Myeloperoxidase interaction with peroxynitrite: Chloride deficiency and heme depletion
Abu-Soud, HM; Galjasevic, S; Maitra, D; Abdulhamid, I
HERO ID
975873
Reference Type
Journal Article
Subtype
Abstract
Year
2008
Language
English
| HERO ID | 975873 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2008 |
| Title | Myeloperoxidase interaction with peroxynitrite: Chloride deficiency and heme depletion |
| Authors | Abu-Soud, HM; Galjasevic, S; Maitra, D; Abdulhamid, I |
| Journal | Free Radical Biology and Medicine |
| Volume | 45 |
| Issue | Suppl. |
| Page Numbers | S132-S132 |
| Abstract | 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. |
| Wosid | WOS:000260867900370 |
| Url | http://www.sciencedirect.com/science/article/pii/S089158490800631X |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Indianapolis, IN |
| Conference Name | Society for Free Radical Biology and Medicine 15th Annual Meeting |
| Conference Date | November 19-23, 2008 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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