DiMarco Theresa, Giulivi Cecilia
Department of Molecular Biosciences, University of California, Davis, California 95616, USA.
Mass Spectrom Rev. 2007 Jan-Feb;26(1):108-20. doi: 10.1002/mas.20109.
Dityrosine is a fluorescent molecule formed as a result of normal posttranslational processing. In many structural proteins, dityrosine confers resistance to proteolysis and physicochemical trauma as a stabilizing crosslink. Dityrosine has also been found in oxidative/nitrative stress under a variety of conditions and biological systems. In this regard, it has been used as an important biomarker for oxidatively modified proteins during UV and gamma-irradiation, aging, and exposure to oxygen free radicals, nitrogen dioxide, peroxynitrite, and lipid hydroperoxides. Renewed interest in dityrosine and other tyrosine oxidation products as clinical indicators of oxidative modification has driven the development of important techniques for the specific analysis and quantification of these molecules. The presence of elevated levels of dityrosine in mammalian tissue and urine samples has been measured by chromatographic separation followed by mass spectrometry GC-MS and HPLC-MS/MS. Increases in dityrosine levels have been associated with pathologies such as eye cataracts, atherosclerosis, acute inflammation, and Alzheimer's disease. The continued development of, and increased accessibility to, improved mass spectrometric instrumentation will expand the capability, feasibility, and sensitivity with which specific biomarkers like dityrosine can be measured.
二酪氨酸是正常翻译后加工过程中形成的一种荧光分子。在许多结构蛋白中，二酪氨酸作为一种稳定的交联键赋予蛋白质抗蛋白水解和物理化学损伤的能力。在各种条件和生物系统下的氧化/硝化应激中也发现了二酪氨酸。在这方面，它已被用作紫外线和γ射线辐射、衰老以及暴露于氧自由基、二氧化氮、过氧亚硝酸盐和脂质氢过氧化物期间氧化修饰蛋白的重要生物标志物。对二酪氨酸和其他酪氨酸氧化产物作为氧化修饰临床指标的重新关注推动了对这些分子进行特异性分析和定量的重要技术的发展。通过色谱分离后接质谱（气相色谱 - 质谱联用和液相色谱 - 串联质谱联用）已检测到哺乳动物组织和尿液样本中二酪氨酸水平升高。二酪氨酸水平的升高与诸如白内障、动脉粥样硬化、急性炎症和阿尔茨海默病等病理状况有关。改进的质谱仪器的持续发展以及其可及性的提高将扩大测量二酪氨酸等特定生物标志物的能力、可行性和灵敏度。
