Biomarkers of myeloperoxidase-derived hypochlorous acid.
Hypochlorous acid is the major strong oxidant generated by neutrophils. The heme enzyme myeloperoxidase catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride. Although myeloperoxidase has been implicated in the tissue damage that occurs in numerous diseases that involve inflammatory cells, it has proven difficult to categorically demonstrate that it plays a crucial role in any pathology. This situation should soon be rectified with the advent of sensitive biomarkers for hypochlorous acid. In this review, we outline the advantages and limitations of chlorinated tyrosines, chlorohydrins, 5-chlorocytosine, protein carbonyls, antibodies that recognize HOCl-treated proteins, and glutathione sulfonamide as potential biomarkers of hypochlorous acid. Levels of 3-chlorotyrosine and 3,5-dichlorotyrosine are increased in proteins after exposure to low concentrations of hypochlorous acid and we conclude that their analysis by gas chromatography and mass spectrometry is currently the best method available for probing the involvement of oxidation by myeloperoxidase in the pathology of particular diseases. The appropriate use of other biomarkers should provide complementary information.Keywords-Free radicals, Myeloperoxidase, Neutrophil oxidant, Hypochlorous acid, Chlorotyrosine, Chlorohydrin, Oxidant biomarker
Winterbourn
C C
CC
Free Radical Research Group, Department of Pathology, Christchurch School of Medicine, Christchurch, New Zealand. christine.winterbourn@chmeds.ac.nz
Kettle
A J
AJ
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D006997:Hypochlorous Acid / Q000032:analysis* / Q000097:blood; D009195:Peroxidase / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D006997:Hypochlorous Acid; D009195:Peroxidase