Trostchansky Andrés, Rubbo Homero
Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Avda. General Flores 2125, Universidad de la República, Montevideo 11800, Uruguay.
Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Avda. General Flores 2125, Universidad de la República, Montevideo 11800, Uruguay.
Arch Biochem Biophys. 2017 Mar 1;617:155-161. doi: 10.1016/j.abb.2016.10.003. Epub 2016 Oct 5.
Nitrated derivatives of unsaturated fatty acids (nitro-fatty acids) are being formed and detected in human plasma, cell membranes and tissue, triggering signaling cascades via covalent and reversible post-translational modifications of nucleophilic amino acids in transcriptional regulatory proteins. Arachidonic acid (AA) represents a precursor of potent signaling molecules, i.e., prostaglandins and thromboxanes through enzymatic and non-enzymatic oxidative pathways. Arachidonic acid can be nitrated by reactive nitrogen species leading to the formation of nitro-arachidonic acid (NO-AA). A critical issue is the influence of NO-AA on prostaglandin endoperoxide H synthases, modulating inflammatory processes through redirection of AA metabolism and signaling. In this prospective article, we describe the key chemical and biochemical actions of NO-AA in vascular and astrocytes. This includes the ability of NO-AA to mediate unique redox signaling anti-inflammatory actions along with its therapeutic potential.
不饱和脂肪酸的硝化衍生物（硝基脂肪酸）正在人体血浆、细胞膜和组织中形成并被检测到，它们通过转录调节蛋白中亲核氨基酸的共价和可逆翻译后修饰触发信号级联反应。花生四烯酸（AA）是强效信号分子（即前列腺素和血栓素）通过酶促和非酶促氧化途径的前体。花生四烯酸可被活性氮物质硝化，导致形成硝基花生四烯酸（NO-AA）。一个关键问题是NO-AA对前列腺素内过氧化物H合酶的影响，它通过重新定向AA代谢和信号传导来调节炎症过程。在这篇前瞻性文章中，我们描述了NO-AA在血管和星形胶质细胞中的关键化学和生化作用。这包括NO-AA介导独特的氧化还原信号抗炎作用的能力及其治疗潜力。
