Peroxynitrite efficiently mediates the interconversion of redox intermediates of myeloperoxidase
Peroxynitrite efficiently mediates the interconversion of redox intermediates of myeloperoxidase
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DOI：
10.1016/j.bbrc.2005.09.138
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发表时间：
2005-11-25
影响因子：
3.1
通讯作者：
Obinger, C
中科院分区：
文献类型：
--
作者：
Furtmüller, PG;Jantschko, W;Obinger, C
一氧化氮衍生的氧化剂（例如，过氧亚硝酸根）被认为参与作为正常宿主防御的一部分的抗微生物活性，而且还参与炎性病症中的氧化组织损伤。血红素酶髓过氧化物酶（MPO）也有类似的作用，MPO是多形核白细胞中最丰富的蛋白质，是先天免疫系统的终末吞噬效应细胞。伴随产生过氧亚硝酸盐和释放的毫摩尔MPO的吞噬过程中的特征事件。为了了解MPO和过氧亚硝酸盐之间的相互作用模式，我们已经进行了全面的停流调查MPO和过氧亚硝酸盐的所有生理相关的氧化还原中间体之间的反应。铁（III）MPO和铁（II）MPO在两相反应中通过过氧亚硝酸盐快速转化为化合物II，计算的速率常数分别为（6.8 +/- 0.1）× 10（6）M-1 s（-1）和（1.3 +/- 0.2）× 10（6）M-1 s（-1）（pH 7.0和25 ℃）。除了过氧亚硝酸根的这些单电子和双电子还原反应（其产生二氧化氮和亚硝酸根）之外，在由过氧亚硝酸根介导的化合物I在pH 7.0 [（7.6 +/- 0. 1)x 10（6）M-1 S-1]。此外，过氧亚硝酸盐诱导从化合物III到化合物II的稳态转变，速率为（1.0 +/- 0.3）x 10（4）M-1 s（-1）。因此，MPO的各种氧化态之间的相互转换，这是由过氧亚硝酸盐提示是显着的。反应机制提出和生理相关性进行了讨论。(c)2005年爱思唯尔公司All rights reserved.
Nitric oxide-derived oxidants (e.g., peroxynitrite) are believed to participate in antimicrobial activities as part of normal host defenses but also in oxidative tissue injury in inflammatory disorders. A similar role is ascribed to the heme enzyme myeloperoxidase (MPO), the most abundant protein of polymorphonuclear leukocytes, which are the terminal phagocytosing effector cells of the innate immune system. Concomitant production of peroxynitrite and release of millimolar MPO are characteristic events during phagocytosis. In order to understand the mode of interaction between MPO and peroxynitrite, we have performed a comprehensive stopped-flow investigation of the reaction between all physiological relevant redox intermediates of MPO and peroxynitrite. Both iron(III) MPO and iron(II) MPO are rapidly converted to compound II by peroxynitrite in monophasic reactions with calculated rate constants of (6.8 +/- 0.1) X 10(6) M-1 s(-1) and (1.3 +/- 0.2) x 10(6) M-1 s(-1), respectively (pH 7.0 and 25 degrees C). Besides these one- and two-electron reduction reactions of peroxynitrite, which produce nitrogen dioxide and nitrite, a one-electron oxidation to the oxoperoxonitrogen radical must occur in the fast monophasic transition of compound I to compound II mediated by peroxynitrite at pH 7.0 [(7.6 +/- 0. 1) x 10(6) M-1 S-1]. In addition, peroxynitrite induced a steady-state transition from compound III to compound II with a rate of (1.0 +/- 0.3) x 10(4) M-1 s(-1). Thus, the interconversion among the various oxidation states of MPO that is prompted by peroxynitrite is remarkable. Reaction mechanisms are proposed and the physiological relevance is discussed. (c) 2005 Elsevier Inc. All rights reserved.