Melov Simon
Buck Institute for Age Research, Novato, California 94945, USA.
Ann N Y Acad Sci. 2002 Apr;959:330-40. doi: 10.1111/j.1749-6632.2002.tb02104.x.
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.
在正常新陈代谢过程中，线粒体呼吸链会产生活性氧（ROS）。这些ROS能够氧化并损伤多种细胞成分，包括脂质、DNA和蛋白质。我们采用遗传学和药理学方法来确定可被线粒体ROS氧化损伤的分子靶点范围。具体而言，我们使用缺乏线粒体形式超氧化物歧化酶的小鼠（sod 2(-/-)小鼠），以更好地了解线粒体氧化应激可能产生的表型。sod 2(-/-)小鼠可用于测试抗氧化剂的功效，更广泛地说，可用于测试抗氧化剂对抗线粒体氧化应激的功效。我们已在这种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，并证明其在保护免受线粒体内产生的ROS方面具有高度功效。同样，我们利用线虫秀丽隐杆线虫来检验有效抗氧化治疗可延长无脊椎动物寿命这一假设。
