Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating GRP78 in SH-SY5Y cells

被引:35
作者
Huang, Jingwei [1 ,2 ]
Chen, Changyan [2 ]
Gu, Hua [2 ]
Li, Chen [2 ]
Fu, Xing [3 ]
Jiang, Ming [2 ,3 ]
Sun, Hui [1 ,2 ,3 ]
Xu, Jun [1 ]
Fang, Jianmin [2 ,3 ]
Jin, Lingjing [1 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Tongji Hosp, Dept Neurol, 389 Xincun Rd, Shanghai 200065, Peoples R China
[2] Tongji Univ, Sch Life Sci & Technol, 1239 Siping Rd, Shanghai 200092, Peoples R China
[3] Tongji Univ, Suzhou Inst, Biomed Res Ctr, Bldg 2,198 Jinfeng Rd, Suzhou 215101, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
GRP78; MANF; Parkinson's disease; SH-SY5Y; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ALPHA-SYNUCLEIN; NEURON LOSS; RAT MODEL; DEATH; OVEREXPRESSION; PROLIFERATION; MANF; GDNF;
D O I
10.1002/cbin.10621
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects dopaminergic neurons from damage. In this study, we used MTT, immunohistochemistry, and TUNEL staining to investigate the protective effect of MANF in SH-SY5Y cells treated with 6-OHDA or overexpressed alpha-synuclein. Cleaved caspase-3 levels significantly increased in cells treated with 6-OHDA or overexpressed a-synuclein. 6-OHDA or a alpha-synuclein overexpression that induced cleaved caspase-3 levels to increase was reduced by MANF treatment. In addition, MANF treatment upregulated GRP78 expressions in cells treated with 6-OHDA or overexpressed alpha-synuclein, and RNAi knockdown for GRP78 could block the MANF induced cell survival from 6-OHDA treatment. Furthermore, GRP78 overexpression inhibited 6-OHDA-induced apoptosis. Our data suggest that MANF inhibits apoptosis induced by 6-OHDA and overexpressed a-synuclein in SH-SY5Y cells via upregulating GRP78 in the transcriptional pattern.
引用
收藏
页码:803 / 811
页数:9
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