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 treat...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.展开更多
目的:探讨利福平对帕金森病致病蛋白α-突触共核蛋白(α-synuc le in)聚集的影响,以及对1-甲基-4-苯基-吡啶离子(MPP+)诱导的细胞损伤的拮抗作用。方法:选用大鼠嗜铬细胞瘤株PC12细胞,利用MPP+诱导建立帕金森病细胞模型,利福平进行干预...目的:探讨利福平对帕金森病致病蛋白α-突触共核蛋白(α-synuc le in)聚集的影响,以及对1-甲基-4-苯基-吡啶离子(MPP+)诱导的细胞损伤的拮抗作用。方法:选用大鼠嗜铬细胞瘤株PC12细胞,利用MPP+诱导建立帕金森病细胞模型,利福平进行干预;采用MTT法检测细胞活性、W estern b lotting法检测α-synuc le-in表达及聚集,流式细胞仪检测细胞凋亡。结果:1 mmol/LMPP+组细胞活性明显低于对照组,细胞凋亡率和α-sy-nuc le in表达及聚集高于对照组;预先经过100、200和300μmol/L各浓度利福平处理后,MPP++利福平组细胞活性明显高于1 mmol/L MPP+组,而细胞凋亡率和α-synuclein表达及聚集均低于1 mmol/L MPP+组,并具有明显的剂量-效应关系。结论:利福平能够抑制α-synuclein的表达及聚集,并对MPP+诱导的PC12细胞损伤具有拮抗作用。展开更多
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)
文摘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.
文摘目的:探讨利福平对帕金森病致病蛋白α-突触共核蛋白(α-synuc le in)聚集的影响,以及对1-甲基-4-苯基-吡啶离子(MPP+)诱导的细胞损伤的拮抗作用。方法:选用大鼠嗜铬细胞瘤株PC12细胞,利用MPP+诱导建立帕金森病细胞模型,利福平进行干预;采用MTT法检测细胞活性、W estern b lotting法检测α-synuc le-in表达及聚集,流式细胞仪检测细胞凋亡。结果:1 mmol/LMPP+组细胞活性明显低于对照组,细胞凋亡率和α-sy-nuc le in表达及聚集高于对照组;预先经过100、200和300μmol/L各浓度利福平处理后,MPP++利福平组细胞活性明显高于1 mmol/L MPP+组,而细胞凋亡率和α-synuclein表达及聚集均低于1 mmol/L MPP+组,并具有明显的剂量-效应关系。结论:利福平能够抑制α-synuclein的表达及聚集,并对MPP+诱导的PC12细胞损伤具有拮抗作用。
