Downregulation of Smac attenuates H2O2-induced apoptosis via endoplasmic reticulum stress in human lens epithelial cells.
Downregulation of Smac attenuates H2O2-induced apoptosis via endoplasmic reticulum stress in human lens epithelial cells.
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Smac 下调可通过人晶状体上皮细胞内质网应激减弱 H2O2 诱导的细胞凋亡
DOI：
10.1097/md.0000000000007419
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发表时间：
2017-07
期刊：
影响因子：
1.6
通讯作者：
Guangying Z
中科院分区：
文献类型：
--
作者：
De-Qian K;Yue L;Li L;Guangying Z
据报道，第二种线粒体衍生的半胱天冬酶激活剂 (Smac) 可促进细胞凋亡。鉴于细胞凋亡在白内障发生过程中的重要作用，本研究的目的是探讨Smac是否通过内质网应激（ERS）诱导人晶状体上皮细胞（HLEC）凋亡。通过免疫组织化学方法检测了 157 名年龄相关性白内障患者和 5 名正常对照者晶状体前囊中的 Smac 表达。使用 HLEC 系中的小干扰 RNA 敲低进一步评估了 Smac 在过氧化氢 (H2O2) 诱导的 ERS 和细胞凋亡中的作用。值得注意的是，白内障患者的 Smac 表达显着高于对照组，但与白内障严重程度无关。细胞存活率与H2O2浓度呈负相关，且在200μmol/L时影响最显着。此外，流式细胞术显示，Smac 敲低可减弱 H2O2 诱导的细胞凋亡，并增强细胞凋亡和内质网相关标志物的表达，包括葡萄糖调节蛋白 78、C/EBP 同源蛋白、caspase 3、B 细胞慢性淋巴细胞白血病/淋巴瘤 2 相关 X 和 BCL2——基因和蛋白质水平。总的来说，这些结果表明 Smac 在 ERS 诱导的 HLEC 细胞凋亡中发挥重要作用，表明其与白内障的发生密切相关。
Second mitochondria-derived activator of caspases (Smac) is reported to promote apoptosis. Given the important role of apoptosis in cataract development, the aim of this study was to investigate whether Smac induces human lens epithelial cell (HLEC) apoptosis via endoplasmic reticulum stress (ERS). Smac expression was examined by immunohistochemistry in anterior lens capsules from 157 patients with age-related cataracts and 5 normal controls. The role of Smac in hydrogen peroxide (H2O2)-induced ERS and apoptosis was further evaluated using small interfering RNA knockdown in an HLEC line. Notably, Smac expression was significantly higher in patients with cataracts than in controls, but showed no association with cataract severity. Cell survival was inversely correlated with H2O2 concentration, and was most significantly affected at 200 μmol/L. Moreover, flow cytometry revealed that Smac knockdown attenuated H2O2-induced apoptosis and enhanced apoptotic- and endoplasmic reticulum-related marker expression—including that of glucose-regulated protein 78, C/EBP homologous protein, caspase 3, B-cell chronic lymphocytic leukemia/lymphoma 2-associated X, and BCL2—at the gene and protein level. Collectively, these results indicate that Smac plays an important role in ERS-induced apoptosis in HLECs, suggesting its close association with cataract development.