文章摘要
宋成洁,王 敏,汤韫祎,郑 月.ISRIB对Aβ1⁃42诱导的SH⁃SY5Y细胞的神经保护作用[J].南京医科大学学报,2019,(12):1712~1715
ISRIB对Aβ1⁃42诱导的SH⁃SY5Y细胞的神经保护作用
The neuroprotective effect of ISRIB on SH⁃SY5Y cells induced by Aβ1⁃42
投稿时间:2019-07-19  
DOI:10.7655/NYDXBNS20191202
中文关键词: 阿尔茨海默病  内质网应激  eIF2α  β⁃淀粉样蛋白
英文关键词: Alzheimer’s disease  endoplasmic reticulum stress  eukaryotic initiation factor 2α  amyloid β⁃amyloid
基金项目:国家自然科学基金(81703184)
作者单位
宋成洁 徐州医科大学生理学系江苏 徐州 221004
南京医科大学生物化学与分子生物学系江苏 南京 210029 
王 敏 南京医科大学病理学系江苏 南京 210029 
汤韫祎 南京医科大学病理学系江苏 南京 210029 
郑 月 南京医科大学生物化学与分子生物学系江苏 南京 210029 
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中文摘要:
      目的:以β淀粉样蛋白(amyloid β?protein 1?42,Aβ1?42)诱导的SH?SY5Y细胞为模型,探讨综合应激反应抑制剂(inte? grated stress response inhibitor,ISRIB)对 Aβ1?42诱的内质网应激和细胞凋亡的影响。方法:SH?SY5Y细胞按不同处理方式分为4组:对照组、Aβ组、ISRIB组、ISRIB+Aβ组。培养48 h后用噻唑蓝比色法检测各组细胞存活率,蛋白免疫印迹试验检测内质网应激相关蛋白的表达,包括葡萄糖调节蛋白78(glucose?regulated protein 78,GRP78)、蛋白激酶R样内质网激酶(protein ki?nase R?like ER kinase,PERK)?真核起始因子 2α(eukaryotic initiation factor 2α,eIF2α)?活化转录因子 4(activation transcription factor4,ATF4)介导的内质网应激通路,以及下游的CCAAT/增强子结合蛋白同源蛋白(C/EBP homologous protein,CHOP),同时也检测了凋亡相关蛋白的表达,包括Bcl?2、Bax、cleaved?caspase?3。结果:与Aβ组比较,ISRIB能显著提高SH?SY5Y细胞的存活率(P <0.01),显著降低p?PERK(P < 0.01)、p?eIF2α(P <0.05)、ATF4(P < 0.01)和CHOP的表达(P < 0.05),提高Bcl?2/Bax表 达(P < 0.05),降低cleaved?caspase?3表达(P < 0.01)。 结论:ISRIB能够抑制Aβ1?42诱导的SH?SY5Y细胞凋亡,其机制与抑制ERS造成的 eIF2α通路激活及其相关凋亡信号通路有关。
英文摘要:
      Objective:This study aims to investigate the effect of integrated stress response inhibitor(ISRIB)in apoptosis and endoplasmic reticulum stress of SH?SY5Y cells induced by amyloid β?amyloid protein1?42(Aβ1?42)and to clarify its mechanism. Methods:SH?SY5Y cells were divided into normal control group,Aβ group,ISRIB group and ISRIB+Aβ group. The survival rate of cells in each group was detected by MTT colorimetric assay. Western blotting was used to examine the expression of endoplasmic reticulum stress marker glucose?regulated protein 78(GRP78)and activation of protein kinase R?like ER kinase(PERK)?eukaryotic initiation factor 2α(eIF2α)?activation transcription factor 4(ATF4)signaling pathway,together with C/EBP homologous protein(CHOP). Meanwhile,apoptosis?related proteins were also detected,including Bcl?2、Bax and cleaved?caspase3. Results:Compared with Aβ group,ISRIB significantly increased the survival rate of SH?SY5Y cells(P < 0.01),significantly decreased the activation of p?PERK(P < 0.01),p?eIF2α(P<0.05),ATF4(P < 0.05)and CHOP(P < 0.05),increased Bcl?2/Bax level(P < 0.05)and decreased cleaved?casepase3 expression(P < 0.01). Conclusion:ISRIB could inhibit the apoptosis of SH?SY5Y cells induced by Aβ1?42,and its mechanism is related to the inhibiting the activation of eIF2α pathway and apoptotic signaling pathway induced by ERS.
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