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）的氧化可能是关键