NO2 DERIVED POLYPEPTIDE ADDUCTS

肺蛋白质显然是与吸入空气污染物反应的目标 该项目的重点是吸入的分子机制 氧化剂一般会破坏多肽，而多肽对 肺的正常结构和功能，具体地说。氮气 二氧化氮(NO2)及其相关的NO(X)物种就是大气的例子 来自化石燃料燃烧和香烟烟雾的污染物。2号 对大鼠的吸入毒理学研究表明，暴露在NO2中 会导致“实验性肺气肿”。亚硝酸盐的体外暴露 人工合成十肽后暴露重组人α-1- 蛋白水解酶抑制物(通过抑制来保护肺免受肺气肿的影响 中性粒细胞酶)将被用来确定 将这些多肽转化为污染物氧化剂。第二名曝光的 十肽，以及抑制剂，随后是抑制剂和 不饱和碳氢化合物及膜包埋型缓蚀剂分析 用电喷雾电离质谱仪、~(15)N-核磁共振、~(13)C-~(15)N-核磁共振谱和~1H-核磁共振谱 核磁共振和气相色谱将鉴定特定的NO2衍生加合物。 这些研究还将确定不饱和脂肪酸的自氧化 脂肪酸会导致多肽失活，从而减少 龙的防御系统。

Lung proteins are obvious targets for reaction with inhaled air pollutants and the project focuses on the molecular mechanisms by which inhaled oxidants may damage polypeptides, in general, and polypeptides vital to the normal structure and function of the lung, specifically. Nitrogen dioxide (NO2) and its associated NO(x) species are examples of atmospheric pollutants derived- from fossil fuel combustion and cigarette smoke. NO2 inhalation toxicological studies in rats have shown that exposure to NO2 produces an "experimental pulmonary emphysema". In vitro NO2 exposures of synthetic decapeptides followed by exposures of recombinant human alpha-1- proteinase inhibitor (which protects the lung from emphysema by inhibiting a neutrophil enzyme) will be performed to determine the susceptibility of these polypeptides to pollutant oxidants. NO2 exposures of the decapeptides, and of inhibitors, followed by exposures of inhibitors and unsaturated hydrocarbons as well as membrane entrapped inhibitors analyzed by Electrospray Ionization Mass Spectrometry, 15N-NMR,13C-15N-NMR,and 1H- NMR and Gas Chromatography will identify specific NO2 derived adducts. These studies will also determine whether the autoxidation of unsaturated fatty acids contributes to polypeptide inactivation; thus diminishing the lung's defenses.