SC79 protects dopaminergic neurons from oxidative stress
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Yan Xu1, Ya-Wen Gao1 and Yu Yang1
1Geriatrics Department, The Second Xiang Ya Hospital of Central South University, Changsha, China
Keywords: SC79; Akt; dopaminergic neurons; oxidative stress
Received: November 02, 2017 Accepted: December 01, 2017 Published: December 20, 2017
Oxidative stress could lead to dopaminergic neuronal cell death. SC79 is a novel, selective and highly-efficient Akt activator. The current study tested its effect in dopaminergic neurons with oxidative stress. In both SH-SY5Y cells and primary murine dopaminergic neurons, pre-treatment with SC79 largely inhibited hydrogen peroxide (H2O2)-induced cell viability reduction, apoptosis and necrosis. SC79 activated Akt in the neuronal cells, which was required for its neuroprotection against H2O2. Inhibition of Akt activation (by MK-2206 or AT7867) or expression (by targeted short hairpin RNA) largely attenuated SC79-induced neuroprotection. Further, CRISPR-Cas9-mediated Akt1 knockout in SH-SY5Y cells abolished SC79-induced neuroprotective function against H2O2. Reversely, forced activation of Akt by the constitutively-active Akt1 mimicked SC79-induced anti-H2O2 activity. Together, we conclude that activation of Akt by SC79 protects dopaminergic neurons from H2O2.
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