Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes.
Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes.
复制标题
DOI：
10.1007/s00125-010-1770-4
复制
发表时间：
2010-08
期刊：
影响因子：
8.2
通讯作者：
Dillmann, W. H.
中科院分区：
文献类型：
--
作者：
Makino, A.;Scott, B. T.;Dillmann, W. H.
线粒体经常通过融合和分裂改变其形状，这些形态学动力学在线粒体功能和发育以及程序性细胞死亡中起重要作用。本研究的目的是研究：（1）从糖尿病小鼠中分离的小鼠冠状动脉内皮细胞（MCEC）中的线粒体是否表现出增加的碎片化;（2）用超氧阴离子（O2 −）清除剂长期治疗对MCEC中的线粒体碎片化有有益的影响。MCEC新鲜分离并裂解用于蛋白质测量，或培养以确定线粒体形态和O2 −产生。对于离体高脂血症实验，使用人冠状动脉内皮细胞。从对照小鼠分离的MCEC中观察到线粒体小管延长，而糖尿病小鼠MCEC中的线粒体表现出增强的碎片化。在糖尿病小鼠MCEC中，导致线粒体融合的视神经萎缩1（OPA 1）蛋白水平显著降低，而导致线粒体分裂的动力蛋白相关蛋白1（DRP 1）水平显著增加。与对照MCEC相比，糖尿病MCEC在胞浆和线粒体中表现出显著更高的O2 −浓度。向糖尿病小鼠施用O2 −清除剂TEMPOL 4周导致线粒体碎片显著减少，而不改变MCEC中OPA 1和DRP 1蛋白的水平。高糖处理24 h明显诱导线粒体断裂，TEMPOL处理后线粒体断裂恢复。此外，细胞质或线粒体中过量的O2 −产生，显著增加了线粒体碎片化。这些数据表明，降低O2 −浓度可以恢复线粒体的形态学变化，并可能有助于改善糖尿病MCEC的线粒体功能。本文的在线版本（doi：10.1007/s 00125 -010-1770-4）包含补充材料，可供授权用户使用。
Mitochondria frequently change their shapes by fusion and fission and these morphological dynamics play important roles in mitochondrial function and development as well as programmed cell death. The goal of this study is to investigate whether: (1) mitochondria in mouse coronary endothelial cells (MCECs) isolated from diabetic mice exhibit increased fragmentation; and (2) chronic treatment with a superoxide anion (O2 −) scavenger has a beneficial effect on mitochondrial fragmentation in MCECs. MCECs were freshly isolated and lysed for protein measurement, or cultured to determine mitochondrial morphology and O2 − production. For the ex vivo hyperglycaemia experiments, human coronary endothelial cells were used. Elongated mitochondrial tubules were observed in MCECs isolated from control mice, whereas mitochondria in MCECs from diabetic mice exhibited augmented fragmentation. The level of optic atrophy 1 (OPA1) protein, which leads to mitochondrial fusion, was significantly decreased, while dynamin-related protein 1 (DRP1), which leads to mitochondrial fission, was significantly increased in MCECs from diabetic mice. Diabetic MCECs exhibited significantly higher O2 − concentrations in cytosol and mitochondria than control MCECs. Administration of the O2 − scavenger TEMPOL to diabetic mice for 4 weeks led to a significant decrease in mitochondrial fragmentation without altering the levels of OPA1 and DRP1 proteins in MCECs. High-glucose treatment for 24 h significantly induced mitochondrial fragmentation, which was restored by TEMPOL treatment. In addition, excess O2 − production, either in cytosol or in mitochondria, significantly increased mitochondrial fragmentation. These data suggest that lowering the O2 − concentration can restore the morphological change in mitochondria and may help improve mitochondrial function in diabetic MCECs. The online version of this article (doi:10.1007/s00125-010-1770-4) contains supplementary material, which is available to authorised users.
登录
查看更多内容
影响因子：
7.7
作者：
Bach, D;Naon, D;Zorzano, A
通讯作者：
Zorzano, A
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
9.9
作者：
Kim, JY;Hwang, JM;Park, SS
通讯作者：
Park, SS
影响因子：
34.7
作者：
Knott, Andrew B.;Perkins, Guy;Schwarzenbacher, Robert;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella
影响因子：
5.5
作者：
Makino, Ayako;Platoshyn, Oleksandr;Dillmann, Wolfgang H.
通讯作者：
Dillmann, Wolfgang H.