Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress
Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress
复制标题
晚期糖基化终产物通过氧化应激诱导胰腺β细胞损伤
DOI：
10.1016/j.diabet.2012.01.003
复制
发表时间：
2012-06-01
影响因子：
7.2
通讯作者：
Su, Q.
中科院分区：
文献类型：
--
作者：
Lin, N.;Zhang, H.;Su, Q.
瞄准。本研究评价晚期糖基化终产物(AGEs)对胰岛β细胞的直接影响，包括细胞活力、活性氧(ROS)的产生和胰岛素的分泌，并寻找AGEs对INS-1细胞产生ROS的主要来源和AGE损伤细胞的可能分子机制(S)。-INS-1细胞分别加入100、200、500 mg/L的AGEs培养不同时间。采用ELISA法和实时荧光定量聚合酶链式反应(Real-time PCR)检测细胞凋亡率。DCFH-DA和MitoSOX Red探针用流式细胞仪检测ROS，荧光素化学发光法检测NADPH氧化酶活性，Western印迹法检测MAPK的磷酸化。-在AGE处理的细胞中，细胞凋亡和ROS的产生都以剂量依赖的方式增加，线粒体电子传输链和NADPH氧化酶途径都参与了ROS的产生，尽管线粒体途径的作用更早和更重要。AGEs对胰岛素分泌有毒性作用，这种毒性作用可通过抑制ROS而在很大程度上被逆转。-AGEs主要通过线粒体途径氧化应激损伤INS-1细胞，尽管JNK和p38MAPK信号通路也是ROS介导的β细胞死亡的关键调节器。(C)2012年爱思唯尔·马森公司。版权所有。
Aim. - This study evaluated the direct effects of advanced glycation end-products (AGEs) on pancreatic beta cells, including cellular viability, generation of reactive oxygen species (ROS) and insulin secretion, and also looked for the main source of ROS in INS-1 cells and the possible molecular mechanism(s) of cell injury by AGEs.Methods. - INS-1 cells were cultured with 100, 200 and 500 mg/L of AGEs for specific periods of time. Cell apoptosis was determined by ELISA and real-time PCR assays. ROS were detected by DCFH-DA and MitoSOX Red probes with a flow cytometer, NADPH oxidase activity was measured by lucigenin chemiluminescence and MAPK phosphorylation was measured by Western blot tests.Results. - Both cell apoptosis and ROS generation increased in AGE-treated cells in a dose-dependent way, and both the mitochondrial electron transport chain and NADPH oxidase pathway participated in ROS generation, although the role of the mitochondrial pathway was earlier and more important. AGEs exerted a toxic effect on insulin secretion that could be largely reversed by inhibiting ROS.Conclusion. - AGEs injured INS-1 cells by oxidative stress mainly through the mitochondrial pathway, although the JNK and p38 MAPK signaling pathways were also key modulators in ROS-mediated beta-cell death. (C) 2012 Elsevier Masson SAS. All rights reserved.