin, email: [email protected]

Keywords: spinal cord injury, oxidative stress, AMPK and OSU53

Received: July 27, 2017 Accepted: August 28, 2017 Published: October 23, 2017

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.

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Research Papers:

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

Abstract