Therapeutics against mitochondrial oxidative stress in animal models of aging
Therapeutics against mitochondrial oxidative stress in animal models of aging
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DOI：
10.1111/j.1749-6632.2002.tb02104.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Melov, S
中科院分区：
文献类型：
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作者：
Melov, S
在正常新陈代谢过程中，在线粒体呼吸链内产生活性氧物种(ROS)。这些ROS具有氧化和破坏各种细胞成分的能力，包括脂质、DNA和蛋白质。我们已经采取了遗传学和药理学的方法来描述线粒体ROS可以氧化损伤的分子靶点的范围。具体地说，我们使用缺乏线粒体形式的超氧化物歧化酶的小鼠(超氧化物歧化酶2(-/-)小鼠)来更好地了解线粒体氧化应激可能产生的表型。SOD2(-/-)小鼠可以用来测试抗氧化剂的效果，更广泛地说，抗氧化剂对抗线粒体氧化应激的效果。我们在线粒体氧化应激的哺乳动物模型中评估了超氧化物歧化酶/过氧化氢酶模拟物，并显示出高度的保护线粒体内产生的ROS的有效性。同样，我们使用线虫秀丽线虫来测试有效的抗氧化剂疗法可以延长无脊椎动物寿命的假设。
During the course of normal metabolism, reactive oxygen species (ROS) are produced from within the respiratory chain of the mitochondria. These ROS have the capacity to oxidize and damage a variety of cellular constituents including lipids, DNA, and proteins. We have taken a genetic and pharmacological approach in delineating the range of molecular targets that can be oxidatively damaged by mitochondrial ROS. Specifically, we use mice that are lacking the mitochondrial form of superoxide dismutase (sod 2(-/-) mice) to better understand the possible phenotypes that can arise from mitochondrial oxidative stress. sod 2(-/-) mice can be used to test the efficacy of antioxidants, and more generally the efficacy of antioxidants against mitochondrial oxidative stress. We have evaluated superoxide dismutase/catalase mimetics in this mammalian model of mitochondrial oxidative stress, and have shown a high degree of efficacy in protecting against ROS produced within the mitochondria. Similarly, we have employed the nematode Caenorhabditis elegans to test the hypothesis that effective antioxidant therapy can prolong the life span of an invertebrate.