کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1910638 | 1046780 | 2009 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Myeloperoxidase interaction with peroxynitrite: chloride deficiency and heme depletion
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Myeloperoxidase (MPO) is a hemoprotein involved in the leukocyte-mediated defense mechanism and uses hydrogen peroxide (H2O2) and chloride (Clâ) to produce hypochlorous acid. In human saliva and in hypochloremic alkalosis syndrome occurring in breast-fed infants, the MPO-H2O2 system functions in a lower Clâ concentration (10-70Â mM) compared to plasma levels (100Â mM) as part of the antibacterial defense system. The impact of low Clâ concentration and exposure to high peroxynitrite (ONOOâ) synthesized from cigarette smoke or oxidative stress on MPO function is still unexplored. Rapid mixing of ONOOâ and MPO caused immediate formation of a transient intermediate MPO Compound II, which then decayed to MPO-Fe(III). Double mixing of MPO with ONOOâ followed by H2O2 caused immediate formation of Compound II, followed by MPO heme depletion, a process that occurred independent of ONOOâ concentration. Peroxynitrite/H2O2-mediated MPO heme depletion was confirmed by HPLC analysis, and in-gel heme staining showing 60-70% less heme content compared to the control. A nonreducing denaturing SDS-PAGE showed no fragmentation or degradation of protein. Myeloperoxidase heme loss was completely prevented by preincubation of MPO with saturating amounts of Clâ. Chloride binding to the active site of MPO constrains ONOOâ binding by filling the space directly above the heme moiety or by causing a protein conformational change that constricts the distal heme pocket, thus preventing ONOOâ from binding to MPO heme iron. Peroxynitrite interaction with MPO may serve as a novel mechanism for modulating MPO catalytic activity, influencing the regulation of local inflammatory and infectious events in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 47, Issue 4, 15 August 2009, Pages 431-439
Journal: Free Radical Biology and Medicine - Volume 47, Issue 4, 15 August 2009, Pages 431-439
نویسندگان
Semira Galijasevic, Dhiman Maitra, Tun Lu, Inga Sliskovic, Ibrahim Abdulhamid, Husam M. Abu-Soud,