Lipid hydroperoxide generation, turnover, and effector action in biological systems.
Lipid hydroperoxide generation, turnover, and effector action in biological systems.
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发表时间：
1998-08
影响因子：
6.5
通讯作者：
A. Girotti
中科院分区：
文献类型：
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作者：
A. Girotti
脂质过氧化是细胞膜、脂蛋白和其他含脂质结构中氧化损伤的一个众所周知的例子。不饱和磷脂、糖脂和胆固醇的过氧化改性可在由以下物质触发的反应中发生：i）自由基物质，如衍生自铁介导的过氧化氢还原的氧自由基、过氧自由基和羟基自由基，或ii）非自由基物质，如由超氧化物与一氧化氮反应产生的单线态氧、臭氧和过氧亚硝酸根。脂质过氧化氢（LOOH）是脂质过氧化的重要非自由基中间体，其鉴定通常可以提供有价值的机制信息，例如，无论初级反应是由单线态氧还是氧自由基介导的。某些胆固醇衍生的氢过氧化物（ChOOH）在这方面已经非常有效地用于模型系统和细胞。由于比母体脂质极性更大，LOOH扰乱膜结构/功能，并且仅在此基础上就可能对细胞有害。然而，LOOH也可以参与氧化还原反应，其性质和程度通常决定了过氧化损伤是否加剧或预防。加重可能反映铁催化的单电子还原的LOOHs，导致自由基介导的链过氧化，而预防可能反映硒过氧化物酶催化的双电子还原的LOOHs相对无毒的醇。在氧化应激的细胞中，这两种途径之间的LOOH分配仍然知之甚少，但最近涉及各种ChOOH的细胞研究已经开始阐明这一重要问题。正在深入研究的相关兴趣的一个方面是脂质过氧化/LOOH介导的应激信号传导，这可能引起各种细胞反应，从诱导抗氧化酶到凋亡性死亡。对这些过程的持续探索将对我们理解与过氧化应激相关的疾病状态具有重要意义。
Lipid peroxidation is a well known example of oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures. Peroxidative modification of unsaturated phospholipids, glycolipids, and cholesterol can occur in reactions triggered by i) free radical species such as oxyl radicals, peroxyl radicals, and hydroxyl radicals derived from iron-mediated reduction of hydrogen peroxide or ii) non-radical species such as singlet oxygen, ozone, and peroxynitrite generated by the reaction of superoxide with nitric oxide. Lipid hydroperoxides (LOOHs) are prominent non-radical intermediates of lipid peroxidation whose identification can often provide valuable mechanistic information, e.g., whether a primary reaction is mediated by singlet oxygen or oxyradicals. Certain cholesterol-derived hydroperoxides (ChOOHs) have been used very effectively in this regard, both in model systems and cells. Being more polar than parent lipids, LOOHs perturb membrane structure/function and can be deleterious to cells on this basis alone. However, LOOHs can also participate in redox reactions, the nature and magnitude of which often determines whether peroxidative injury is exacerbated or prevented. Exacerbation may reflect iron-catalyzed one-electron reduction of LOOHs, resulting in free radical-mediated chain peroxidation, whereas prevention may reflect selenoperoxidase-catalyzed two-electron reduction of LOOHs to relatively non-toxic alcohols. LOOH partitioning between these two pathways in an oxidatively stressed cell is still poorly understood, but recent cell studies involving various ChOOHs have begun to shed light on this important question. An aspect of related interest that is under intensive investigation is lipid peroxidation/LOOH-mediated stress signaling, which may evoke a variety of cellular responses, ranging from induction of antioxidant enzymes to apoptotic death. Ongoing exploration of these processes will have important bearing on our understanding of disease states associated with peroxidative stress.