鱼藤酮诱导线粒体轻度损伤细胞氧化应激时硫氧还蛋白转录水平降低  

Transcription of Thioredoxin was Inhibited in Rotenone-induced Mitochondrial Dysfunctional Cells Exposed to H_2O_2

作　　者：丁红群[1] 丁镇[1] 熊御云[2] 高静[2] 

机构地区：[1]南京大学生命科学学院,南京210093 [2]江苏大学药学院,镇江212013

出　　处：《细胞生物学杂志》2007年第5期753-757,共5页Chinese Journal of Cell Biology

基　　金：教育部优秀青年教师资助计划项目;江苏大学高级人才科研启动基金资助(No.07JDG012)~~

摘　　要：观察鱼藤酮诱导的线粒体轻度损伤细胞氧化应激时硫氧还蛋白转录水平的变化,探讨细胞氧化损伤的可能机制。通过荧光素发光法检测ATP生成、细胞内活性氧(ROS)水平的变化,流式细胞术检测线粒体膜电位,了解低剂量鱼藤酮对线粒体功能的影响;继而用H2O2诱导细胞氧化损伤,MTT法检测细胞活性,观察正常及线粒体缺陷细胞氧化应激时,胞内硫氧还蛋白(Trx)mRNA水平的变化。结果表明,鱼藤酮以剂量依赖方式抑制线粒体ATP的产生、降低线粒体膜电位,而细胞内ROS水平增高;当线粒体损伤细胞氧化应激时胞内Trx mRNA水平降低,提示鱼藤酮诱导线粒体轻度损伤细胞抗氧化能力降低与Trx转录受到抑制有关。To study the pathological changes of thioredoxin （Trx） mRNA in cells exposed to H2O2 with mild mitochondrial dysfunction, the human neuroblastoma SH-SY5Y cells were insulted by low dose of rotenone to mimic the partial complex I impairment in PD. On this in vitro model, the changes of ATP and reactive oxygen species （ROS） production, and mitochondrial membrane potential （MMP） were investigated to compare the differences between the mitochondrial deficiency cells and normal ones. Furthermore, mRNA of intracellular redox protein, thioredoxin （Trx）, from both kinds of cells followed by H2O2 exposure were analyzed. The results demonstrated that rotenone could dose dependently decrease cellular ATP level and MMP, increase cellular ROS production. Without affecting the cell viability, 3 nmol/L rotenone exposure do not alter the cell morphology and ATP synthesis but increased the ROS generation, which indicated mitochondria had been insulted slightly. It was found that Trx mRNA levels in mitochondrial dysfunctional SH-SY5Y cells insulted by H2O2 were lower than normal ones. These results, together with our previous study, demonstrated that the increased susceptibility to oxidative stress in mitochondrial dysfunctional SH-SY5Y cells might be at least in part related to the down-regulation of Trx.

关 键 词：帕金森病 线粒体缺陷 鱼藤酮 氧化应激 硫氧还蛋白 

分 类 号：R742.5[医药卫生—神经病学与精神病学]