中国药理学通报Issue(6)：810-814,815,6.DOI:10.3969/j.issn.1001-1978.2015.06.015
中脑星形胶质细胞来源的神经营养因子对糖氧剥夺/再灌注诱导的SH-SY5 Y细胞损伤的保护作用
Protective effects of MANF on oxygen-glucose deprivation/reperfusion-induced apoptotic ER stress in SH-SY5 Y neural cells
摘要
Abstract
Aim To investigate the protective effects of MANF on human neuroblastoma SH-SY5 Y cells suf-fering from oxygen-glucose deprivation/reperfusion ( OGD/R) and the underlying mechanism. Methods SH-SY5Y cells were treated with OGD for 6 h, fol-lowed by reperfusion for 12 h. Meanwhile, the cells were incubated with 2 μmol · L-1 recombinant human protein MANF for 12 h during reperfusion. The cell morphology was observed under an optical microscope. The cell viability was determined by MTT assay. PI <br> staining was performed to detect the number of dead cells. Western blot was performed to determine the protein levels of endogenous MANF, glucose-related protein 78 ( GRP78/BiP) , phosphorylated inositol re-quiring enzyme 1 ( p-IRE1 ) , phosphorylated eukaryot-ic translation initiator factor 2α ( p-eIF2α) , cleaved caspase-3, and C/EBP-homologous protein (CHOP). Results The cells exposed to OGD/R became smaller and round, and the neurites of the cells were shortened or disappeared . Recombinant human protein MANF <br> improved the survival rate ( P <0. 05 ) and decreased the death rate ( P <0. 05 ) of SH-SY5 Y cells treated with by OGD/R. Western blot assay showed that the endoplasmic reticulum ( ER) stress-associated proteins GRP78/BiP, p-IRE1, p-eIF2α, and MANF were in-creased significantly after OGD/R treatment, compared with the untreated controls. However, the increases of secretion levels of apoptosis-associated proteins CHOP <br> and cleaved caspase-3 in SH-SY5 Y cells induced by OGD/R were significantly suppressed by MANF. Con-clusion OGD/R up-regulates the ER stress-associated proteins and causes apoptosis. MANF inhibits OGD/R-induced cell death, which may be related to attenua-ting ER stress-induced apoptosis.关键词
糖氧剥夺/再灌注/内质网应激/凋亡/MANF/非折叠Key words
OGD/R/ER stress/apoptosis/MANF/UPR/neuroprotection分类
医药卫生引用本文复制引用
孙瑞,刘珺,沈玉君,沙曼琪,徐胜春,沈玉先..中脑星形胶质细胞来源的神经营养因子对糖氧剥夺/再灌注诱导的SH-SY5 Y细胞损伤的保护作用[J].中国药理学通报,2015,(6):810-814,815,6.基金项目
国家自然科学基金资助项目( No 81173074,91129729,81372576) （ No 81173074,91129729,81372576）
