GLUTATHIONE LEVELS IN AIRWAYS OF INFANT MONKEYS EXP TO O3 WITH & WITHOUT HDMA

幼猴气道中的谷胱甘肽水平 EXP 至 O3

• 批准号: 8172514
• 负责人: DALLAS Melvin HYDE
• 金额: $ 11.41万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172514
• 关键词: Acute; Air Pollutants; Asthma; Binding; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Dermatophagoides Antigens; Exposure to; Extrahepatic; Funding; Glutathione; Grant; Human; Infant; Inflammation; Inflammatory Response; Institution; Lung; Macaca mulatta; Measures; Metabolism; Mixed Function Oxygenases; Modeling; Monkeys; Naphthalene; Naphthalenes; Nature; Ozone; Primates; Process; Proteins; Research; Research Personnel; Resources; Rodent; Rodent Model; Site; Source; Tissues; United States National Institutes of Health; Work; adduct; cell injury; design; protein metabolite; response; toxicant

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Naphthalene (NA) and 1-nitronaphthalene (1-NN) are ambient air pollutants which undergo bioactivation by pulmonary cytochrome P450 monooxygenases and deplete Glutathione. Reactive metabolites become bound covalently to cellular proteins and this process has been implicated in cellular injury associated with these agents in rodent models. The relevance of rodent models in assessing the importance of chemicals which require bioactivation is not clear because of the 10 to 100 fold lower activities of cytochrome P450 monooxygenases in primates compared to rodent lungs. Besides being a target for bioactivated toxicants, the airway is also one of the most susceptible sites for acute inflammatory response. Inflammation results in a strong suppression of cytochrome P450 dependent metabolism at least in extrahepatic tissues. Recent work has established and validated a primate model for human asthma which involves exposure to house dust mite antigen (HDMA) and ozone (O3). Accordingly these studies were designed to measure the formation of, and identity of reactive metabolite protein adducts in rhesus macaques and to determine whether treatments which produce an asthmatic response alter the rates and or nature of protein adducts generated.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 萘 (NA) 和 1-硝基萘 (1-NN) 是环境空气污染物，它们会被肺细胞色素 P450 单加氧酶生物激活并消耗谷胱甘肽。反应性代谢物与细胞蛋白质共价结合，这一过程与啮齿动物模型中与这些药物相关的细胞损伤有关。啮齿动物模型在评估需要生物活化的化学物质的重要性方面的相关性尚不清楚，因为与啮齿动物肺部相比，灵长类动物中细胞色素 P450 单加氧酶的活性低 10 至 100 倍。气道除了是生物活性毒物的目标外，也是最容易发生急性炎症反应的部位之一。炎症至少在肝外组织中导致细胞色素 P450 依赖性代谢的强烈抑制。最近的工作建立并验证了人类哮喘的灵长类动物模型，其中涉及暴露于屋尘螨抗原（HDMA）和臭氧（O3）。因此，这些研究旨在测量恒河猴中反应性代谢物蛋白加合物的形成和特性，并确定产生哮喘反应的治疗是否改变产生的蛋白加合物的速率和/或性质。