Tyrosine Nitration of Prostacyclin Synthase

描述(申请者？S摘要)：促炎是一个重要的过程 动脉粥样硬化病变和其他病理生理学的进展 条件。在动脉粥样硬化病变中，过氧亚硝酸盐是由 一氧化氮、超氧化物和硝酸盐蛋白质与酪氨酸的反应 残留物。这个项目有两个目标，它们将检验这一假设 过氧亚硝酸盐通过硝化和激活内皮细胞的致炎状态 前列环素合酶失活。内皮细胞中的这种关键酶是不同寻常的 对酪氨酸430活性部位附近的过氧亚硝酸硝化反应敏感。 具体目标1是使用功能强大的噬菌体展示单链 链抗体以开发识别小分子的新抗体 前列环素中的硝基酪氨酸表位和硝化酪氨酸430 合成酶。具体目标2是评估剪切力是否也硝化和 使前列环素合成酶失活，导致促炎症反应增加 前列环素前体PGH2。。

DESCRIPTION (Applicant?s abstract):Proinflammation is an important process in the development of atherosclerotic lesions and other pathophysiological conditions. In atherosclerotic lesions, peroxynitrite, which is formed by the reaction of nitric oxide and superoxide, nitrates proteins on tyrosine residues. This project has two aims that will test the hypothesis that peroxynitrite activates a proinflammatory state in endothelium by nitrating and inactivating prostacyclin synthase. This key enzyme in endothelium is unusually susceptible to peroxynitrite nitration at tyrosine 430 near its active site. Specific aim 1 is to use the powerful methodology of phage display of single chain antibodies to develop new antibodies that recognize the small nitrotyrosine epitope, as well as nitrated tyrosine 430 in prostacyclin synthase. Specific aim 2 is to assess whether shear stress also nitrates and inactivates prostacyclin synthase, resulting in the increase of proinflammatory prostacyclin precursor, PGH2. .