SET7/9介导的内质网应激对砷致肝细胞凋亡的影响

摘要

AIM:To investigate the effect of SET7/9 (SET domain containing 7/9) -mediated endoplasmic reticulum stress (ERS) on protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, and to explore the mechanisms of arsenic-induced hepatocyte apoptosis.METHODS:Human liver LO2 cells were divided into control group, arsenic poisoning model group, negative transfection group and SET7/9 siRNA transfection group.The apoptosis of the LO2 cells in each group was analyzed by flow cytometry.The protein levels of SET7/9, glucose-regulated protein 78 (GRP78) , PERK and p-PERK in the LO2 cells of each group were observed by Western blot.RESULTS:Inhibition of SET7/9 expression reduced the apoptotic rate of arsenic-induced LO2 cells.Arsenic exposure increased the expression of SET7/9 in the LO2 cells.Arsenic exposure increased the protein levels of GRP78 and p-PERK in the LO2 cells, but decreased the protein levels of GRP78 and p-PERK after transfection with SET7/9 siRNA (P<0.05).CONCLUSION:Arsenic exposure induces hepatocyte apoptosis by increasing SET7/9 to activate ERS by PERK signaling pathway.%目的:通过研究SET7/9 (SET domain containing 7/9) 对内质网应激 (ERS) 的蛋白激酶R样内质网激酶 (PERK) 信号通路的影响, 探讨其在砷致肝细胞凋亡机制中的作用.方法:把人肝细胞LO2分为对照组、砷染毒模型组、阴性转染组和SET7/9 siRNA转染组.流式细胞术检测各组细胞凋亡的变化;Western blot方法观察各组LO2细胞SET7/9、葡萄糖调节蛋白78 (GRP78) 、PERK和p-PERK表达水平的变化.结果:抑制SET7/9表达可降低砷染毒LO2细胞的凋亡率 (P <0.05) .砷染毒可以使LO2细胞SET7/9表达水平升高, 上调LO2细胞GRP78和p-PERK的蛋白水平 (P <0.05) .砷染毒LO2细胞经SET7/9 siRNA转染后可下调其GRP78和p-PERK的蛋白水平.结论:砷可以通过上调SET7/9激活了ERS的PERK信号通路, 从而导致肝细胞凋亡.