EXTRACELLULAR SUPEROXIDE DISMUTASE IN AIRWAY AND PULMONARY VASCULAR BIOLOGY

抗氧化酶在调节肺气道和肺血管中的作用 将对疾病进行评估。在此期间最重要的发现之一 这笔赠款的前一个资助期是细胞外形式的 超氧化物歧化酶(EC-SOD)是一种唯一高效表达的蛋白质。 肺部。发现它主要定位于细胞外。 呼吸道和肺内平滑肌细胞周围的间隙 脉管系统。需要检验的假设是EC-SOD发挥着关键作用 在调节一氧化氮(NO)活性中的作用在肺里。这个 EC-SOD调节NO的可能机制。活动涉及 清除O2-，从而阻止O2-与NO的反应。这个 一氧化氮合酶的分布和物理关系 NO的酶来源。)和EC-SOD在肺和肺组织中的分布 将进行肺血管检查。体外和活体动物 将使用模型来演示EC-SOD在调节呼吸道中的作用 以及肺部的血管紧张度。具体目标是1)创建工具 EC-SOD在动物模型中的研究 EC-SOD的功能有待探讨，2)EC-SOD免疫定位于呼吸道和 肺血管系统，3)一氧化氮合酶在呼吸道的免疫定位 和肺血管系统，4)研究呼吸道支气管运动的机制 张力调节；5)肺血管张力机制的研究 监管。这些拟议的研究有望证明EC-SOD 在调节呼吸道和血管张力方面起着关键作用 阿龙。通过证明这种酶的生理重要性，我们 希望找到治疗糖尿病的新药物疗法 同时涉及呼吸道高反应性和肺血管的疾病 高反应性。

The role of antioxidant enzymes in modulating lung airway and vascular diseases will be evaluated. One of the most important findings during the prior funding period of this grant was that the extracellular form of superoxide dismutase (EC-SOD) is a protein uniquely highly expressed in the lung. It was found to be primarily localized in the extracellular spaces surrounding smooth muscle cells in airways and in the pulmonary vasculature. The hypothesis to be tested is that EC-SOD plays a critical role in regulating the activity of nitric oxide (NO.) in the lung. The possible mechanism for EC-SOD regulation of NO. activity involves scavenging O2- and thereby preventing the reaction of O2- with NO.. The distributions and physical relationships of nitric oxide synthase (the enzymatic source of NO.) and EC-SOD in pulmonary airways and in the pulmonary vasculature will be determined. Both in vitro and in vivo animal models will be used to demonstrate the role of EC-SOD in regulating airway and vascular tone in the lung. The Specific Aims are 1) Create tools for the study of EC-SOD in an animal model that will allow the biological function of EC-SOD to be explored, 2) Immunolocalize EC-SOD in airways and pulmonary vasculature, 3) Immunolocalize nitric oxide synthase in airways and pulmonary vasculature, 4) Study the mechanisms of airway bronchomotor tone regulation, and 5) Study the mechanisms of pulmonary vasculature tone regulation. These proposed studies are expected to demonstrate that EC-SOD plays a critical role in regulating both airway and vascular tone in the lung. By demonstrating the physiologic importance of this enzyme, we expect to identify new pharmacologic therapies for the treatment of diseases involving both airway hyperreactivity and pulmonary vascular hyperreactivity.