Journal
TOXICOLOGY MECHANISMS AND METHODS
Volume 27, Issue 8, Pages 598-608Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/15376516.2017.1339155
Keywords
Arsenite; luteolin; apoptosis; alpha-synuclein; Parkinson's disease
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Funding
- Foundation and Frontier Research Program of Chongqing Municipal Science and Technology Commission [cstc2016jcyjA0223, cstc2016jcyjA0435]
- Science and Technology Research Program of Chongqing Education Commission [KJ1600204]
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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 c-H2AX expression. Our results further showed the expression of alpha-Synuclein (alpha-Syn) was significantly increased in arsenite-treated cells, but co-treatment with luteolin reversed the expression of alpha-Syn back toward normal level. Inhibition of alpha-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 alpha-Syn, and indicating that luteolin may be developed as a chemopreventive supplementary agent to ameliorate dopaminergic cell apoptosis resulting from arsenite exposure.
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