Myeloperoxidase and horseradish peroxidase catalyze tyrosine nitration in proteins from nitrite and hydrogen peroxide
Myeloperoxidase and horseradish peroxidase catalyze tyrosine nitration in proteins from nitrite and hydrogen peroxide
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DOI：
10.1006/abbi.1998.0772
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发表时间：
1998-08-15
影响因子：
3.9
通讯作者：
Beckman, JS
中科院分区：
文献类型：
--
作者：
Sampson, JB;Ye, YZ;Beckman, JS
蛋白质中酪氨酸残基的硝化发生在涉及嗜中性粒细胞和巨噬细胞活化的广泛的炎性疾病中。本文报道了髓过氧化物酶（MPO）和辣根过氧化物酶（HRP）均以亚硝酸根（NO_2 ~-）和过氧化氢（H_2O_2）为底物催化蛋白质中酪氨酸的硝化，MPO对牛血清白蛋白（BSA）的硝化催化效率是HRP的10倍左右，MPO对BSA的硝化不需要氯离子作为辅助因子，生理水平的氯化物没有显着抑制MPO硝化。MPO催化氯离子氧化生成次氯酸（HOCl），而HRP不催化，但HRP也催化过氧化氢加亚硝酸根的硝化反应，因此，HOCl的生成不是酪氨酸硝化反应的必然产物。尽管HOCl加亚硝酸盐可以在简单溶液中硝酸化氨基酸酪氨酸，但在心脏匀浆中没有观察到HOCl加亚硝酸盐的蛋白质硝化，可能是由于HOCl和HOCl加亚硝酸盐的多个替代靶点的存在。相反，MPO使用NO2-加H2 O2催化大鼠心脏匀浆中许多蛋白质的硝化，这表明在体内竞争底物存在下可能发生酪氨酸的过氧化物酶催化硝化。HOCl可以取代H2 O2作为氧化底物，用于由过氧化物酶催化的BSA或组织匀浆的硝化。活化的中性粒细胞可以通过多种机制产生硝基酪氨酸，包括过氧亚硝酸盐、HOCl加亚硝酸盐以及涉及MPO的非氯化物依赖性机制、亚硝酸盐和过氧化氢。(C)北京：科学出版社.
Nitration of tyrosine residues in proteins occurs in a wide range of inflammatory diseases involving neutrophil and macrophage activation. We report that both myeloperoxidase (MPO) and horseradish peroxidase (HRP) utilize nitrite (NO2-) and hydrogen peroxide (H2O2) as substrates to catalyze tyrosine nitration in proteins, MPO was approximately 10 times more effective than HRP as a nitration catalyst of bovine serum albumin (BSA), Nitration of BSA by MPO did not require chloride as a cofactor, Physiologic levels of chloride did not significantly inhibit nitration by MPO. Oxidation of chloride to hypochlorous acid (HOCl) is catalyzed by MPO but not by HRP, yet HRP also catalyzed nitration from hydrogen peroxide plus nitrite, Therefore, HOCl formation was not obligatory for tyrosine nitration. Although HOCl plus nitrite can nitrate the amino acid tyrosine in simple solutions, protein nitration by HOCl plus nitrite was not observed in heart homogenates, probably due to the presence of multiple alternative targets of both HOCl and HOCl plus nitrite, In contrast, MPO catalyzed nitration of many proteins in rat heart homogenates using NO2- plus H2O2, suggesting that peroxidase-catalyzed nitration of tyrosine could occur in the presence of competing substrates in vivo. HOCl could substitute for H2O2 as the oxidizing substrate for nitration of either BSA or tissue homogenates catalyzed by either peroxidase, Activated neutrophils may generate nitrotyrosine by several mechanisms, including peroxynitrite, HOCl plus nitrite, and a chloride-independent mechanism involving MPO, nitrite, and hydrogen peroxide. (C) 1998 Academic Press.