Mechanisms of cell injury by activated oxygen species.
Mechanisms of cell injury by activated oxygen species.
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DOI：
10.1289/ehp.94102s1017
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发表时间：
1994-12
影响因子：
10.4
通讯作者：
Farber JL
中科院分区：
文献类型：
--
作者：
Farber JL
目前的证据表明，O2-和H2 O2伤害细胞作为一个更强大的氧化物种的产生的结果。除了O2-和H2 O2之外，介导致死性细胞损伤的复合物的第三个必需组分是三价铁的细胞来源。与所有可用数据最一致的假设表明，O2-将三价铁的细胞来源还原为亚铁，然后后者与H2 O2反应产生更有效的氧化物质，如.OH或同等活性物质。反过来，.OH引发细胞膜磷脂的过氧化分解。OH也会损害线粒体内膜。在线粒体脱髓鞘后，启动一系列事件，其类似地导致细胞活力丧失。DNA代表. OH的第三个细胞靶点。根据细胞类型，氧化性DNA损伤可以通过与聚（ADP-核糖）聚合酶的活化相关的机制与细胞杀伤偶联。
Current evidence suggests that O2- and H2O2 injure cells as a result of the generation of a more potent oxidizing species. In addition to O2- and H2O2, the third essential component of the complex that mediates the lethal cell injury is a cellular source of ferric iron. The hypothesis most consistent with all the available data suggests that O2- reduces a cellular source of ferric to ferrous iron, and the latter then reacts with H2O2 to produce a more potent oxidizing species, like the .OH or an equivalently reactive species. In turn, .OH initiates the peroxidative decomposition of the phospholipids of cellular membranes. .OH also damages the inner mitochondrial membrane. Upon mitochondrial deenergization, a sequence of events is initiated that similarly leads to the loss of viability of the cell. DNA represents a third cellular target of .OH. Depending on the cell type, oxidative DNA damage can be coupled to cell killing through a mechanism related to the activation of poly (ADP-ribose) polymerase.