Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite - A potential additional, mechanism of nitric oxide-dependent toxicity
Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite - A potential additional, mechanism of nitric oxide-dependent toxicity
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DOI：
10.1074/jbc.272.12.7617
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发表时间：
1997-03-21
影响因子：
4.8
通讯作者：
Cross, CE
中科院分区：
文献类型：
--
作者：
vanderVliet, A;Eiserich, JP;Cross, CE
过氧亚硝酸盐（ONOO-）在炎症性疾病中的参与已经通过在各种炎症组织中检测3-硝基酪氨酸（据称是特征性蛋白质氧化产物）而被牵连。我们在这里表明，亚硝酸盐（NO2-），一氧化氮（NO.）的主要代谢终产物，在过氧化氢（H2 O2）存在下，可被血红素过氧化物酶辣根过氧化物酶、髓过氧化物酶（MPO）和乳过氧化物酶（LPO）氧化，最有可能形成NO2。其也可在炎症过程中促进酪氨酸硝化。MPO催化的NO2-氧化的酚硝化作用仅部分地被氯离子（Cl-）抑制，氯离子是MPO的假定的主要生理底物。事实上，低浓度的NO2-（2-10 μ M）催化MPO介导的Cl-氧化，表现为一氯双酮或4-羟基苯乙酸的氯化增加，最有可能是通过MPO化合物II的还原。在硫氰酸盐（SCN-）存在下也观察到过氧化物酶催化的NO-2氧化，表现为酚硝化，SCN-是哺乳动物过氧化物酶的另一种生理底物，总之，我们的结果表明，N-（O）在生理或病理水平上是哺乳动物过氧化物酶MPO和乳过氧化物酶的底物，通过过氧化物酶催化NO-2的氧化形成NO-2可能提供一个额外的途径，有助于细胞毒性或与NO-产生增加相关的宿主防御。
Involvement of peroxynitrite (ONOO-) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues, We show here that nitrite (NO2-), the primary metabolic end product of a nitric oxide (NO.), can be oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO2., which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO-catalyzed NO2- oxidation is only partially inhibited by chloride (Cl-), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2- (2-10 mu M) catalyze MPO-mediated oxidation of Cl-, indicated by increased chlorination of monochlorodimedon or 4-hydroxyphenylacetic acid, most likely via reduction of MPO compound II, Peroxidase-catalyzed oxidation of NO-2, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN-), an alternative physiological substrate for mammalian peroxidases, Collectively, our results suggest that N--(O), at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO-2 via peroxidase-catalyzed oxidation of NO. may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO' production.