Selenoprotein S silencing triggers mouse hepatoma cells apoptosis and necrosis involving in intracellular calcium imbalance and ROS-mPTP-ATP

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 10; pp. 2113 - 2123
• Main Authors: Li, Xiaojing, Chen, Menghao, Yang, Zijiang, Wang, Wei, Lin, Hongjin, Xu, Shiwen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2018
• Subjects: adenosine triphosphate; Apoptosis; Ca2+ homeostasis; calcium; endoplasmic reticulum; hepatoma; homeostasis; mice; mitochondria; Necrosis; reactive oxygen species; ROS; selenoproteins; SelenoS; Ca2+ homeostasis; SelenoS; ROS; Apoptosis; Necrosis; Ca(2+) homeostasis
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2018.07.005

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 Hepa1-6 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 ΔΨm, ATP, and apoptosis and necrosis rates. SelenoS silencing broke the intracellular calcium homeostasis, induced mitochondrial dynamic disorder, ROS accumulation, loss of ΔΨm and ATP, and triggered apoptosis and necrosis in mouse hepatoma cells. The clearance of ROS alleviated the loss of ΔΨm and ATP caused by silencing of SelenoS, reduced cell necrosis and increased apoptosis. However, SelenoS silencing did not cause ER stress in Hepa1-6 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. •SelenoS silencing induces apoptosis and necrosis of mouse hepatoma cells.•SelenoS silencing induces ER Ca2+ outflow to cytoplasm and mitochondria.•ROS-mPTP-ATP participates in cell death transformation from apoptosis to necrosis.