Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine
Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine
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DOI：
10.1073/pnas.1804932115
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发表时间：
2018-06-05
影响因子：
11.1
通讯作者：
Radi, Rafael
中科院分区：
文献类型：
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作者：
Radi, Rafael
氧源自由基和相关氧化剂是好氧生物一生中普遍存在的短寿命中间体。这些活性物质参与氧化还原反应，导致生物分子的氧化修饰，其中蛋白质和脂质是首选目标。尽管哺乳动物细胞和微生物中存在广泛的酶促和非酶促抗氧化系统，但过量的氧化剂形成会导致新产物的积累，从而损害细胞功能和结构，导致细胞退化和死亡。氧化事件与病理状况和正常衰老过程有关。值得注意的是，生理水平的氧化剂也通过稳态氧化还原敏感的细胞信号级联来调节细胞功能。另一方面，一氧化氮(NO)- n中心点)是一种自由基和弱氧化剂，通过与血红素蛋白的可逆相互作用，代表了一种主要的生理调节剂。（NO）- n -中心点的生物利用度和作用受其与超氧自由基（O-2（中心点-））的快速反应调节，产生一种不寻常的活性过氧化物，过氧亚硝酸盐，代表氧自由基和(NO)- n -中心点途径的融合。在这篇开篇文章中，我总结了自由基生物化学早期和显著的发展，以及该领域后来向分子医学的发展；这一转变包括我们的贡献揭示了(NO)- n中心点与氧化还原中间体和代谢的关系。过氧亚硝酸盐的生化表征、鉴定和定量及其在疾病过程中的作用已经引起了我们的广泛关注。作为蛋白质氧化和硝化、脂质过氧化、线粒体功能障碍和细胞死亡的媒介，过氧亚硝酸盐既是一种病理生理相关的内源性细胞毒素，也是一种对抗入侵病原体的细胞毒性效应物。
Oxygen-derived free radicals and related oxidants are ubiquitous and short-lived intermediates formed in aerobic organisms throughout life. These reactive species participate in redox reactions leading to oxidative modifications in biomolecules, among which proteins and lipids are preferential targets. Despite a broad array of enzymatic and nonenzymatic antioxidant systems inmammalian cells andmicrobes, excess oxidant formation causes accumulation of new products that may compromise cell function and structure leading to cell degeneration and death. Oxidative events are associated with pathological conditions and the process of normal aging. Notably, physiological levels of oxidants also modulate cellular functions via homeostatic redox-sensitive cell signalingcascades. On the other hand, nitric oxide ((NO)-N-center dot), a free radical and weak oxidant, represents a master physiological regulator via reversible interactions with heme proteins. The bioavailability and actions of (NO)-N-center dot are modulated by its fast reaction with superoxide radical (O-2(center dot-)), which yields an unusual and reactive peroxide, peroxynitrite, representing themerging of the oxygen radicals and (NO)-N-center dot pathways. In this Inaugural Article, I summarize early and remarkable developments in free radical biochemistry and the later evolution of the field toward molecularmedicine; this transition includes our contributions disclosing the relationship of (NO)-N-center dot with redox intermediates andmetabolism. The biochemical characterization, identification, and quantitation of peroxynitrite and its role in disease processes have concentratedmuch of our attention. Being amediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens.