文章摘要
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,2012,(9):1187~1191
PKR抑制胰岛β细胞生长的机制研究
Effect of PKR on proliferation of pancreatic β-cell
投稿时间:2012-05-31  
DOI:10.7655
中文关键词: 胰岛β细胞  BEPP  PKR  cyclin D1  细胞增殖
英文关键词: pancreatic β-cell  BEPP  PKR  cyclin D1  cell proliferation
基金项目:国家自然科学基金(81170714)
作者单位
陈珊珊 南京医科大学生物化学与分子生物学系,江苏 南京 210029
淮阴卫生高等职业技术学校生物教研室,江苏 淮安 223002 
王 怡 南京医科大学生物化学与分子生物学系,江苏 南京 210029 
顾丽泽 南京医科大学生物化学与分子生物学系,江苏 南京 210029 
高丽丽 南京医科大学生物化学与分子生物学系,江苏 南京 210029 
郭 军 南京医科大学生物化学与分子生物学系,江苏 南京 210029 
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中文摘要:
      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?
英文摘要:
      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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