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

作　　者：Qing Zhao Xiaoyan Yang Dingfang Cai Ling Ye Yuqing Hou Lijun Zhang Jiwei Cheng Yuan Shen Kaizhe Wang Yu Bai 

机构地区：[1]Department of Neurology, Putuo Hospital,Shanghai University of Traditional Chinese Medicine [2]Department of Emergency Internal Medicine, Putuo Hospital,Shanghai University of Traditional Chinese Medicine [3]Laboratory of Neurology, Institute of Integrative Medicine,Zhongshan Hospital, Fudan University [4]Department of Integrative Medicine, Zhongshan Hospital,Fudan University [5]Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated with Tongji University School of Medicine [6]Department of Immunology, Tongji University School of Medicine

出　　处：《Neuroscience Bulletin》2016年第4期349-362,共14页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81202814);the Shanghai Municipal Commission of Health and Family Planning(20124y116);the Young Teachers Training Funding Scheme of Shanghai Colleges and Universities,China(zzszy12026)

摘　　要：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-SYSY neuroblastoma ceils 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 cas- pase-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.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-SYSY neuroblastoma ceils 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 cas- pase-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.

关 键 词：ECHINACOSIDE Parkinson＇s disease 1-Methyl-4-phenylpyridinium ion. Reactive oxygen species ATF3 CHOP 

分 类 号：R742.5[医药卫生—神经病学与精神病学]