Mitochondria-derived reactive oxygen species mediate sympathoexcitation induced by angiotensin II in the rostral ventrolateral medulla
Mitochondria-derived reactive oxygen species mediate sympathoexcitation induced by angiotensin II in the rostral ventrolateral medulla
复制标题
DOI：
10.1097/hjh.0b013e32830dd5d3
复制
发表时间：
2008-11-01
影响因子：
4.9
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Nozoe, Masatsugu;Hirooka, Yoshitaka;Sunagawa, Kenji
目的中枢神经系统中的活性氧（Reactive oxygen species，ROS）被认为参与了心血管疾病如高血压、心力衰竭等的交感神经兴奋。烟酰胺腺嘌呤二核苷酸磷酸氧化酶是中枢神经系统中ROS的主要来源，其充当血管紧张素II（AngII）的关键介质（介质）。目前尚不清楚，但是，是否线粒体衍生的活性氧在中枢神经系统中也参与在symposiumexcitation.Methods在体内研究中，我们调查是否血管紧张素II引起的升压反应，在头端腹外侧延髓，控制交感神经活动，是由腺病毒介导的基因转移的线粒体衍生的抗氧化剂（锰-SOD）衰减。在体外研究中，使用分化的PC-12细胞与交感神经元的特性相似，我们研究是否血管紧张素II增加线粒体ROS production.Results过表达的锰-SOD衰减血管紧张素II诱导的升压反应，也抑制血管紧张素II诱导的ROS的生产，在延髓头端腹外侧微透析评估。使用还原的MitoTracker red，我们表明AngII增加体外分化的PC-12细胞中线粒体ROS的产生。Mn-SOD和鱼藤酮，线粒体呼吸复合物I抑制剂，过表达抑制血管紧张素II诱导的活性氧产生。用乙二醇双-N，N '，N'-四乙酸酯（EGTA）和对三氟甲氧羰基氰苯腙（p-trifluoromethoxycarbonylcyanide phenylhydrazone，p-trifluoromethoxycarbonylcyanone，p-phenylhydrazone，p-trifluoromethoxycarbonylcyanide）处理线粒体，可阻断Ang Ⅱ诱导的线粒体ROS产生。J Hypertens 26：2176-2184（c）2008年Wolters Kluwer Health垂直杆Lippincott威廉姆斯& Wilkins。
Objectives Reactive oxygen species (ROS) in the central nervous system are thought to contribute to sympathoexcitation in cardiovascular diseases such as hypertension and heart failure. Nicotinamide adenine dinucleotide phosphate oxidase is a major source of ROS in the central nervous system, which acts as a key mediator (mediators) of angiotensin II (AngII). It is not clear, however, whether mitochondria- derived ROS in the central nervous system also participate in sympathoexcitation.Methods In an in-vivo study, we investigated whether the AngII-elicited pressor response in the rostral ventrolateral medulla, which controls sympathetic nerve activity, is attenuated by adenovirus-mediated gene transfer of a mitochondria- derived antioxidant (Mn-SOD). In an in-vitro study, using differentiated PC-12 cells with characteristics similar to those of sympathetic neurons, we examined whether AngII increases mitochondrial ROS production.Results Overexpression of Mn-SOD attenuated the AngII-induced pressor response and also suppressed AngII-induced ROS production, as evaluated by microdialysis in the rostral ventrolateral medulla. Using reduced MitoTracker red, we showed that AngII increased mitochondrial ROS production in differentiated PC-12 cells in vitro. Overexpression of Mn-SOD and rotenone, a mitochondrial respiratory complex I inhibitor, suppressed AngII-induced ROS production. Depletion of extracellular Ca2+ with ethylene glycol bis-N, N, N', N'-tetraacetate (EGTA) and administration of p-trifluoromethoxycarbonylcyanide phenylhydrazone, which prevents further Ca2+ uptake into the mitochondria, blocked AngII-elicited mitochondrial ROS production.Conclusion These results indicate that AngII increases the intracellular Ca2+ concentration and that the increase in mitochondrial Ca2+ uptake leads to mitochondrial ROS production. J Hypertens 26: 2176-2184 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.