Overexpression of appoptosin promotes mitochondrial damage in MIN6 cells

Abstract

Damage to pancreatic β-cells is closely associated with diabetes. However, the mechanism underlying injury to pancreatic β-cells remains unclear, although hypoxia is considered as one of the leading causes. Appoptosin is a mitochondrial protein that promotes neuronal apoptosis. Studies conducted on appoptosin thus far have primarily focused on Alzheimer's disease, and have demonstrated that the expression of appoptosin is significantly increased in ischemic-reperfused rat brains, which indicates its close association with hypoxia. However, the role of appoptosin in pancreatic β-cells, which are sensitive to hypoxia, remains unknown. Therefore, the current study aimed to investigate the function of appoptosin in pancreatic β-cells in a hypoxic environment. Cobalt chloride (CoCl2) was used to mimic the hypoxic status of the cells. The results of a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay demonstrated that CoCl2 promoted apoptosis in MIN6 mouse insulinoma cells, and western blotting and reverse transcription-quantitative polymerase chain reaction results demonstrated that the activation of appoptosin was induced, promoting mitochondrial damage and caspase 3 activation. Silencing of appoptosin using short hairpin RNA significantly reduced CoCl2-induced apoptosis in MIN6 cells. In conclusion, CoCl2 increased the expression of appoptosin, which aggravated mitochondrial damage in MIN6 cells. Therefore, inhibiting the expression of appoptosin may benefit pancreatic β-cells survival during islet transplantation.