Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.
Mol Med Rep. 2018 May;17(5):7149-7155. doi: 10.3892/mmr.2018.8759. Epub 2018 Mar 16.
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.
胰岛 β 细胞损伤与糖尿病密切相关。然而,尽管缺氧被认为是导致胰岛 β 细胞损伤的主要原因之一,但导致胰岛 β 细胞损伤的确切机制尚不清楚。凋亡诱导因子是一种促进神经元凋亡的线粒体蛋白。迄今为止,关于凋亡诱导因子的研究主要集中在阿尔茨海默病上,研究表明,凋亡诱导因子在缺血再灌注大鼠脑中的表达显著增加,这表明其与缺氧密切相关。然而,凋亡诱导因子在对缺氧敏感的胰岛 β 细胞中的作用尚不清楚。因此,本研究旨在探讨凋亡诱导因子在缺氧环境下对胰岛 β 细胞的功能。使用氯化钴 (CoCl2) 模拟细胞的缺氧状态。末端脱氧核苷酸转移酶 dUTP 缺口末端标记法的结果表明,CoCl2 促进 MIN6 小鼠胰岛素瘤细胞凋亡,Western blot 和逆转录-定量聚合酶链反应结果表明,凋亡诱导因子被激活,促进线粒体损伤和 caspase 3 激活。使用短发夹 RNA 沉默凋亡诱导因子可显著减少 CoCl2 诱导的 MIN6 细胞凋亡。综上所述,CoCl2 增加了凋亡诱导因子的表达,加重了 MIN6 细胞中的线粒体损伤。因此,抑制凋亡诱导因子的表达可能有利于胰岛 β 细胞在胰岛移植过程中的存活。