Isoprostane generation and function.
Isoprostane generation and function.
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DOI：
10.1021/cr200160h
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发表时间：
2011-10-12
期刊：
影响因子：
62.1
通讯作者：
Roberts, L. Jackson, II
中科院分区：
文献类型：
--
作者：
Milne, Ginger L.;Yin, Huiyong;Hardy, Klarissa D.;Davies, Sean S.;Roberts, L. Jackson, II
主要来源于分子氧的自由基与多种人类疾病有关，包括动脉粥样硬化、癌症、神经退行性疾病和衰老。1自由基对组织生物分子（包括脂质、蛋白质和DNA）的损伤被认为对氧化应激的病理生理学有重要贡献。脂质容易受到自由基的攻击，导致形成许多过氧化产物。2异前列腺素（IsoPs）是一系列独特的类前列腺素化合物，通过花生四烯酸（一种普遍存在的多不饱和脂肪酸（PUFA））的非酶自由基引发的过氧化作用在体内形成。自从20多年前Morrow，Roberts和同事发现这些分子以来，一类IsoPs（F2-IsoPs）已成为评估内源性氧化应激的首选生物标志物，因为这些分子化学稳定，并且已在所有生物体液和组织中检测到。除了F2-IsoP之外，已经鉴定了具有不同环结构的多种IsoP。这些化合物中有几种具有有效的生物活性，可以解释氧化损伤的一些病理生理效应。此外，IsoP样分子也由许多不同的PUFA产生，包括R-亚麻酸、二十碳五烯酸（EPA）、肾上腺酸和二十二碳六烯酸（DHA）（图1）。文献中有许多优秀的综述，不仅描述了F2-IsoPs在人类健康和疾病中的定量，而且描述了这些分子的生物活性。因此，本综述旨在为读者提供我们目前关于IsoPs的知识的全面，最新的概述，包括其形成和代谢的化学和生物化学，测量这些化合物作为体内氧化应激标志物的实用性，以及它们的生物学特性。活性氧和氧化应激自由基是在其外轨道中含有一个或多个不成对电子的活性化学物质。活性氧（ROS）是一个术语，用于描述化学反应性，含氧分子，包括氧中心的自由基以及氧离子和过氧化物。在生命系统中产生的最常见的ROS是超氧阴离子（O2·OH）、过氧化氢（H2 O2）、羟基自由基（3 OH）、烷氧基自由基（RO 3）、过氧基（ROO 3）、单线态氧（1 O2）、14和臭氧。细胞中形成的其他相关活性物质包括过氧亚硝酸盐（ONOO）、一氧化氮（3 NO）、次氯酸（HOCl）和其他碳中心自由基。体内产生的ROS来源于内源性和外源性。ROS在有氧代谢过程中通过细胞中的还原-氧化（redox）反应不断产生。细胞内的线粒体是内源性ROS的主要来源。线粒体电子传递链（ETC）是线粒体的电子传递链。
Free radicals derived primarily from molecular oxygen have been implicated in a variety of human disorders including atherosclerosis, cancer, neurodegenerative diseases, and aging. 1 Damage to tissue biomolecules, including lipids, proteins, and DNA, by free radicals is postulated to contribute importantly to the pathophysiology of oxidative stress. Lipids are readily attacked by free radicals, resulting in the formation of a number of peroxidation products. 2 The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via the nonenzymatic free radical-initiated peroxidation of arachidonic acid, a ubiquitous polyunsaturated fatty acid (PUFA). Since discovery of these molecules over 20 years ago by Morrow, Roberts, and co-workers, one class of IsoPs, the F2-IsoPs, has become the biomarker of choice for assessing endogenous oxidative stress because these molecules are chemically stable and have been detected in all biological fluids and tissues analyzed. 3À5 In addition to F2-IsoPs, a variety of IsoPs with different ring structures have been identified. Several of these compounds possess potent biological activities that could account for some of the pathophysiological effects of oxidative injury. Further, IsoP-like molecules are also generated from a number of different PUFAs including R-linolenic acid, eicosapentaenoic acid (EPA), adrenic acid, and docosahexaenoic acid (DHA)(Figure 1). There are many excellent reviews in the literature describing not only the quantification of F2-IsoPs in human health and disease but also the biological activities of these molecules. 6À9 Thus, this review seeks to give readers a comprehensive, up-to-date overview of our current knowledge regarding IsoPs including the chemistry and biochemistry of their formation and metabolism, the utility of measuring these compounds as markers of in vivo oxidant stress, and their biological properties.1.1. Reactive Oxygen Species and Oxidative Stress Free radicals are reactive chemical species containing one or more unpaired electrons in their outer orbitals. Reactive oxygen species (ROS) is a term used to describe chemically reactive, oxygen-containing molecules including oxygen-centered free radicals as well as oxygen ions and peroxides. 10À13 The most common ROS generated in living systems are superoxide anion (O2• À), hydrogen peroxide (H2O2), hydroxyl radical (3 OH), alkoxyl radicals (RO3), peroxyl radicals (ROO3), singlet oxygen (1O2), 14 and ozone. 15 Other related reactive species formed in cells include peroxynitrite (ONOO À), nitric oxide (3NO), hypochlorous acid (HOCl), and other carbon-centered radicals. ROS generated in vivo are derived from both endogenous and exogenous sources. ROS are continuously generated during aerobic metabolism through reductionÀoxidation (redox) reactions in the cell. The mitochondria within a cell are a major source of endogenous ROS. The mitochondrial electron-transport chain (ETC) is the
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影响因子：
15.9
作者：
Bell-Parikh, LC;Ide, T;FitzGerald, GA
通讯作者：
FitzGerald, GA
影响因子：
4.8
作者：
Brooks, Joshua D.;Milne, Ginger L.;Morrow, Jason D.
通讯作者：
Morrow, Jason D.
影响因子：
7.1
作者：
BANG, HO;DYERBERG, J;SINCLAIR, HM
通讯作者：
SINCLAIR, HM
影响因子：
4.8
作者：
Bernoud-Hubac, N;Davies, SS;Roberts, LJ
通讯作者：
Roberts, LJ
影响因子：
4.8
作者：
Brame, CJ;Boutaud, O;Roberts, LJ
通讯作者：
Roberts, LJ