Mass spectrometric analysis of HOCl- and free-radical-induced damage to lipids and proteins.
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 alpha-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.
Pitt
Andrew R
AR
Faculty of Biological and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Spickett
Corinne M
CM
D005609:Free Radicals / Q000737:chemistry*; D006997:Hypochlorous Acid / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*
D005609:Free Radicals; D008055:Lipids; D016877:Oxidants; D011506:Proteins; D006997:Hypochlorous Acid