Echinacoside Protects Against MPP-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation.

Echinacoside (ECH) is protective in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenylpyridinium ion (MPP). To investigate the mechanisms involved, SH-SY5Y neuroblastoma cells were treated with MPP or a combination of MPP and ECH, and the expression of ATF3 (activating transcription factor 3), CHOP (C/EBP-homologous protein), SCNA (synuclein alpha), and GDNF (glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP-induced reactive oxygen species (ROS). In addition, ECH suppressed the ROS and MPP-induced expression of apoptotic genes ( ATF3, CHOP, and SCNA). ECH markedly decreased the MPP-induced caspase-3 activity in a dose-dependent manner. ATF3-knockdown also decreased the CHOP and cleaved caspase-3 levels and inhibited the apoptosis induced by MPP. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP. ECH also improved dopaminergic neuron survival during MPP treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP-induced apoptosis in PD. [ABSTRACT FROM AUTHOR]