Tyrosine Nitration of Prostacyclin Synthase

前列环素合酶的酪氨酸硝化

• 批准号: 6538025
• 负责人: Aimee Leigh Landar
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6538025
• 关键词: atherosclerosis; enzyme mechanism; enzyme structure; epitope mapping; inflammation; nitric oxide; oxidative stress; peroxynitrites; postdoctoral investigator; prostaglandin endoperoxide synthase; tyrosine

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. .

描述（申请人？促炎症反应是一个重要的过程， 动脉粥样硬化病变和其他病理生理学的发展 条件在动脉粥样硬化病变中，过氧亚硝酸盐，由 一氧化氮与超氧阴离子、硝酸盐蛋白质对酪氨酸的反应 残基这个项目有两个目标，将测试假设， 过氧亚硝酸盐通过硝化激活内皮中的促炎状态， 使前列环素合酶失活。内皮细胞中的这种关键酶 在其活性位点附近的酪氨酸430处易于过氧亚硝酸根硝化。 具体目标1是利用噬菌体展示的强大方法， 链抗体，开发新的抗体， 硝基酪氨酸表位，以及前列环素中的硝化酪氨酸430 合成酶具体目标2是评估剪切应力是否也硝酸盐， 使前列环素合酶失活，导致促炎性细胞因子增加， 前列环素前体，PGH2。.