title: Reactivity of selenium-containing compounds with myeloperoxidase-derived chlorinating oxidants: Second-order rate constants and implications for biological damage.
abstract: Hypochlorous acid (HOCl) and N-chloramines are produced by myeloperoxidase (MPO) as part of the immune response to destroy invading pathogens. However, MPO also plays a detrimental role in inflammatory pathologies, including atherosclerosis, as inappropriate production of oxidants, including HOCl and N-chloramines, causes damage to host tissue. Low molecular mass thiol compounds, including glutathione (GSH) and methionine (Met), have demonstrated efficacy in scavenging MPO-derived oxidants, which prevents oxidative damage in vitro and ex vivo. Selenium species typically have greater reactivity toward oxidants compared to the analogous sulfur compounds, and are known to be efficient scavengers of HOCl and other hypohalous acids produced by MPO. In this study, we examined the efficacy of a number of sulfur and selenium compounds to scavenge a range of biologically relevant N-chloramines and oxidants produced by both isolated MPO and activated neutrophils and characterized the resulting selenium-derived oxidation products in each case. A dose-dependent decrease in the concentration of each N-chloramine was observed on addition of the sulfur compounds (cysteine, methionine) and selenium compounds (selenomethionine, methylselenocysteine, 1,4-anhydro-4-seleno-L-talitol, 1,5-anhydro-5-selenogulitol) studied. In general, selenomethionine was the most reactive with N-chloramines (k2 0.8-3.4×10(3)M(-1) s(-1)) with 1,5-anhydro-5-selenogulitol and 1,4-anhydro-4-seleno-L-talitol (k2 1.1-6.8×10(2)M(-1) s(-1)) showing lower reactivity. This resulted in the formation of the respective selenoxides as the primary oxidation products. The selenium compounds demonstrated greater ability to remove protein N-chloramines compared to the analogous sulfur compounds. These reactions may have implications for preventing cellular damage in vivo, particularly under chronic inflammatory conditions.
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW 2042, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Carroll
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW 2042, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Pattison
authors.affiliation: Centre for Forensic Science, University of Technology Sydney, Broadway, Sydney, NSW 2007, Australia.
authors.forename: Shanlin
authors.initials: S
authors.lastname: Fu
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, VIC 3010, Australia.
authors.forename: Carl H
authors.initials: CH
authors.lastname: Schiesser
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW 2042, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200, Denmark.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW 2042, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: clare.hawkins@hri.org.au.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Hawkins
mesh_terms: D002700:Chloramines / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry*; D007700:Kinetics; D016877:Oxidants / Q000737:chemistry*; D009195:Peroxidase / Q000737:chemistry*; D018036:Selenium Compounds / Q000737:chemistry*
chemical_list: D002700:Chloramines; D016166:Free Radical Scavengers; D016877:Oxidants; D018036:Selenium Compounds; D009195:Peroxidase
keywords: Hypochlorous acid; Inflammation; Myeloperoxidase; N-Chloramines; Oxidation; Selenium