NO2 DERIVED POLYPEPTIDE ADDUCTS

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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.