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975873 
Journal Article 
Abstract 
Myeloperoxidase interaction with peroxynitrite: Chloride deficiency and heme depletion 
Abu-Soud, HM; Galjasevic, S; Maitra, D; Abdulhamid, I 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S132-S132 
English 
WOS:000260867900370 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Myeloperoxidase (MPO) is a hemoprotein that have antibacterial properties through its ability to produce hypochlorous acid (HOCl) when combined with hydrogen peroxide (H2O2) and chloride (Cl−). Normal Cl− concentration in plasma is 100 mM (+ 10 mM) and its concentration in saliva is between 10-50 mM. Salivary MPO is considered a part of the mucosal defense mechanisms of the oral cavity in the relatively low Cl− environment of saliva. Here, we show that Cl− deficiency combined with enhanced peroxynitrite (ONOO−) concentration caused inhibition of MPO through a mechanism that involves heme depletion. in the presence of low Cl− (>50 mM), ONOO− inactivated MPO through the transient complex formation of MPO-Fe-ONOO which is rapidly converted to MPO-Fe(III) through the formation of MPO Compound II. in the presence of H2O2 and low Cl−, MPO heme partially or almost completely depleted as determined by the flattening in the MPO absorbance Soret peak region. Peroxynitrite/H2O2-mediated MPO heme depletion was confirmed by in-gel heme staining which showed approximately 60-70% less heme content compared to control. a non-reducing denaturing SDS PAGE showed no fragmentation or degradation of protein. the MPO heme depletion occurred in a slow rate and independent of ONOO− concentration, suggesting a conformational change in the distal heme pocket of MPO. Myeloperoxidase heme loss was partially or completely prevented by enhancing Cl− concentration, lowering ONOO− concentration, or a combination of both. Peroxynitrite-dependent inhibition of MPO occurred with a wide range of ONOO− and H2O2 concentrations that span various physiological and pathological ranges. Peroxynitrite interaction with MPO may thus serve as a novel mechanism for modulating MPO catalytic activity, influencing the regulation of local inflammatory and infectious events in vivo. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008