目的探讨金属硫蛋白(metallothionein,MT)和线粒体解偶联蛋白3(uncoupling protein 3,UCP3)抗阿霉素(doxorubicin,Dox)心脏毒性的作用及具体分子机制。方法体内实验以MT敲除型(MT^(-/-))小鼠和MT野生型(MT^(+/+))小鼠为动物模型并通过...目的探讨金属硫蛋白(metallothionein,MT)和线粒体解偶联蛋白3(uncoupling protein 3,UCP3)抗阿霉素(doxorubicin,Dox)心脏毒性的作用及具体分子机制。方法体内实验以MT敲除型(MT^(-/-))小鼠和MT野生型(MT^(+/+))小鼠为动物模型并通过腹腔注射给予Dox(15 mg/kg·bw);体外实验采用出生1~3 d的两种小鼠的心脏构建心肌细胞体外原代培养模型,并给于Dox(1μmol/L)和NAC(5 mmol/L)处理。通过苏木素-伊红(HE)染色法检测Dox对小鼠心脏组织的损伤作用;免疫组织化学染色法检测MT的表达水平;细胞色素C还原测定法检测O_(2)^(-)的含量;TBARS法测定MDA的含量;RT-qPCR试验方法检测UCP3基因表达水平;Western blot方法检测UCP3蛋白表达水平;免疫共沉淀方法检测MT与UCP3的相互作用方式。结果Dox可导致心脏组织病理学改变,氧化损伤,超氧阴离子产生增多,抑制UCP3基因和蛋白表达(P<0.05,P<0.01),但是MT并不能通过与UCP3直接结合而发挥作用。NAC可抑制Dox导致的两种心肌细胞中UCP3基因表达水平的下降(P<0.05),但是对UCP3蛋白表达水平的下降没有抑制作用。结论MT除了可通过清除氧自由基抵抗Dox对UCP3基因表达的抑制作用外还可通过其他途径调控UCP3的蛋白表达水平。展开更多
Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercis...Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.展开更多
基金supported by grants from National Basic ResearchProgram of China (2006CB503910, 2006CB806506, 2006CB911001)The National Natural Science Foundation of China (30721003)~~
基金supported by research grants from the National Natural Science Foundation of China(No.31110103919, 31200894,31000523,30771048,30470837,31071040,and 30270638)Tianjin Municipal Sci-tech-innovation Base Project (No.10SYSYJC28400)+1 种基金Tianjin Science and Technology Planning Project(No.12JCQNJC07900)General Administration of Sport of China Basic Project(No.10B058)
文摘Mitochondrial redox metabolism has long been recognized as being central to the effects of aging and the development of age-related pathologies in the major oxidative organs. Consistent evidence has shown that exercise is able to retard the onset and impede the progression of aging by modifying mitochondrial oxidant--antioxidant homeostasis. Here we provide a broad overview of the research evidence showing the relationship between mitochondrial redox metabolism, aging and exercise. We address part aspects of mitochondrial reactive oxygen species （ROS） metabolism, from superoxide production to ROS detoxification, especially antioxidant enzymes and uncoupling protein. Furthermore, we describe mitochondrial remodeling response to aging and exercise, which is accompanied by bioenergetics and redox regulation. In addition, potential mechanisms for redox signaling involved in mitochondrial remodeling and redox metabolism regulation are also reviewed.
