Abstract

Oxidative stress generates reactive species that modify proteins, deplete antioxidantABSTRACT: Oxidative stress generates reactive species that modify proteins, deplete antioxidantdefenses, and contribute to chronic obstructive pulmonary disease (COPD) and ischemic heart disease(IHD). To determine whether protein modifications differ between COPD or IHD patients and healthysubjects, we performed untargeted analysis of adducts at the Cys34 locus of human serum albumin(HSA). Biospecimens were obtained from nonsmoking participants from London, U.K., including healthysubjects (n = 20) and patients with COPD (n = 20) or IHD (n = 10). Serum samples were digested withtrypsin and analyzed by liquid chromatography-high resolution mass spectrometry. Effects of air pollutionon adduct levels were also investigated based on estimated residential exposures to PM2.5, O3 and NO2.For the 39 adducts with sufficient data, levels were essentially identical in blood samples collected fromthe same subjects on two consecutive days, consistent with the 28 day residence time of HSA. Multivariatelinear regression revealed 21 significant associations, mainly with the underlying diseases but also with airpollutionexposures (p-value < 0.05). Interestingly, most of the associations indicated that adduct levelsdecreased with the presence of disease or increased pollutant concentrations. Negative associations of COPD and IHD with the Cys34 disulfide of glutathione and two Cys34 sulfoxidations, were consistent with previous results from smoking and nonsmoking volunteers and nonsmoking women exposed to indoor combustion of coal and wood.