Myeloperoxidase has directly-opposed effects on nitration reaction - Study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice
Myeloperoxidase has directly-opposed effects on nitration reaction - Study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice
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DOI：
10.1080/1071576031000099830
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发表时间：
2003-05-01
影响因子：
3.3
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Ichimori, K;Fukuyama, N;Suzuki, K
髓过氧化物酶（MPO）在高浓度亚硝酸盐存在下催化硝化反应生成硝基酪氨酸，硝基酪氨酸是NO的代谢产物。这与我们以前在人白细胞研究中发现的MPO抑制是苯酚硝化所必需的相反。为了阐明MPO的作用，我们利用MPO缺陷的人白细胞和MPO敲除小鼠。即使在没有外源性添加亚硝酸盐，高硝化产物中观察到MPO缺陷的白细胞。在缺血/再灌注损伤的肝脏中，MPO基因敲除小鼠产生的硝基酪氨酸量显著高于正常小鼠。这些结果清楚地表明，MPO抑制体内硝化产物的积累。进一步的实验表明，MPO可以在谷胱甘肽存在下降解硝基酪氨酸。因此，MPO诱导的硝化产物降解可能导致低估了体内产生的硝化产物。因此，MPO在生理亚硝酸盐条件下可能主要作用于硝基酪氨酸，对硝基酪氨酸的损伤具有保护作用。
Myeloperoxidase (MPO) catalyzes a nitration reaction to form nitrotyrosine in the presence of high nitrite, the metabolite of NO. Human leukocyte was shown to cause phenolic nitration using released MPO as a catalyst in the presence of nitrite. It opposes our previous finding that inhibition of MPO was essential for phenol nitration in human leukocyte study. To clarify the role of MPO, we utilized MPO-deficient human leukocytes and MPO-knockout mice. Even in the absence of exogenously added nitrite, high nitration product was observed in MPO-deficient leukocytes. In liver subjected to ischemia/reperfusion injury, a significantly higher amount of nitrotyrosine was produced in MPO-knockout mice than in normal mice. These results clearly demonstrate that MPO inhibits the accumulation of nitration products in vivo. Further experiments showed that MPO could degrade nitrotyrosine in the presence of glutathione. Thus, MPO-induced degradation of nitration products may cause the underestimation of the nitration product generated in vivo. We conclude that MPO may act predominantly to scavenge nitrotyrosine under physiological nitrite condition, and protect against injurious effect of nitrotyrosine.