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: 8357246
• 负责人: DALLAS Melvin HYDE
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357246
• 关键词: Acute; Air Pollutants; Asthma; Binding; California; Chemicals; Cytochrome P450; Dermatophagoides Antigens; Exposure to; Extrahepatic; Funding; Glutathione; Grant; Human; Infant; Inflammation; Inflammatory Response; Lung; Macaca mulatta; Measures; Metabolism; Mixed Function Oxygenases; Modeling; Monkeys; Naphthalene; National Center for Research Resources; Nature; Ozone; Primates; Principal Investigator; Process; Proteins; Research; Research Infrastructure; Resources; Rodent; Rodent Model; Site; Source; Tissues; United States National Institutes of Health; Work; adduct; cell injury; cost; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 萘（NA）和1-硝基萘（1-NN）是环境空气污染物，它们通过肺细胞色素P450单加氧酶进行生物活化并消耗谷胱甘肽。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品的重要性方面的相关性尚不清楚，因为灵长类动物的细胞色素P450单加氧酶活性比啮齿动物肺低10至100倍。除了是生物活化毒物的靶点外，气道也是急性炎症反应最敏感的部位之一。炎症导致至少在肝外组织中细胞色素P450依赖性代谢的强烈抑制。最近的工作已经建立和验证了一个灵长类动物模型，人类哮喘，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产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所产生的蛋白加合物的速率和/或性质。