Selenoprotein S silencing triggers mouse hepatoma cells apoptosis and necrosis involving in intracellular calcium imbalance and ROS-mPTP-ATP
Selenoprotein S silencing triggers mouse hepatoma cells apoptosis and necrosis involving in intracellular calcium imbalance and ROS-mPTP-ATP
复制标题
硒蛋白S沉默引发小鼠肝癌细胞凋亡和坏死，涉及细胞内钙失衡和ROS-mPTP-ATP
DOI：
10.1016/j.bbagen.2018.07.005
复制
发表时间：
2018-10-01
影响因子：
3
通讯作者：
Xu, Shiwen
中科院分区：
文献类型：
--
作者：
Li, Xiaojing;Chen, Menghao;Xu, Shiwen
硒蛋白S（Selenoprotein S，SelenoS）是一种位于细胞内质网（endoplasmic reticulum，ER）和细胞膜上的硒蛋白，具有抗氧化、抗凋亡和抗ER应激等功能。为探讨SelenoS基因沉默对小鼠肝癌细胞死亡的影响及SelenoS在细胞内的生物学功能，我们敲低了Hepal-6细胞中的SelenoS基因，检测了细胞内质网应激、细胞内钙稳态、线粒体动力学、凋亡和坏死。为了进一步探讨活性氧（ROS）是否对SelenoS沉默下的细胞凋亡和坏死有影响，我们使用NAC（2.5 mM）预处理细胞，并检测Δ Psim、ATP以及凋亡和坏死率。SelenoS基因沉默可破坏小鼠肝癌细胞内钙稳态，导致线粒体动力学紊乱、ROS积累、Δ Psim和ATP丢失，并引发细胞凋亡和坏死。ROS的清除减轻了SelenoS沉默引起的Delta Psim和ATP的丢失，减少了细胞坏死，增加了细胞凋亡。然而，SelenoS沉默在Hepal-6细胞中不引起ER应激。这些结果表明，硒沉默通过影响细胞内钙稳态而触发小鼠肝癌细胞凋亡和坏死，ROS-mPTP-ATP参与了细胞由凋亡向坏死转化的死亡过程，增加了损伤。
Selenoprotein S (SelenoS) is one of the cellular endoplasmic reticulum (ER) and membrane located selenoproteins, and it has the main functions of anti-oxidation, anti-apoptosis and anti-ER stress. To investigate the effect of SelenoS silencing on mouse hepatoma cell death and the intracellular biological function of SelenoS, we knocked down SelenoS in Hepal-6 cells, and detected ER stress, intracellular calcium homeostasis, mitochondrial dynamics, apoptosis and necrosis. To further explore whether reactive oxygen species (ROS) has an effect on apoptosis and necrosis under SelenoS silencing, we used NAC (2.5 mM) to pretreat cells, and detected Delta Psi m, ATP, and apoptosis and necrosis rates. SelenoS silencing broke the intracellular calcium homeostasis, induced mitochondrial dynamic disorder, ROS accumulation, loss of Delta Psi m and ATP, and triggered apoptosis and necrosis in mouse hepatoma cells. The clearance of ROS alleviated the loss of Delta Psi m and ATP caused by silencing of SelenoS, reduced cell necrosis and increased apoptosis. However, SelenoS silencing did not cause ER stress in Hepal-6 cells. These results indicate that SelenoS silencing triggers mouse hepatoma cells apoptosis and necrosis through affecting intracellular calcium homeostasis and ROS-mPTP-ATP participates in cell death transformation from apoptosis to necrosis to rise damage.