3 CHLOROTYROSINE, SPECIFIC MARKER OF MYELOPEROXIDASE CATALYZED OXIDATION

3 氯酪氨酸，髓过氧化物酶催化氧化的特异性标记物

基本信息

批准号：
6336773
负责人：
STANLEY HAZEN
金额：
$ 0.6万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-08-01 至 2001-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6336773
关键词：
biomedical resource female human subject human tissue male musculoskeletal system physical fitness proteins spectrometry

项目摘要

Oxidation of low density lipoprotein (LDL) may be of pivotal importance in atherogenesis, but the mechanisms that promote oxidation in vivo remain poorly understood. We have explored the possibility that one pathway involves myeloperoxidase, a heme protein secreted by phagocytes. Myeloperoxidase is the only human enzyme known to generate HOCl, a potent oxidizing agent, at physiological halide concentrations. LDL exposed to the complete myeloperoxidase-H2=O2-Cl system underwent chloriantion of its protein tyrosyl residues. Treatment of LDL with reagent HOCl resulted in 3-chlorotyrosine formation, implicating HOCl as an intermediate in the enzymatic reactin pathway. In contrast, 3-chlorotyrosine was undetectable in LDL oxidized by hydroxyl radical, copper, iron, hemin, glucose, peroxynitrite, horseradish peroxidase, lactoperoxidase or lipoxygenase. These results indicate that 3-chlorotyrosine is a specific marker for LDL oxidation by myeloperoxidase. The detect ion of 3-c hlorotyrosine in human atherosclerotic lesions indicates that halogenation reactions catalyzed by the myeloperoxidase system of phagocytes constitute one pathway for protein oxidation in vivo. These findings raise the possibility that the myeloperoxidase-H2-C2-Cl system plays a critical role in converting LDL into an atherogenic form.

低密度脂蛋白（LDL）的氧化可能是关键的在动脉粥样硬化中的重要性，但是促进氧化的机制体内的理解仍然很差。我们已经探索了可能性那一条途径涉及髓过氧化物酶，一种血红素蛋白，由血红素蛋白分泌吞噬细胞。脊髓过氧化物酶是唯一已知的人类酶在生理卤化物上生成一种有效的氧化剂HOCL（一种有效的氧化剂）浓度。暴露于完整的髓过氧化物酶-H2 = O2-CL的LDL 系统接受其蛋白酪酶残基的氯化。用试剂HOCL治疗LDL导致3-氯托氏菌素形成，将HOCL作为酶促中的中间体反应蛋白途径。相比之下，3-氯托酪氨酸是无法检测到的 LDL被羟基自由基，铜，铁，半葡萄糖，葡萄糖，过氧亚硝酸盐，辣根过氧化物酶，乳酸氧化酶或脂氧合酶。这些结果表明3-氯吡啶酪氨酸是一个通过骨髓过氧化物酶进行LDL氧化的特异性标记。检测离子人动脉粥样硬化病变中的3-C Hlorotyrosine表明卤代反应由髓过氧化物酶系统催化吞噬细胞构成体内蛋白质氧化的一种途径。这些发现增加了髓过氧化物酶-H2-C2-CL的可能性系统在将LDL转化为动脉粥样硬化中起着至关重要的作用形式。