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.

我们最近证明了活化的吞噬细胞采用 血红素蛋白骨髓过氧化物酶H2O2和Cl-氧化芳香族 氨基酸L-酪氨酸到反应性醛 p-羟基苯基甲醛。 该产品的产量高， 表明其他氨基酸可能同样被氧化为 吞噬细胞在炎症部位相应的醛。 我们 现在呈现证据证明这种反应的普遍性 证明中性粒细胞采用 髓过氧化物酶-H2O2-CL系统几乎氧化所有常见 （ - 氨基酸产生一个反应性醛家族。 表征表明反应性羰基部分是 在氨基酸氧化过程中通过骨髓过氧化物酶产生。 这 使用A确认了氨基酸来源的醛结构 多种质谱法。 需要醛产生 脊髓过氧化物酶H2O2，Cl-和氨基酸；它被血红素抑制 毒物和过氧化氢酶。 次氯Ous酸（HOCL）是明显的氧化中间体 因为它是在（ - 氨基酸导致形成的） 预期的醛。 刺激的人类嗜中性粒细胞同样产生 来自所有类别的醛（ - 通过抑制的途径 - 氨基酸 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。 醛生产占70％ 由刺激的嗜中性粒细胞生成的H2O2 氨基酸的浓度。 这些结果共同表明 氨基酸衍生的醛代表了主要的反应性类别 活化的吞噬细胞产生的物种。 醛期间产生 氨基酸氧化可能构成了重要的机制 信号传导和关键目标的选择性损害 炎症和血管疾病。