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; 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 萘（NA）和1-硝基苯丙胺（1-NN）是环境空气污染物，通过肺细胞色素P450单加偶加酶和耗尽的谷胱甘肽进行生物活化。反应性代谢产物与细胞蛋白共价结合，并且该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，因为与啮齿动物肺相比，灵长类动物中细胞色素P450单加氧酶的活性降低了。除了成为生物活化毒物的靶标外，气道还是急性炎症反应最易感的部位之一。炎症至少在肝外组织中极大地抑制了细胞色素P450代谢。最近的工作已建立并验证了人类哮喘的灵长类动物模型，该模型涉及暴露于房屋尘螨抗原（HDMA）和臭氧（O3）。因此，这些研究旨在测量恒河猕猴中反应性代谢物蛋白加合物的形成和身份，并确定产生哮喘反应的治疗是否会改变产生的蛋白质加合物的速率或性质。