Protein, lipid and DNA repair systems in oxidative stress: the free-radical theory of aging revisited.
Protein, lipid and DNA repair systems in oxidative stress: the free-radical theory of aging revisited.
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DOI：
10.1159/000213257
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发表时间：
1991
期刊：
影响因子：
3.5
通讯作者：
Robert E. Pacifici;K. Davies
中科院分区：
文献类型：
--
作者：
Robert E. Pacifici;K. Davies
需氧生物体不断暴露于氧自由基和相关氧化剂。抗氧化剂化合物和酶，他们已经发展消除了大部分潜在的破坏性自由基/氧化剂;然而，损害细胞蛋白质，脂质，核酸和碳水化合物，甚至可以在正常的生理条件下观察到。细胞成分的再还原（直接修复）对某些生物分子可能很重要。然而，在迄今为止研究的大多数情况下，酶促降解（通过蛋白酶、脂肪酶、核酸酶）似乎释放受损的元素用于排泄，并保存未受损的组分用于再利用（间接修复）。此外，去除受损组分似乎可以防止或减少氧化大分子的潜在细胞毒性。几项研究已经报道了氧化损伤的细胞成分随着年龄的积累（例如，白内障形成、脂褐质）。这些报告证明氧化损伤是导致衰老过程的几个因素之一，并至少部分支持了衰老的自由基理论。然而，对抗氧化酶和抗氧化化合物的活性或水平与年龄相关的变化的研究尚未完全了解自由基/氧化剂在衰老过程中的假定作用。在这篇综述中，我们提出的假设，减少活动或组成水平的氧化修复酶可能会导致渐进积累的氧化损伤与老化。此外，对氧化应激（氧化应激基因和蛋白质的诱导）产生有效反应的能力可能会随着年龄的增长而下降，从而使老年细胞和生物体易受氧化损伤。
Aerobic organisms are constantly exposed to oxygen radicals and related oxidants. The antioxidant compounds and enzymes they have evolved remove most of the potentially damaging radicals/oxidants; however, damage to cellular proteins, lipids, nucleic acids and carbohydrates can be observed even under normal physiological conditions. Re-reduction of cellular components (direct repair) may be important for some biomolecules. In most cases studied to date, however, enzymatic degradation (by proteases, lipases, nucleases) appears to release damaged elements for excretion and conserve undamaged components for reutilization (indirect repair). In addition, the removal of damaged components appears to prevent or diminish the potential cytotoxicity of oxidized macromolecules. Several studies have reported an accumulation of oxidatively damaged cellular components with age (e.g., cataract formation, lipofuscin). Such reports are evidence that oxidant damage is one of several factors which contribute to the aging process, and provide at least partial support for the free-radical theory of aging. Studies of age-related changes in the activities, or levels of antioxidant enzymes and antioxidant compounds, however, have not provided complete understanding of the putative role of free radicals/oxidants in the aging process. In this review, we present the hypothesis that decreased activities or constitutive levels of oxidant repair enzymes may contribute to a progressive accumulation of oxidant damage with aging. Furthermore, the ability to mount an effective response to oxidative stress (induction of oxidant stress genes and proteins) may decline with age, thus predisposing older cells and organisms to oxidant damage.