HUMAN NEUTROPHILS EMPLOY MYELOPEROXIDASE H2O2 CL SYS TO OXIDIZE

人类中性粒细胞利用髓过氧化物酶 H2O2 CL 系统进行氧化

• 批准号: 6486706
• 负责人: STANLEY HAZEN
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 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/6486706
• 关键词: biological products; biomedical resource; hematology; human tissue; immunology; inflammation; proteins; spectrometry

We have recently demonstrated that activated phagocytes employ the heme protein myeloperoxidase, H2O2 and Cl- to oxidize the aromatic amino acid L-tyrosine to the reactive aldehyde p-hydroxyphenylacetaldehyde. The product is formed in high yield, suggesting that other amino acids might similarly be oxidized to their corresponding aldehydes by phagocytes at sites of inflammation. We now present evidence for the generality of this reaction by demonstrating that neutrophils employ the myeloperoxidase-H2O2-Cl-system to oxidize nearly all of the common (-amino acids to generate a family of reactive aldehydes. Chemical characterization suggested that reactive carbonyl moieties were generated during amino acid oxidation by myeloperoxidase. The structures of amino acid-derived aldehydes were confirmed using a variety of mass spectrometric methods. Aldehyde production required myeloperoxidase, H2O2, Cl- and an amino acid; it was inhibited by heme poisons and catalase. Hypochlor ous acid (HOCl) was the apparent oxidizing intermediate because its addition to (-amino acids resulted in the formation of the anticipated aldehyde. Stimulated human neutrophils likewise generated aldehydes from all classes of (-amino acids by a pathway inhibited by heme poisons and catalase, implicating myeloperoxidase and H2O2 in the cell-mediated reaction. Aldehyde production accounted for up to 70 % of the H2O2 generated by stimulated neutrophils at physiological concentrations of amino acids. Collectively, these results suggest that amino acid-derived aldehydes represent a major class of reactive species generated by activated phagocytes. Aldehyde production during amino acid oxidation may constitute an important mechanism for signaling and the selective damage of critical targets at sites of inflammation and vascular disease.

我们最近已经证明，激活的吞噬细胞利用 血红素蛋白髓过氧化物酶、H2 O2和Cl-氧化芳香族 氨基酸L-酪氨酸与反应性醛 对羟基苯乙醛 产物以高收率形成， 这表明其他氨基酸可能类似地被氧化成它们的 相应的醛通过吞噬细胞在炎症部位。 我们 现在，我们通过以下方式为这种反应的普遍性提供证据： 证明中性粒细胞利用 髓过氧化物酶-H2 O2-Cl-系统氧化几乎所有常见的 （-氨基酸以产生反应性醛家族。 化学 表征表明，反应性羰基部分是 由髓过氧化物酶在氨基酸氧化过程中产生。 的 氨基酸衍生的醛的结构被确认使用 各种质谱方法。 所需的醛生产 髓过氧化物酶，H2 O2，Cl-和氨基酸;它被血红素抑制 毒物和过氧化氢酶。 次氯酸（HOCl）是表观氧化中间体 因为它与α-氨基酸的加成导致了 预计醛。 刺激的人中性粒细胞同样产生 醛类从所有类别的（-氨基酸的途径抑制 血红素毒物和过氧化氢酶，牵连髓过氧化物酶和H2 O2在 细胞介导反应 醛的产量占比高达70% 刺激中性粒细胞产生的H2 O2在生理 氨基酸的浓度。 总的来说，这些结果表明 氨基酸衍生的醛代表了一种主要的反应性醛， 由激活的吞噬细胞产生的物种。 乙醛生产过程中 氨基酸氧化可能构成一个重要的机制， 信号和选择性损害的关键目标的网站 炎症和血管疾病。