title: Chloramines and hypochlorous acid oxidize erythrocyte peroxiredoxin 2.
abstract: Peroxiredoxin 2 (Prx2) is an abundant thiol protein that is readily oxidized in erythrocytes exposed to hydrogen peroxide. We investigated its reactivity in human erythrocytes with hypochlorous acid (HOCl) and chloramines, relevant oxidants in inflammation. Prx2 was oxidized to a disulfide-linked dimer by HOCl, glycine chloramine (GlyCl), and monochloramine (NH(2)Cl) in a dose-dependent manner. In the absence of added glucose, Prx2 and GSH showed similar sensitivities. Second-order rate constants for the reactions of Prx2 with NH(2)Cl and GlyCl were 1.5 x 10(4) and 8 M(-1) s(-1), respectively. The NH(2)Cl value is approximately 10 times higher than that for GSH, whereas Prx2 is approximately 30 times less sensitive than GSH to GlyCl. Thus, the relative sensitivity of Prx2 to GlyCl is greater in the erythrocyte. Oxidation of erythrocyte Prx2 and GSH was less in the presence of glucose, probably because of recycling. High doses of NH(2)Cl resulted in incomplete regeneration of reduced Prx2, suggesting impairment of the recycling mechanism. Our results show that, although HOCl and chloramines are less selective than H(2)O(2), they nevertheless oxidize Prx2. Exposure to these inflammatory oxidants will result in Prx2 oxidation and could compromise the erythrocyte's ability to resist damaging oxidative insult.
authors.affiliation: Department of Pathology, University of Otago at Christchurch, Christchurch 8140, New Zealand.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Stacey
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Peskin
authors.forename: Margreet C
authors.initials: MC
authors.lastname: Vissers
authors.forename: Christine C
authors.initials: CC
authors.lastname: Winterbourn
mesh_terms: D002700:Chloramines / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D054464:Peroxiredoxins / Q000378:metabolism*; D012016:Reference Values
chemical_list: D002700:Chloramines; D006997:Hypochlorous Acid; C086065:PRDX2 protein, human; D054464:Peroxiredoxins