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：
6486703
负责人：
STANLEY HAZEN
金额：
$ 15.75万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2002-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6486703
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）的氧化可能是关键在动脉粥样硬化形成中很重要，但促进氧化的机制体内仍然知之甚少。我们探索过这种可能性其中一条途径涉及髓过氧化物酶，这是一种由吞噬细胞。髓过氧化物酶是唯一已知的人类酶与生理卤化物生成HOCl，一种有效的氧化剂浓度。 LDL暴露于完全髓过氧化物酶-H2=O2-Cl 系统对其蛋白质酪氨酰残基进行了氯化处理。用 HOCl 试剂处理 LDL 产生 3-氯酪氨酸形成，暗示 HOCl 作为酶促反应的中间体反应素途径。相比之下，3-氯酪氨酸在低密度脂蛋白被羟基自由基、铜、铁、血红素、葡萄糖氧化，过氧亚硝酸盐、辣根过氧化物酶、乳过氧化物酶或脂氧合酶。这些结果表明 3-氯酪氨酸是髓过氧化物酶氧化 LDL 的特异性标记物。检测离子 3-c 氯酪氨酸在人类动脉粥样硬化病变中的含量表明髓过氧化物酶系统催化的卤化反应吞噬细胞构成体内蛋白质氧化的一种途径。这些发现提出了髓过氧化物酶-H2-C2-Cl的可能性系统在将 LDL 转化为致动脉粥样硬化的过程中发挥着关键作用形式。