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Paraoxonase 1 activity and protein thiol oxidation in sera of COPD patients

Introduction: Reactive oxygen species, generated by cigarette smoke and by activated lung and peripheral blood cells, may provoke oxidative-antioxidative disbalance in patients with chronic obstructive pulmonary disease (COPD). Paraoxonase 1 (PON1) is an HDL-associated enzyme with three cysteine residues in positions 41, 284 and 353 ; C41 and C353 form a disulfide bond while C284 is free. The enzyme has both antiatherogenic and antioxidative properties. Aims and objectives: The aim of this study was to assess PON1 activity and the level of free protein thiols in sera of COPD patients, in relation to disease severity (GOLD stages) and smoking history. We hypothesized that both the activity of PON1 and the concentration of total thiols might be influenced by strong oxidative environment in COPD patients. Methods: The study was carried out on 107 clinically stable COPD patients (FEV1 = 41  14, FEV1/FVC = 62.0  10.6) and 45 healthy volunteers (FEV1 = 106  15, FEV1/FVC = 86.2  6.6). Protein thiols were measured by a spectrophotometric method using 5, 5’-dithiobis-(2-nitrobenzoic acid) (DTNB). PON1 activity was assayed by monitoring the release of p-nitrophenol from paraoxon in the absence (basal PON1 activity) or in the presence of NaCl (salt-stimulated PON1 activity). Results: PON1 activities, both basal and salt-stimulated, were significantly decreased in COPD patients compared with healthy individuals (72 (46-128) vs 90 (72-158) U/L ; 135 (86-267) vs 168 (132-316) U/L, respectively). The most pronounced reduction in both PON1 activities was shown in GOLD 2 stage (basal: 63 (46-107) U/L ; stimulated: 114 (82-219) U/L). Significant difference in protein thiols was present between COPD patients and controls (0.090  0.050 vs 0.165  0.053 mmol/L), and this reduction of free sulfhydryl groups was not dependent on disease severity. Conclusions: Significant reduction of PON1 activity and the level of protein thiols suggest a disturbed redox balance. The results obtained show that the maximum reduction in PON1 activity is detectable in moderate stage of the disease, and that some compensatory mechanisms are activated in severe stages of COPD.

chronic obstructive pulmonary disease; oxidative-antioxidative disbalance; paraoxonase 1 activity

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