NO2 DERIVED POLYPEPTIDE ADDUCTS

肺蛋白是与吸入的空气污染物反应的明显目标 该项目的重点是吸入的分子机制， 一般来说，氧化剂可能会损害多肽， 肺的正常结构和功能氮 二氧化物（NO2）及其相关的NO（x）物种是大气中的 来自化石燃料燃烧和香烟烟雾的污染物。NO2 大鼠吸入毒理学研究表明， 会产生“实验性肺气肿”体外NO2暴露 合成十肽，然后暴露于重组人α-1- 蛋白酶抑制剂（通过抑制 一种中性粒细胞酶），以确定 这些多肽污染氧化剂。NO2暴露 十肽和抑制剂，然后暴露于抑制剂和 不饱和烃以及膜截留抑制剂分析 通过电喷雾电离质谱法、15 N-NMR、13 C-15 N-NMR和1H- NMR和气相色谱法将鉴别特定的NO2衍生加合物。 这些研究还将确定不饱和脂肪酸的自氧化是否 脂肪酸有助于多肽失活;从而减少了 龙的防御

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.