Oncotarget

Research Papers:

SC79 protects dopaminergic neurons from oxidative stress

Yan Xu _, Ya-Wen Gao, Yu Yang

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2018; 9:12639-12648. https://doi.org/10.18632/oncotarget.23538

Metrics: PDF 222 views  |   HTML 530 views  |   ?  


Abstract

Yan Xu1, Ya-Wen Gao1 and Yu Yang1

1Geriatrics Department, The Second Xiang Ya Hospital of Central South University, Changsha, China

Correspondence to:

Yan Xu, email: xuyanxydr@163.com, xuyan217@csu.edu.cn

Keywords: SC79; Akt; dopaminergic neurons; oxidative stress

Received: November 02, 2017     Accepted: December 01, 2017     Published: December 20, 2017

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23538