title: Echinacoside Protects Against MPP(+)-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation.
abstract: 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.
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. qingzhao2010@hotmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Emergency Internal Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Neurology, Institute of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Cai
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated with Tongji University School of Medicine, Shanghai, 200072, China.|Department of Immunology, Tongji University School of Medicine, Shanghai, 200092, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated with Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Kaizhe
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. baiyu_bb@sina.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; D004791:Enzyme Inhibitors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006027:Glycosides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; C060297:echinacoside; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-Methyl-4-phenylpyridinium ion; ATF3; CHOP; Echinacoside; Parkinson’s disease; Reactive oxygen species