EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY
EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY
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DOI：
10.1515/bchm3.1994.375.2.81
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发表时间：
1994-02-01
期刊：
影响因子：
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通讯作者：
BECKMAN, JS
中科院分区：
文献类型：
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作者：
BECKMANN, JS;YE, YZ;BECKMAN, JS
脂蛋白的氧化对于动脉粥样硬化病变的起始和传播是重要的，并且可能涉及来自一氧化氮的次级氧化剂。一氧化氮（NO）以接近扩散极限的速率与超氧化物（O-2）反应。(-))形成强氧化剂过氧亚硝酸盐（ONOO-）。酪氨酸邻位的硝化是过氧亚硝酸根攻击蛋白质的主要产物。用多克隆和单克隆抗体检测福尔马林固定的人冠状动脉粥样硬化病变中的硝基酪氨酸。在粥样硬化沉积物内的泡沫巨噬细胞内和周围明显结合。在早期内膜下脂肪条纹中也观察到硝化。通过与10 mM硝基酪氨酸共孵育完全阻断抗体结合，但不通过等效浓度的氨基酪氨酸或磷酸酪氨酸。硝基酪氨酸的存在表明，来自一氧化氮的氧化剂，如过氧亚硝酸盐在人类动脉粥样硬化中产生，并可能参与其发病机制。
Oxidation of lipoproteins is important for the initiation and propagation of the atherosclerotic lesion and may involve secondary oxidants derived from nitric oxide. Nitric oxide (NO) reacts at near diffusion limited rates with superoxide (O-2.(-)) to form the strong oxidant, peroxynitrite (ONOO-). Nitration on the ortho position of tyrosine is a major product of peroxynitrite attack on proteins. Nitrotyrosine was detected in atherosclerotic lesions of formalin-fixed human coronary arteries with polyclonal and monoclonal antibodies. Binding was pronounced in and around foamy macrophages within the atheroma deposits. Nitration was also observed in early subintimal fatty streaks. Antibody binding was completely blocked by co-incubation with 10mM nitrotyrosine, but not by equivalent concentrations of aminotyrosine or phosphotyrosine. The presence of nitrotyrosine indicates that oxidants derived from nitric oxide such as peroxynitrite are generated in human atherosclerosis and may be involved in its pathogenesis.