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

• 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
• 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

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 在动脉粥样硬化形成中的重要性，但促进氧化的机制 对体内生物学特性了解甚少。 我们已经研究过 其中一个途径涉及髓过氧化物酶，一种血红素蛋白， 吞噬细胞 髓过氧化物酶是唯一已知的人类酶， 产生HOCl，一种有效的氧化剂，在生理卤素， 浓度的 LDL暴露于完全髓过氧化物酶-H2 =O2-Cl 系统进行氯化其蛋白质酪氨酰残基。 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， 反应途径 相比之下，3-氯酪氨酸是检测不到的， LDL被羟基自由基、铜、铁、氯化血红素、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-氯酪氨酸是一种 髓过氧化物酶对LDL氧化的特异性标志物。 检测离子 人体动脉粥样硬化病变中3-氯酪氨酸的含量表明， 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。 这些发现提高了髓过氧化物酶-H2-C2-Cl 系统在将LDL转化为致动脉粥样硬化的 form.