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Mass spectrometric analysis of hocl- and free-radical-induced damage to lipids and proteins

机译:质谱分析整体和自由基引起的脂质和蛋白质损伤

摘要

In inflammatory diseases, release of oxidants leads to oxidative damage to biomolecules. HOCl (hypochlorous acid), released by the myeloperoxidase/H2O2/Cl− system, can cause formation of phospholipid chlorohydrins, or α-chloro-fatty aldehydes from plasmalogens. It can attack several amino acid residues in proteins, causing post-translational oxidative modifications of proteins, but the formation of 3-chlorotyrosine is one of the most stable markers of HOCl-induced damage. Soft-ionization MS has proved invaluable for detecting the occurrence of oxidative modifications to both phospholipids and proteins, and characterizing the products generated by HOCl-induced attack. For both phospholipids and proteins, the application of advanced mass spectrometric methods such as product or precursor ion scanning and neutral loss analysis can yield information both about the specific nature of the oxidative modification and the biomolecule modified. The ideal is to be able to apply these methods to complex biological or clinical samples, to determine the site-specific modifications of particular cellular components. This is important for understanding disease mechanisms and offers potential for development of novel biomarkers of inflammatory diseases. In the present paper, we review some of the progress that has been made towards this goal. (Abstract copied from Biochemical Society web site: http://www.biochemsoctrans.org/bst/036/bst0361077.htm)
机译:在炎性疾病中,氧化剂的释放导致生物分子的氧化损伤。髓过氧化物酶/ H2O2 / Cl-系统释放的HOCl(次氯酸)可导致缩醛磷脂形成磷脂氯醇或α-氯脂肪醛。它可以攻击蛋白质中的几个氨基酸残基,引起蛋白质的翻译后氧化修饰,但是3-氯酪氨酸的形成是HOCl诱导的损伤的最稳定的标志之一。事实证明,软电离质谱对于检测磷脂和蛋白质的氧化修饰的发生以及表征HOCl诱导的攻击产生的产物具有无价的价值。对于磷脂和蛋白质,先进的质谱方法(例如产物或前体离子扫描和中性损失分析)的应用可以产生有关氧化修饰和生物分子修饰的特定性质的信息。理想的是能够将这些方法应用于复杂的生物学或临床样品,以确定特定细胞成分的位点特异性修饰。这对于理解疾病机理很重要,并为开发炎症性疾病的新型生物标志物提供了潜力。在本文中,我们回顾了在实现该目标方面取得的一些进展。 (摘录自生物化学协会网站:http://www.biochemsoctrans.org/bst/036/bst0361077.htm)

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    Pitt A.R.; Spickett C.M.;

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