TRANSGENE TARGETING OF ANTIOXIDANTS AND LUNG INJURY

描述：(摘自作者的摘要)尽管有证据支持 暴露于颗粒物后，肺部发生氧化应激， 人们对活性氧物种的来源知之甚少 它们是在细胞内或细胞外的隔室中产生的 在这种情况下，它们会做出反应并造成有害影响，以及 被修饰的细胞或细胞外靶点(S)。调查人员 假设吸入了环境制剂，这些物质会产生毒性 对肺的影响，通过活性氧物种，在一个高度 时尚界分门别类。取决于增加的隔间 正在遭受氧化应激，某些肺细胞类型可能比 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了。此应用程序将测试 这一假说是通过系统地在体内过表达抗氧化物酶 高度划分的肺特有时尚和研究他们的 吸入性接触对维持肺功能的作用 环境颗粒物(残留油、飞灰、二氧化硅浓缩环境 尘土飞扬，Mt.圣海伦火山灰)，并将针对过度表达 铜、锰、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶对小鼠的影响 肺使用表面活性蛋白C启动子。从这些方面获得的见解 研究可以用来制定预防的新疗法。 和/或治疗颗粒物引起的肺部疾病。

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.