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

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 requir...

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Detalles Bibliográficos
Autores principales: Xu, Jun, Wu, Liang, Zhang, Yiming, Gu, Huijie, Huang, Zhongyue, Zhou, Kaifeng, Yin, Xiaofan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762526/
https://www.ncbi.nlm.nih.gov/pubmed/29348841
http://dx.doi.org/10.18632/oncotarget.22055
Descripción
Sumario: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.