Aging and the role of reactive nitrogen species
Aging and the role of reactive nitrogen species
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DOI：
10.1111/j.1749-6632.2002.tb02084.x
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Leeuwenburgh, C
中科院分区：
文献类型：
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作者：
Drew, B;Leeuwenburgh, C
自Denham Harman博士首次提出“衰老的自由基理论”以来，活性氧的作用及其对衰老的影响在过去的47年中受到了相当大的关注。“虽然由于涉及的途径数量无法计算而尚未完全理解，但有助于理解活性自由基对脂质，蛋白质和DNA氧化应激的潜在影响及其对衰老过程的贡献的手稿数量几乎每年呈指数级增长。最近，活性氮物质，如一氧化氮及其副产物硝酸盐（NO3-），亚硝酸盐（NO2-），过氧亚硝酸盐（ONOO-）和3-硝基酪氨酸的作用已被证明在细胞信号传导，血管舒张和免疫反应中具有直接作用。一氧化氮是由一组称为一氧化氮合酶的酶在细胞内产生的。目前，一氧化氮合酶有三种不同的亚型：神经元型（nNOS或NOS-1）、诱导型（iNOS或NOS-2）和内皮型（eNOS或NOS-3），以及几种亚型。而一氧化氮（NO.）是一种相对不反应的自由基，它能够形成其他反应中间体，这可能对蛋白质功能和整个生物体的功能产生影响。这些活性中间体可引发生物分子的亚硝化损伤，这反过来又可能导致与年龄相关的疾病，这是由于蛋白质的结构改变、酶活性的抑制和调节功能的干扰。本文将批判性地回顾硝化的证据和它在老化中所起的重要作用。此外，它将总结硝化的生理作用以及导致生物组织中硝化蛋白质的蛋白水解降解的机制。
The role of reactive oxygen species and its effects on aging has received considerable attention in the past 47 years since Dr. Denham Harman first proposed the "free radical theory of aging." Though not completely understood due to the incalculable number of pathways involved, the number of manuscripts that facilitate the understanding of the underlying effects of reactive radical species on the oxidative stress on lipids, proteins, and DNA and its contribution to the aging process increases nearly exponentially each year. More recently, the role of reactive nitrogen species, such as nitric oxide and its by-products nitrate (NO3-), nitrite (NO2-), peroxynitrite (ONOO-), and 3-nitrotyrosine have been shown to have a direct role in cellular signaling, vasodilation, and immune response. Nitric oxide is produced within cells by the actions of a group of enzymes called nitric oxide synthases. Presently, there are three distinct isoforms of nitric oxide synthase: neuronal (nNOS or NOS-1), inducible (iNOS or NOS-2), and endothelial (eNOS or NOS-3), and several subtypes. While nitric oxide (NO.) is a relative unreactive radical, it is able to form other reactive intermediates, which could have an effect on protein function and on the function of the entire organism. These reactive intermediates can trigger nitrosative damage on biomolecules, which in turn may lead to age-related diseases due to structural alteration of proteins, inhibition of enzymatic activity, and interferences of the regulatory function. This paper will critically review the evidence of nitration and the important role it plays with aging. Furthermore, it will summarize the physiological role of nitration as well as the mechanisms leading to proteolytic degradation of nitrated proteins within biological tissues.