3 CHLOROTYROSINE, SPECIFIC MARKER OF MYELOPEROXIDASE CATALYZED OXIDATION

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的重要性，但促进氧化的机制 在活体内仍然知之甚少。我们已经探索了这种可能性 其中一条途径涉及髓过氧化物酶，这是一种由 吞噬细胞。髓过氧化物酶是人类已知的唯一一种酶 在生理卤化物下生成强氧化剂HOCl 浓度。暴露于完整髓过氧化物酶的低密度脂蛋白-H2=O2-Cl 该系统对其酪氨酸蛋白残基进行了氯化。 试剂HOCl处理低密度脂蛋白生成3-氯酪氨酸 形成，暗示HOCl2是酶中的中间体 反应蛋白途径。相比之下，3-氯酪氨酸在 被羟基、铜、铁、氯化血红素、葡萄糖氧化的低密度脂蛋白 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 髓过氧化物酶氧化低密度脂蛋白的特异性标志物。检测到离子 3-氯酪氨酸在人类动脉粥样硬化病变中的研究表明 髓过氧化物酶系统催化的卤化反应 吞噬细胞是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. 系统在将低密度脂蛋白转化为致动脉粥样硬化中起着关键作用 形式。

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.