Core D: Oxidative Stress Core

暴露于受污染的超级基金土壤中的细颗粒物和超细颗粒物或危险物质的热处理产生的细颗粒物和超细颗粒物可能会对健康造成危害，如加重肺部和心血管疾病。该计划的目标包括确定粒子产生的活性氧物种(ROS)的参与和氧化应激机制在目标组织内观察到的毒性中的参与。氧化应激核心将为非生物医学项目1和生物医学项目2、4和5提供支持。项目1将确定分子污染物如何与表面反应形成环境持久性自由基(EPFR)以及它们为什么稳定。这一努力的关键是阐明这些粒子本身是否会进行氧化还原循环以产生ROS。该核心将有助于测量在体外粒子系统中产生的ROS。项目5将确定细胞色素P450在颗粒诱导的ROS产生的启动/加剧中的作用。该核心将为从UFP处理的大鼠分离的肺微粒体内ROS和脂质氧化的测量提供支持。项目2 4将通过涉及氧化应激的机制来评估UFP在加剧心脏缺血再灌注损伤以及慢性阻塞性肺疾病中的作用。核心将通过测量ROS的产生和氧化应激来为这些项目服务。该提案描述了将进行的分析和将提供的专业知识。我们将利用最新的技术，但也将使用成熟的方法来衡量必要的端点。重要的是，核心将适应项目不断变化的需求，并将在必要时开发新技术。核心配备了必要的专业知识和人员，核心领导实验室提供的所有相关仪器，包括分光光度计、高效液相色谱和LC-MS/MS，都将提供给核心。核心的优势包括核心领导和人员的专业知识广度，核心人员的可及性/合作性，以及核心和所述项目之间已经进行的强有力的合作。

Exposure to fine particles and ultrafine particles in contaminated Superfund soils or produced from thermal treatment of hazardous substances may present health hazards, such as the exacerbation of pulmonary and cardiovascular diseases. The program objective includes determining the involvement of particle-generated reactive oxygen species (ROS) and oxidative stress mechanisms in toxicities observed within target tissues. The Oxidative Stress Core will provide support for Non-biomedical Project 1 and Biomedical projects 2, 4 and 5. Project 1 will determine how the molecular pollutants react with surfaces to form environmentally-persistent free radicals (EPFR) and why they are stabilized. Critical to this effort is elucidating whether the particles themselves redox-cycle to generate ROS. The core will assist with measurements of ROS produced in particle systems in vitro. Project 5 will determine the role of cytochrome P450 in the initiation/exacerbation of particle-induced ROS production. The core will provide support for the measurements of ROS and lipid oxidation in lung microsomes isolated from UFP-treated rats. Projects 2 and 4 will assess the role of UFP in exacerbating ischemia-reperfusion injury in the heart, as well as chronic obstructive pulmonary disease, through mechanisms involving oxidative stress. The core will service these projects by conducting measurements of ROS production and oxidative stress. This proposal describes assays that will be conducted and expertise to be provided. We will utilize the most current technologies, but will also use well-established approaches to measuring the necessary endpoints. Importantly, the core will adapt to the changing needs of the projects and will develop new techniques as necessary. The core is well equipped with the necessary expertise and personnel, and all relevant instrumentation available in the core Leader's laboratory, including spectrophotometers, HPLC, and LC-MS/MS, will be made available to the core. The strengths of the core include the breadth of expertise of the Core Leader and personnel, the accessibility/cooperativity of the core personnel, and the strong collaboration already in place between the core and the described projects.