CHARACTER OF SCHIFF BASE FORMED IN REACTION OF P HYDROXYLPHENYLACETALDEHYDE

羟基苯乙醛反应形成席夫碱的性质

• 批准号: 6486707
• 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/6486707
• 关键词: biological products; biomedical resource; hematology; human tissue; immunology; inflammation; proteins; spectrometry

The adducts that form when aldehydes modify proteins have been implicated in the pathogenesis of vascular disease and aging. Our previous studies indicated that p-hydroxyphenylacetaldehyde (pHA), the major product of L-tyrosine oxidation by the myeloperoxidase-hydrogen peroxide-chloride system of phagocytes, covalently modifies the (-amino group of lysine residues at sites of inflammation. Here, we report that pHA also reacts with the amino group of synthetic phospholipids and red blood cell model systems. Fast atom bombardment mass spectrometric analysis of ethanolamine glycerophospholipid or serine glycerophospholipid incubated with pHA and NaCNBH3 detected covalent adducts that were consistent with reduced phospholipid Schiff base adducts. We confirmed the reaction of the aldehyde with the amino group through 1H NMR and mass spectrometric analysis of polar head groups recovered from the modified and reduced parent lipid. When we exposed phospholipid model systems and cell membranes to physiological levels of L-tyrosine and the myeloperoxidase-hydrogen peroxide-chloride system followed by treatment with NaCNBH3, we obtained reduced Schiff base adducts of pHA with ethanolamine glycerophospholipid and serine glycerophospholipid (pHA-PE and pHA-PS, respectively). The reaction required myeloperoxidase, hydrogen peroxide, L-tyrosine and chloride ion; it was inhibited by catalase or heme poisons, implicating a peroxidase in the pathway. Collectively, these results demonstrate that an aldehyde generated by the myeloperoxidase system of phagocytes can covalently modify the amino groups of ethanolamine glycerophospholipid and serine glycerophospholipid. Because amino glycerophospholipids are critical components of cell membranes and circulating lipoproteins such as LDL, similar reactions may play important roles in the initiation or progression of disease at sites of inflammation.

醛修饰蛋白质时形成的加合物 参与血管疾病和衰老的发病机制。 我们的 先前的研究表明，对羟基苯乙醛（pHA） L-酪氨酸被髓过氧化物酶-氢氧化的主要产物 吞噬细胞的过氧化物-氯化物系统，共价修饰 （-炎症部位赖氨酸残基的氨基。在这里，我们 据报道，pHA 也会与合成的氨基发生反应 磷脂和红细胞模型系统。 快速原子轰击 乙醇胺甘油磷脂或的质谱分析 检测到与 pHA 和 NaCNBH3 孵育的丝氨酸甘油磷脂 与还原磷脂希夫一致的共价加合物 碱加合物。 我们证实了醛与 通过 1H NMR 和极性质谱分析氨基 头基团从修饰和还原的母体脂质中恢复。 当我们暴露磷脂模型系统时 和细胞膜的L-酪氨酸的生理水平 髓过氧化物酶-过氧化氢-氯化物系统，然后 用NaCNBH3处理，我们得到了pHA的还原希夫碱加合物 含有乙醇胺甘油磷脂和丝氨酸甘油磷脂 （分别为 pHA-PE 和 pHA-PS）。 所需反应 髓过氧化物酶、过氧化氢、L-酪氨酸和氯离子；它 被过氧化氢酶或血红素毒物抑制，暗示过氧化物酶 路径。 总的来说，这些结果表明醛 吞噬细胞的髓过氧化物酶系统产生的可共价结合 修饰乙醇胺甘油磷脂和丝氨酸的氨基 甘油磷脂。 因为氨基甘油磷脂至关重要 细胞膜和循环脂蛋白（例如低密度脂蛋白）的成分， 类似的反应可能在引发或 炎症部位的疾病进展。