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.
[1]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Neurol, Shanghai 200062, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Emergency Internal Med, Shanghai 200062, Peoples R China.
[3]Fudan Univ, Inst Integrat Med, Zhongshan Hosp, Lab Neurol, Shanghai 200032, Peoples R China.
[4]Fudan Univ, Zhongshan Hosp, Dept Integrat Med, Shanghai 200032, Peoples R China.
[5]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr Translat Neurodegenerat & Regenerat Therapy, Shanghai 200072, Peoples R China.
[6]Tongji Univ, Dept Immunol, Sch Med, Shanghai 200092, Peoples R China.
(8.0+极速模式)