Departamento de Bioquímica, Facultad de Medicina, and Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay.
Physiol Rev. 2022 Oct 1;102(4):1881-1906. doi: 10.1152/physrev.00005.2022. Epub 2022 May 23.
The free radical nitric oxide (NO) is a key mediator in different physiological processes such as vasodilation, neurotransmission, inflammation, and cellular immune responses, and thus preserving its bioavailability is essential. In several disease conditions, superoxide radical (O) production increases and leads to the rapid "inactivation" of NO by a diffusion-controlled radical termination reaction that yields a potent and short-lived oxidant, peroxynitrite. This reaction not only limits NO bioavailability for physiological signal transduction but also can divert and switch the biochemistry of NO toward nitrooxidative processes. Indeed, since the early 1990s peroxynitrite (and its secondary derived species) has been linked to the establishment and progression of different acute and chronic human diseases and also to the normal aging process. Here, we revisit an earlier and classical review on the role of peroxynitrite in human physiology and pathology (Pacher P, Beckman J, Liaudet L. 87: 315-424, 2007) and further integrate, update, and interpret the accumulated evidence over 30 years of research. Innovative tools and approaches for the detection, quantitation, and sub- or extracellular mapping of peroxynitrite and its secondary products (e.g., protein 3-nitrotyrosine) have allowed us to unambiguously connect the complex biochemistry of peroxynitrite with numerous biological outcomes at the physiological and pathological levels. Furthermore, our current knowledge of the NO/O and peroxynitrite interplay at the cell, tissue, and organ levels is assisting in the discovery of therapeutic interventions for a variety of human diseases.
自由基一氧化氮（NO）是多种生理过程的关键介质，如血管舒张、神经递质传递、炎症和细胞免疫反应，因此保持其生物利用度至关重要。在几种疾病状态下，超氧自由基（O）的产生增加，并导致通过扩散控制的自由基终止反应迅速“失活”NO，生成一种强效且短暂的氧化剂过氧亚硝酸根。该反应不仅限制了 NO 用于生理信号转导的生物利用度，而且还可以改变和转换 NO 的生物化学途径，使其向硝基氧化过程转移。事实上，自 20 世纪 90 年代初以来，过氧亚硝酸根（及其次级衍生物种）已与多种急性和慢性人类疾病的发生和发展以及正常衰老过程相关联。在这里，我们重新回顾了早期一篇关于过氧亚硝酸根在人类生理学和病理学中作用的经典综述（Pacher P, Beckman J, Liaudet L. 87: 315-424, 2007），并进一步整合、更新和解释了 30 多年来的研究积累的证据。用于检测、定量和亚细胞或细胞外定位过氧亚硝酸根及其次级产物（如蛋白质 3-硝基酪氨酸）的创新工具和方法，使我们能够明确地将过氧亚硝酸根的复杂生物化学与生理和病理水平的众多生物学结果联系起来。此外，我们目前对细胞、组织和器官水平上的 NO/O 和过氧亚硝酸根相互作用的认识，正在协助发现各种人类疾病的治疗干预措施。
