Girotti A W
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226-4801, USA.
J Lipid Res. 1998 Aug;39(8):1529-42.
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.
脂质过氧化是细胞膜、脂蛋白及其他含脂结构中氧化损伤的一个著名例子。不饱和磷脂、糖脂和胆固醇的过氧化修饰可发生在以下反应中：i）自由基物种引发的反应，如由铁介导的过氧化氢还原产生的氧自由基、过氧自由基和羟基自由基；ii）非自由基物种引发的反应，如超氧化物与一氧化氮反应生成的单线态氧、臭氧和过氧亚硝酸盐。脂质氢过氧化物（LOOHs）是脂质过氧化的主要非自由基中间体，其鉴定通常能提供有价值的机制信息，例如，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（ChOOHs）在这方面已在模型系统和细胞中得到非常有效的应用。由于LOOHs比母体脂质极性更强，它们会扰乱膜结构/功能，仅基于这一点就可能对细胞有害。然而，LOOHs也可参与氧化还原反应，其性质和程度往往决定了过氧化损伤是加剧还是得到预防。损伤加剧可能反映了铁催化的LOOHs单电子还原，导致自由基介导的链式过氧化，而预防可能反映了硒过氧化物酶催化的LOOHs双电子还原为相对无毒的醇。氧化应激细胞中这两条途径之间的LOOH分配仍知之甚少，但最近涉及各种ChOOHs的细胞研究已开始阐明这个重要问题。正在深入研究的一个相关有趣方面是脂质过氧化/LOOH介导的应激信号传导，它可能引发多种细胞反应，从诱导抗氧化酶到凋亡死亡。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。
