Cholesterol induces mitochondrial dysfunction and apoptosis in mouse pancreatic beta-cell line MIN6 cells
Cholesterol induces mitochondrial dysfunction and apoptosis in mouse pancreatic beta-cell line MIN6 cells
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DOI：
10.1007/s12020-009-9275-y
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发表时间：
2010-02-01
期刊：
影响因子：
3.7
通讯作者：
Chen, Chen
中科院分区：
文献类型：
--
作者：
Zhao, Yu-Feng;Wang, Li;Chen, Chen
胰腺β细胞质量的减少是导致2型糖尿病的关键因素。肥胖和超重与高水平的脂质，包括胆固醇，与2型糖尿病密切相关。然而，胆固醇对胰腺β细胞的直接影响尚未得到广泛研究。在这项研究中，使用MIN 6小鼠β细胞系来测试胆固醇在不同剂量和时间内对胰腺β细胞凋亡的影响。结果发现，胆固醇剂量和时间依赖性诱导细胞死亡的MIN 6细胞超过160 μ M后，在体外处理6小时。Annexin-V染色显示胆固醇处理显著诱导MIN 6细胞凋亡。胆固醇处理导致保留罗丹明123的能力丧失，表明MIN 6细胞中的线粒体损伤。低温条件可阻断胆固醇诱导的细胞凋亡和线粒体损伤。此外，谷胱甘肽还保护MIN 6细胞免受胆固醇诱导的细胞死亡。结论：高胆固醇诱导MIN 6细胞凋亡，部分原因是线粒体功能障碍。我们认为，β细胞中胆固醇的过度摄取可能导致β细胞凋亡和功能障碍以及2型糖尿病的恶化。
Reduction of pancreatic beta-cell mass is a key element leading to type 2 diabetes. Obesity and overweight with high levels of lipids including cholesterol are tightly linked to type 2 diabetes. The direct impact of cholesterol on pancreatic beta-cells, however, has not been extensively studied. In this study, MIN6 mouse beta-cell line was used to test the effect of cholesterol on pancreatic beta-cell apoptosis over different doses and durations. It was found that cholesterol dose- and time-dependently induced cell death of MIN6 cells above 160 mu M after 6 h treatment in vitro. Annexin-V staining revealed that cholesterol treatment significantly induced apoptosis in MIN6 cells. Cholesterol treatment resulted in the loss of the ability to retain Rhodamine 123, indicating mitochondrial damage in MIN6 cells. Cholesterol-induced cell apoptosis and mitochondrial damage were blocked by low-temperature condition. In addition, glutathione also protected MIN6 cells from cholesterol-induced cell death. It is concluded that high level of cholesterol induces cell apoptosis in MIN6 cells, which is in part due to mitochondrial dysfunction. We suggest that excessive uptake of cholesterol in beta-cells may contribute to beta-cell apoptosis and dysfunction and the deterioration of type 2 diabetes.