Dalle-Donne Isabella, Scaloni Andrea, Giustarini Daniela, Cavarra Eleonora, Tell Gianluca, Lungarella Giuseppe, Colombo Roberto, Rossi Ranieri, Milzani Aldo
Department of Biology, University of Milan, via Celoria 26, I-20133, Milan, Italy.
Mass Spectrom Rev. 2005 Jan-Feb;24(1):55-99. doi: 10.1002/mas.20006.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.
活性氧(ROS)和活性氮(RNS)在多种人类疾病的发病机制和/或进展过程中发挥作用。蛋白质是氧化/亚硝化损伤的重要分子标志。然而,氧化/亚硝化修饰蛋白的存在是具有因果作用还是仅仅反映继发性附带现象,这一问题通常尚未解决。只有在特定病理生理条件下对修饰蛋白进行直接鉴定和表征,才能解读ROS/RNS诱导的蛋白质修饰所发挥的潜在作用。在过去几年中,基于质谱(MS)的技术为更好地理解疾病过程做出了重要贡献。通过氧化还原蛋白质组学对氧化/亚硝化修饰进行研究,有助于在疾病的病理特征与蛋白质结构和功能异常之间建立联系。基于MS的技术有望在分子医学的新时代发挥作用,特别是在发现氧化/亚硝化应激的诊断生物标志物方面,从而实现疾病的早期检测。事实上,对人类疾病中氧化/亚硝化修饰蛋白的鉴定和表征才刚刚起步。