Autophagy
Autophagy
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DOI：
10.1007/978-3-030-21573-6_10048-1
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
H. Simon;R. Friis
中科院分区：
文献类型：
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作者：
H. Simon;R. Friis
抗氧化剂是一种以功能而非常见结构基序为特征的分子。它们的共同特征是在生物系统中发挥“抗”氧化剂的作用。由于组织暴露于高浓度的物理溶解的分子氧以及含氮生物分子，氧化剂（通常与抗氧化剂相反）是生物系统中产生的氧和/或氮衍生的活性物质（图1）。当然，还有大量其他生物学相关的活性物质和氧化剂，包括以硫为中心的自由基或氯化物质。因此，正如我们将在本条目中使用的那样，使用经常使用的缩写词 ROS（“活性氧”）来提及所有这些内容，严格来说是不正确的。然而，它的优点是避免了两个不一致之处：如果图 1 中所示的化合物被简单地称为“氧化剂”或“自由基”，则会忽略这样一个事实：并非所有这些化合物都必然是氧化剂（例如超氧阴离子，它可能在生物系统中充当还原剂）或自由基（例如非自由基活性物质 H2O2、ONOO À、 次氯酸）。 ROS 可能是内源性产生的，也可能是在暴露于外源刺激时产生的。内源生成发生在电子在有氧的情况下传递的地方，例如在线粒体呼吸链中或外源代谢过程中（Klotz 和 Steinbrenner 2017；Kehrer 和 Klotz 2015）。它可能由专用酶催化，包括还原氧生成超氧化物或过氧化氢的氧化酶，内源性 ROS 的生成可能是其他 ROS 相互作用的产物，例如过氧亚硝酸盐，它是通过超氧化物和一氧化氮自由基的组合产生的，或羟基自由基，它可能是由金属离子诱导产生的 减少过氧化物（芬顿反应）。引起内源性ROS产生的外源性刺激包括物理刺激，例如紫外线辐射或电离辐射和毒素。正如在化学上，ROS 不一定是氧化剂一样，相反的抗氧化剂也不一定在生物环境中充当还原剂：事实上，氧化剂可以引发适应性细胞反应，例如通过刺激转录因子，因此可以作为四种常见的抗氧化策略之一（Sies 1993；Klotz 2015）。这些策略包括（i）防止氧化剂形成，（ii）拦截氧化剂与其分子靶标之间的反应，（iii）修复被氧化剂损坏的分子，以及（iv）通过应激诱导的信号传导，通过上调内源性抗氧化防御来适应。
Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing to the exposure of tissues to high concentrations of physically dissolved molecular oxygen as well as to nitrogen-containing biomolecules, the oxidants, usually implied as being opposed by antioxidants, are oxygen-and/or nitrogen-derived reactive species generated in biological systems (Fig. 1). There is, of course, a plethora of other biologically relevant reactive species and oxidants, including sulfur-centered radicals or chlorinated species. Referring to all of these using the frequently employed acronym ROS (“reactive oxygen species”), as we will in this entry, is, therefore, strictly speaking, incorrect. It has, however, the advantage that two inconsistencies are being avoided: if the compounds shown in Fig. 1 were referred to simply as “oxidants” or “free radicals,” this would neglect the fact that not all of these compounds are necessarily oxidants (such as the superoxide anion, which may act as reductant in biological systems) or radicals (such as the non-radical reactive species H2O2, ONOO À, HOCl). ROS may be generated endogenously and upon exposure to exogenous stimuli. Endogenous generation occurs wherever electrons are passed along in the presence of oxygen, such as in the mitochondrial respiratory chain or during xenobiotic metabolism (Klotz and Steinbrenner 2017; Kehrer and Klotz 2015). It may be catalyzed by dedicated enzymes, including oxidases that reduce oxygen to generate superoxide or hydrogen peroxide, and endogenous generation of ROS may occur as (by) product of an interaction of other ROS–such as peroxynitrite, which is generated through a combination of superoxide and nitrogen monoxide radicals, or hydroxyl radical, which may be generated by a metal ion-induced reduction of peroxides (Fenton reaction). Exogenous stimuli eliciting the endogenous generation of ROS include physical stimuli such as UV radiation or ionizing radiation and toxins. Just as, chemically, ROS are not necessarily oxidants, the opposing antioxidants not necessarily act as reductants in a biological setting: in fact, oxidants can evoke an adaptive cellular response, for example, by stimulating transcription factors, and therefore serve one of the four commonly found antioxidative strategies (Sies 1993; Klotz 2015). These strategies include (i) the prevention of oxidant formation,(ii) interception of reactions between oxidants and their molecular targets,(iii) repair of molecules damaged by oxidants, and (iv) adaptation, through stress-induced signaling, by upregulating endogenous antioxidant defenses.