Upstream Bioprocessing Group, National Institute for Bioprocessing Research and Training, NICB, Dublin City University, Dublin, Ireland.
Mass Spectrom Rev. 2011 Jan-Feb;30(1):121-41. doi: 10.1002/mas.20270.
Kidneys are the mammalian organs with widest range of oxidative status ranging from the well-perfused cortex to the relatively anoxic medulla. This organ is of key interest from the perspective of hypertension, an important contributor to human mortality, and there has been growing use of the spontaneously hypertensive rat (SHR) as a model to explore oxidative stress in hypertensive kidney. Nitrosative stress is often associated with oxidative stress and, like oxidative stress, can lead to covalent modification of protein side-chains. It is especially relevant to kidney because of high levels of both nitrite/nitrate and nitric oxide synthase in medulla. Because of their relatively low abundance and their well-known role in signal transduction, nitration of tyrosines to 3-nitrotyrosines (3NT) is of particular interest in this regard. This modification has the potential to contribute to changes in regulation, in protein activity and may provide a means of specific targeting of key proteins. Mass spectrometry (MS) offers a promising route to detecting this modification. This review surveys protein nitration in kidney disease and highlights opportunities for MS detection of nitrated residues in the SHR.
肾脏是哺乳动物器官中氧化状态范围最广的器官，从灌注良好的皮质到相对缺氧的髓质。从高血压的角度来看，这种器官是一个关键的关注点，高血压是导致人类死亡率的一个重要因素，人们越来越多地使用自发性高血压大鼠（SHR）作为一种模型来探索高血压肾脏中的氧化应激。硝化应激通常与氧化应激有关，并且与氧化应激一样，会导致蛋白质侧链的共价修饰。由于髓质中含有高浓度的亚硝酸盐/硝酸盐和一氧化氮合酶，因此硝化应激对肾脏特别重要。由于其相对丰度较低，以及它们在信号转导中的众所周知的作用，酪氨酸的硝化作用生成 3-硝基酪氨酸（3NT）在这方面特别有趣。这种修饰有可能导致调节、蛋白质活性的变化，并可能为特异性靶向关键蛋白质提供一种手段。质谱（MS）提供了一种有前途的检测这种修饰的方法。本综述调查了肾脏疾病中的蛋白质硝化作用，并强调了 MS 检测 SHR 中硝化残基的机会。
