PKR抑制胰岛β细胞生长的机制研究
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国家自然科学基金(81170714)


Effect of PKR on proliferation of pancreatic β-cell
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    摘要:

    目的:探讨PKR激活诱导的胰岛β细胞生长抑制及其相关分子机制-方法:采用PKR激动剂BEPP处理INS-1细胞,MTT法检测其对细胞活力的影响;EdU荧光标记结合流式细胞术测定胰岛β细胞增殖及细胞周期变化;免疫印迹技术评价PKR下游信号分子eIF2α蛋白及其磷酸化水平变化,并检测细胞周期相关蛋白cyclin D1的表达-结果:MTT显示BEPP呈剂量和时间依赖性抑制INS-1细胞生长活力(P < 0.05);EdU荧光标记显示细胞增殖显著下降;流式细胞术表明BEPP处理组G1期细胞比例明显升高,而S期细胞比例显著下降(P < 0.05);Western blot结果表明:BEPP能下调eIF2α磷酸化而不是其蛋白水平,同时伴随cyclin D1蛋白含量显著降低(P < 0.05)-结论:PKR激活剂BEPP能诱导eIF2α磷酸化,阻断蛋白合成,且通过下调cyclin D1蛋白水平,诱导胰岛β细胞G1期阻滞,抑制其增殖,从而导致机体胰岛β细胞整体功能的失代偿和2型糖尿病的发生-

    Abstract:

    Objective:To investigate PKR activation-induced pancreatic β cell growth inhibition and its underlying molecular mechanisms. Methods:BEPP was used to activate PKR in INS-1 cells,cell viability was assessed by MTT assay. EdU labeling together with flow cytometry was applied to detect β-cell proliferation and cell cycle progression. Western blot assay was used to detect the expression of eIF2α and its phosphorylation and the expression of cyclin D1. Results:BEPP significantly inhibited the viability of INS-1 cells in a time and dose-dependent manner(P < 0.05). EdU labeling assay indicated a significant reduction on proliferation of β-cell(P < 0.05). Cell number in G0/G1 phase was increased and that in S phase was decreased (P < 0.05). Treatment with BEPP led to an increase in phosphorylation of eIF2α and a decreased expression of cyclin D1. Conclusion:BEPP (PKR inducer) could phosphorylate eIF2α which leads to inhibition of protein synthesis,at the same time,it can inhibit pancreatic β-cell proliferation through cell cycle arrest at G1 phase by downregulation of cyclin D1. Therefore,it can lead to the overall functions of the body of islet β-cell decompensation and the occurrence of type 2 diabetes.

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陈珊珊,王 怡,顾丽泽,高丽丽,郭 军. PKR抑制胰岛β细胞生长的机制研究[J].南京医科大学学报(自然科学版),2012,(9):1187-1191

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  • 收稿日期:2012-05-31
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