Inhibition of α-Synuclein contributes to the ameliorative effects of dietary flavonoids luteolin on arsenite-induced apoptotic cell death in the dopaminergic PC12 cells

Abstract

Arsenite is a toxic metalloid that may increase the risk of Parkinson’s disease by inducing dopaminergic neuronal apoptosis. Luteolin, a common dietary flavonoid, possesses variety of biological functions, but potential effects of luteolin on arsenite toxicity remain elusive. In this study, we demonstrated that luteolin prevented arsenite-induced apoptosis in the dopaminergic PC12 cells. Administration of luteolin to cells attenuated arsenite-induced ROS production, enhanced caspase-3 activity and γ-H2AX expression. Our results further showed the expression of α-Synuclein (α-Syn) was significantly increased in arsenite-treated cells, but co-treatment with luteolin reversed the expression of α-Syn back toward normal level. Inhibition of α-Syn by siRNA remarkably enhanced the beneficial effect of luteolin against arsenite-induced apoptotic cell death. Taken together, these results demonstrate that the ameliorative effects of luteolin against arsenite in the dopaminergic cell may be modulated by α-Syn, and indicating that luteolin may be developed as a chemopreventive supplementary agent to ameliorate dopaminergic cell apoptosis resulting from arsenite exposure.

Keywords:

• Arsenite
• luteolin
• apoptosis
• α-synuclein
• Parkinson’s disease

Acknowledgements

The authors appreciated the generous gift of PC12 cells from Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, China.

Disclosure statement

The authors deny any competing interests related to this study.

Additional information

Funding

This research was supported by Foundation and Frontier Research Program of Chongqing Municipal Science and Technology Commission (Grant Number: cstc2016jcyjA0223 and cstc2016jcyjA0435), Science and Technology Research Program of Chongqing Education Commission (Grant Number: KJ1600204).