Oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson's disease (PD). Considering the entwined relationship among these factors, epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its protective effects against those factors. The objective of this study is to determine whether EGCG protects N27 dopaminergic neuronal cells from H2O2- and TNF alpha-induced neurotoxicity. Seven treatments were included: control, H2O2, TNF alpha, FeSO4, H2O2+EGCG, TNF alpha+EGCG, FeSO4+ EGCG. Cells were pretreated with 10 mu M EGCG, followed by 50 mu M H2O2, 30 ng/ml TNF alpha or 50 mu M FeSO4. Neuroprotective effects of EGCG were assessed by cell viability assay, caspase-3 activity, intracellular reactive oxygen species (ROS) generation, and iron related protein expressions. Caspase-3 activity was increased to 2.8 fold (P < 0.001) and 1.5 fold (P < 0.01) with H2O2 and TNF alpha treatment; However, EGCG pretreatment significantly decreased the caspase activity by 50.2 % (P < 0.001) and 30.1 % (P < 0.05). Similarly, cell viability was reduced to 69.2 % (P < 0.01) and 89 % (P < 0.01) by H2O2 and TNF alpha, which was partially blocked by EGCG pretreatment. Also, EGCG significantly (P < 0.001) protected against H2O2-induced ROS in a time dependent manner. In addition, both H2O2 and TNF alpha significantly (P < 0.05) upregulated hepcidin expression and marginally reduced ferroportin (Fpn) expression unlike iron treatment alone. Collectively, our results show that EGCG protects against both TNF alpha- and H2O2-induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated mainly by hepcidin and partially by Fpn.
[1]Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA 50011 USA.
[2]Shanghai Univ Tradit Chinese Med, Sch Publ Hlth, Shanghai, Peoples R China.
[3]Iowa State Univ, Dept Biomed Sci, Ames, IA 50011 USA.
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