TRANSGENE TARGETING OF ANTIOXIDANTS AND LUNG INJURY

描述：（来自作者摘要）尽管有支持性证据， 氧化应激发生在肺颗粒暴露后， 对活性氧的来源知之甚少， 细胞或细胞外区室，它们在其中产生，区室 它们在其中起反应并造成有害影响， 修饰的细胞或细胞外靶标。 调查人员 假设吸入环境因素，发挥其毒性， 对肺的影响，通过活性氧，这样做，在一个高度 划分的时尚。 取决于增加的车厢 氧化应激正在受到，某些肺细胞类型可能更多 容易耗尽其分隔的抗氧化剂储备，因此 证明他们受伤的风险增加。 该应用程序将测试 这一假设是通过系统性地过度表达抗氧化酶， 高度分隔的肺特异性方式，并研究其 对维持吸入性暴露后肺功能的贡献 环境颗粒（残油飞灰、二氧化硅浓缩的环境颗粒） 达斯特山圣海伦火山灰），并将针对过度的 CuZn-SOD、Mn-SOD、EC-SOD、过氧化氢酶和谷胱甘肽过氧化物酶对小鼠的影响 肺使用表面活性剂蛋白C启动子。 从中获得的见解 研究可用于制定新的治疗方法， 和/或治疗颗粒诱导的肺病。

DESCRIPTION: (From the authors' abstract) Despite supportive evidence for oxidative stress occurring in the lung following particle exposures, there is little known about the source of the reactive oxygen species, the cellular or extracellular compartment they are produced in, the compartment in which they react and cause their deleterious effects, as well as the cellular or extracellular target(s) which are modified. The investigators hypothesize that inhaled environmental agents, which exert their toxic effects on the lung, via reactive oxygen species, do so in a highly compartmentalized fashion. Depending on the compartment where increased oxidative stress is being subjected, certain lung cell-types may be more vulnerable to depleting their compartmentalized antioxidant reserves, thus proving them to be at increased risk for injury. This application will test this hypothesis by systematically overexpressing antioxidant enzymes in a highly compartmentalized lung-specific fashion and studying their contribution to preserving lung function following inhalational exposure to environmental particles (residual oil fly ash, silica concentrated ambient dust, Mt. St. Helen's volcanic ash), and will target the overexpression of CuZn-SOD, Mn-SOD, EC-SOD, catalase, and glutathione peroxidase to the mouse lung using the surfactant protein C promoter. Insights gained from these studies could be used for formulating novel therapies for the prevention and/or treatment of particle-induced lung disease.