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: 6665826
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665826
• 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.

我们最近证明，活化的吞噬细胞利用 血红素蛋白髓过氧化物酶、H2O2 和 Cl- 氧化芳香族化合物 氨基酸L-酪氨酸转化为活性醛 对羟基苯乙醛。 形成的产品收率高， 表明其他氨基酸可能类似地被氧化成它们的 炎症部位的吞噬细胞会产生相应的醛。 我们 现在通过以下方式提供该反应普遍性的证据： 证明中性粒细胞利用 髓过氧化物酶-H2O2-Cl-系统可氧化几乎所有常见物质 (-氨基酸生成一系列活性醛。化学 表征表明反应性羰基部分是 髓过氧化物酶在氨基酸氧化过程中产生。 这 使用氨基酸衍生的醛的结构进行了确认 多种质谱方法。 需要生产乙醛 髓过氧化物酶、H2O2、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 因为它添加到 (-氨基酸) 导致形成 预期的醛。 受刺激的人类中性粒细胞同样产生 来自所有类别（-氨基酸）的醛通过受抑制的途径 血红素毒物和过氧化氢酶，涉及髓过氧化物酶和 H2O2 细胞介导的反应。 醛产量占比高达70% 生理条件下受刺激的中性粒细胞产生的 H2O2 氨基酸浓度。 总的来说，这些结果表明 氨基酸衍生的醛代表一类主要的反应性醛类 由活化的吞噬细胞产生的物种。 期间乙醛产生量 氨基酸氧化可能是其重要机制 信号传导和关键靶点的选择性损伤 炎症和血管疾病。