Deficiency of Myeloperoxidase Increases Infarct Volume and Nitrotyrosine Formation in Mouse Brain
Deficiency of Myeloperoxidase Increases Infarct Volume and Nitrotyrosine Formation in Mouse Brain
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DOI：
10.1097/00004647-200201000-00006
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发表时间：
2002-01
影响因子：
6.3
通讯作者：
S. Takizawa;Y. Aratani;N. Fukuyama;N. Maeda;H. Hirabayashi;H. Koyama;Y. Shinohara;H. Nakazawa
中科院分区：
文献类型：
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作者：
S. Takizawa;Y. Aratani;N. Fukuyama;N. Maeda;H. Hirabayashi;H. Koyama;Y. Shinohara;H. Nakazawa
过氧亚硝酸盐负责体内硝化，而髓过氧化物酶也可以在高NO2−水平下催化蛋白质硝化。髓过氧化物酶介导的酶失活或脂质过氧化的最新报道表明髓过氧化物酶在各种病理条件下的作用。为了阐明髓过氧化物酶在缺血性脑损伤中的作用，作者测量了2小时局灶性脑缺血-再灌注的髓过氧化物酶缺陷或野生型小鼠的硝基酪氨酸形成和梗死体积。再灌注后24小时，髓过氧化物酶缺陷小鼠的梗死体积明显大于野生型小鼠（81 ± 20 mm 3 vs. 52 ± 13 mm 3，P < 0.01），髓过氧化物酶缺陷小鼠梗死区硝基酪氨酸水平高于野生型小鼠（13.4 ± 6.1 μg/mg vs.9.8 ± 4.4 μg/mg，P = 0.13）。再灌注后14 h，髓过氧化物酶缺陷小鼠的硝基酪氨酸水平显著高于野生型小鼠（3.3 ± 2.9 μg/mg vs.1.4 ± 0.4 μg/mg，P < 0.05）。作者得出结论，髓过氧化物酶的缺乏增加了体内缺血性神经元损伤，髓过氧化物酶介导的途径不是脑缺血-再灌注中硝化反应的原因。
Peroxynitrite is responsible for nitration in vivo, whereas myeloperoxidase can also catalyze protein nitration in the presence of high NO2− levels. Recent reports of myeloperoxidase-mediated enzyme inactivation or lipid peroxidation have suggested a role of myeloperoxidase in various pathological conditions. To clarify the role of myeloperoxidase in ischemic brain injury, the authors measured nitrotyrosine formation and infarct volume in myeloperoxidase-deficient or wild-type mice subjected to 2-hour focal cerebral ischemia-reperfusion. Twenty-four hours after reperfusion, infarct volume was significantly larger in myeloperoxidase-deficient mice than in wild-type mice (81 ± 20 mm3 vs. 52 ± 13 mm3, P < 0.01), and nitrotyrosine levels in the infarct region were higher in myeloperoxidase-deficient mice than in wild-type mice (13.4 ± 6.1 μg/mg vs. 9.8 ± 4.4 μg/mg, P = 0.13). Fourteen hours after reperfusion, the nitrotyrosine level was significantly higher in myeloperoxidase-deficient mice than in wild-type mice (3.3 ± 2.9 μg/mg vs. 1.4 ± 0.4 μg/mg, P < 0.05). The authors conclude that the absence of myeloperoxidase increases ischemic neuronal damage in vivo, and that the myeloperoxidase-mediated pathway is not responsible for the nitration reaction in cerebral ischemia-reperfusion.