Kelso Geoffrey F, Porteous Carolyn M, Hughes Gillian, Ledgerwood Elizabeth C, Gane Alison M, Smith Robin A J, Murphy Michael P
Department of Chemistry, University of Otago, Box 56, Dunedin, New Zealand.
Ann N Y Acad Sci. 2002 Apr;959:263-74. doi: 10.1111/j.1749-6632.2002.tb02098.x.
Mitochondrial-targeted antioxidants that selectively block mitochondrial oxidative damage and prevent some types of cell death have been developed. These antioxidants are ubiquinone and tocopherol derivatives and are targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation. Because of the large mitochondrial membrane potential, these cations accumulated within mitochondria inside cells, where the antioxidant moiety prevents lipid peroxidation and protects mitochondria from oxidative damage. The mitochondrially localized ubiquinone also protected mammalian cells from hydrogen peroxide-induced apoptosis while an untargeted ubiquinone analogue was ineffective against apoptosis. When fed to mice these compounds accumulated within the brain, heart, and liver; therefore, using these mitochondrial-targeted antioxidants may help investigations of the role of mitochondrial oxidative damage in animal models of aging.
已经开发出了能够选择性阻断线粒体氧化损伤并防止某些类型细胞死亡的线粒体靶向抗氧化剂。这些抗氧化剂是泛醌和生育酚衍生物，通过与亲脂性三苯基鏻阳离子共价连接而靶向线粒体。由于线粒体内膜电位较大，这些阳离子在细胞内的线粒体内积累，在那里抗氧化部分可防止脂质过氧化并保护线粒体免受氧化损伤。线粒体定位的泛醌还能保护哺乳动物细胞免受过氧化氢诱导的凋亡，而未靶向的泛醌类似物对凋亡无效。当给小鼠喂食这些化合物时，它们会在脑、心脏和肝脏中积累；因此，使用这些线粒体靶向抗氧化剂可能有助于研究线粒体氧化损伤在衰老动物模型中的作用。
