Rumora Lada, Rajković Marija Grdić, Kopčinović Lara Milevoj, Pancirov Dolores, Čepelak Ivana, Grubišić Tihana Žanić
1Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb , Croatia.
COPD. 2014 Sep;11(5):539-45. doi: 10.3109/15412555.2014.898028. Epub 2014 May 15.
Paraoxonase 1 (PON1) is an antioxidative enzyme manly associated with high density lipoproteins (HDL) in the peripheral blood. The aim of this study was to determine the PON1 paraoxonase and arylesterase activities in patients with chronic obstructive pulmonary disease (COPD). We also aimed to determine the concentration of reduced thiol groups as a marker of protein oxidation.
The study included 105 patients with stable COPD and 44 healthy controls. PON1 activities and thiols concentration were assayed in sera by spectrophotometry.
PON1 basal (POX) and salt-stimulated paraoxonase activity (POX1) as well as arylesterase activity (ARE) were significantly reduced in COPD patients. In addition, concentration of reduced thiol groups was significantly decreased in COPD group. PON1 activities were similar in patients with different disease severity (GOLD stages). However, a significant reduction in POX, POX1 and ARE was observed already in GOLD II stage when compared to controls. POX and POX1 showed modest while ARE yielded very good power for discrimination between healthy subjects and COPD patients. Univariate and multivariate logistic regression analysis indicated that ARE is a good COPD predictor.
Reduction of PON1 activity observed in COPD patients could be partly caused by oxidative environment. Lower concentrations of reduced thiol groups in COPD patients suggest that a decrease in PON1 activity could reflect oxidative changes of enzyme free cysteine residues. Furthermore, decreased PON1 arylesterase activity might indicate a down-regulation of PON1 concentration. Our results suggest that ARE could be considered as potential biomarker for COPD diagnosis.
对氧磷酶1(PON1)是一种抗氧化酶,主要与外周血中的高密度脂蛋白(HDL)相关。本研究的目的是测定慢性阻塞性肺疾病(COPD)患者的PON1对氧磷酶和芳基酯酶活性。我们还旨在测定还原巯基的浓度,作为蛋白质氧化的标志物。
该研究纳入了105例稳定期COPD患者和44例健康对照者。通过分光光度法测定血清中的PON1活性和巯基浓度。
COPD患者的PON1基础(POX)和盐刺激的对氧磷酶活性(POX1)以及芳基酯酶活性(ARE)显著降低。此外,COPD组还原巯基的浓度显著降低。不同疾病严重程度(GOLD分期)患者的PON1活性相似。然而,与对照组相比,在GOLD II期就观察到POX、POX1和ARE显著降低。POX和POX1显示出中等的区分能力,而ARE对健康受试者和COPD患者的区分能力非常好。单因素和多因素逻辑回归分析表明,ARE是COPD的良好预测指标。
COPD患者中观察到的PON1活性降低可能部分是由氧化环境引起的。COPD患者中还原巯基浓度较低表明,PON1活性降低可能反映了酶游离半胱氨酸残基的氧化变化。此外,PON1芳基酯酶活性降低可能表明PON1浓度下调。我们的结果表明,ARE可被视为COPD诊断的潜在生物标志物。