Mitochondria-targeted redox probes as tools in the study of oxidative damage and ageing

Mitochondria-targeted redox probes as tools in the study of oxidative damage and ageing
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DOI:
10.1016/j.mad.2005.03.026
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发表时间:
2005-09-01
影响因子:
5.3
通讯作者:
Murphy, MP
Murphy, MP
中科院分区:
医学3区
文献类型:
--
作者:
James, AM;Cochemé, HM;Murphy, MP

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线粒体活性氧(ROS)和氧化损伤与一系列年龄相关的人类病理学相关。线粒体ROS的产生也可能是应激反应和信号转导途径中的一个因素。然而,目前用于测量和影响体内线粒体ROS产生的方法往往缺乏所需的特异性。为了帮助阐明线粒体ROS产生在衰老中的潜在作用,我们开发了一系列可能在体内有用的靶向ROS探针。这是通过将亲脂性阳离子共价连接到ROS反应性部分,导致其在线粒体内的膜电位依赖性积累来实现的。迄今为止开发的线粒体靶向分子包括使线粒体ROS解毒的抗氧化剂、与线粒体ROS反应的探针以及特异性标记线粒体蛋白硫醇的试剂。在这里,我们概述了如何形成和线粒体ROS生产的后果可以使用这些探针进行调查。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Mitochondrial reactive oxygen species (ROS) and oxidative damage are associated with a range of age-related human pathologies. It is also likely that mitochondrial ROS generation is a factor in stress response and signal transduction pathways. However, current methods for measuring and influencing mitochondrial ROS production in vivo often lack the desired specificity. To help elucidate the potential role of mitochondrial ROS production in ageing, we have developed a range of mitochondria-targeted ROS probes that may be useful in vivo. This was achieved by covalently attaching a lipophilic cation to a ROS-reactive moiety causing its membrane potential-dependent accumulation within mitochondria. Mitochondria-targeted molecules developed so far include antioxidants that detoxify mitochondrial ROS, probes that react with mitochondrial ROS, and reagents that specifically label mitochondrial protein thiols. Here, we outline how the formation and consequences of mitochondrial ROS production can be investigated using these probes. (c) 2005 Elsevier Ireland Ltd. All rights reserved.