Myeloperoxidase interaction with peroxynitrite: chloride deficiency and heme depletion.
Myeloperoxidase interaction with peroxynitrite: chloride deficiency and heme depletion.
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DOI：
10.1016/j.freeradbiomed.2009.05.017
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发表时间：
2009-08-15
影响因子：
7.4
通讯作者：
Abu-Soud, Husam M.
中科院分区：
文献类型：
--
作者：
Galijasevic, Semira;Maitra, Dhiman;Lu, Tun;Sliskovic, Inga;Abdulhamid, Ibrahim;Abu-Soud, Husam M.
髓过氧化物酶（MPO）是一种血红素蛋白，参与白细胞介导的防御机制，并利用过氧化氢（H2 O2）和氯离子（Cl-）产生次氯酸。在人类唾液和母乳喂养婴儿中发生的低血糖性腹泻综合征中，MPO-H2 O2系统作为抗菌防御系统的一部分在与血浆水平（100 mM）相比更低的Cl-浓度（10-70 mM）下起作用。低Cl-浓度和暴露于香烟烟雾或氧化应激合成的高过氧亚硝酸盐（ONOO-）对MPO功能的影响尚未研究。ONOO-和MPO的快速混合引起瞬时中间MPO化合物II的立即形成，然后衰变为MPO-Fe（III）。MPO与ONOO-，然后H2 O2的双重混合引起立即形成的化合物II，然后MPO血红素耗尽，发生的过程独立于ONOO-浓度。通过HPLC分析和凝胶内血红素染色证实过氧亚硝酸盐/H2 O2介导的MPO血红素消耗，与对照相比，血红素含量减少60-70%。非还原变性SDS PAGE显示蛋白质无断裂或降解。髓过氧化物酶血红素损失完全防止MPO与饱和量的Cl-预孵育。氯离子与MPO活性位点的结合通过填充血红素部分正上方的空间或通过引起蛋白质构象变化来限制ONOO-结合，从而阻止ONOO-与MPO血红素铁结合。过氧亚硝酸盐与MPO的相互作用可能是一种调节MPO催化活性的新机制，影响体内局部炎症和感染事件的调节。
Myeloperoxidase (MPO) is a hemoprotein, involved in the leukocyte mediated defense mechanism, and uses hydrogen peroxide (H2O2) and chloride (Cl-) to produce hypochlorous acid. In human saliva and hypochloremic alkalosis syndrome occurring in breast fed infants, the MPO-H2O2 system functions in lower Cl- concentration (10-70 mM) compared to plasma levels (100 mM) as part of the antibacterial defense system. The impact of low Cl- concentration and exposure to high peroxynitrite (ONOO-) synthesized from cigarette smoke or oxidative stress on MPO function is still unexplored. Rapid mixing of ONOO- and MPO caused immediate formation of a transient intermediate MPO Compound II which then decayed to MPO-Fe (III). Double mixing of MPO with ONOO- followed by H2O2 caused immediate formation of Compound II followed by MPO heme depletion, a process that occured independent of ONOO- 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 non-reducing denaturing SDS PAGE showed no fragmentation or degradation of protein. Myeloperoxidase heme loss was completely prevented by pre-incubation of MPO with saturated amounts of Cl-. Chloride binding to the active site of MPO constrains ONOO- 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 ONOO- 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.
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DOI：
10.1046/j.1432-1327.2000.01491.x
发表时间：
2000-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Furtmüller, PC;Obinger, C;Dunford, HB
通讯作者：
Dunford, HB
DOI：
10.1073/pnas.0308393100
发表时间：
2004-03-09
影响因子：
11.1
作者：
Fischer, H;Schwarzer, C;Illek, B
通讯作者：
Illek, B
DOI：
10.1016/j.bbrc.2005.09.138
发表时间：
2005-11-25
影响因子：
3.1
作者：
Furtmüller, PG;Jantschko, W;Obinger, C
通讯作者：
Obinger, C
影响因子：
7.4
作者：
Galijasevic, Semira;Abdulhamid, Ibrahim;Abu-Soud, Husam M.
通讯作者：
Abu-Soud, Husam M.
影响因子：
2.9
作者：
Abu-Soud, HM;Raushel, FA;Hazen, SL
通讯作者：
Hazen, SL