SIRT1 Activity in Peripheral Blood Mononuclear Cells Correlates with Altered Lung Function in Patients with Chronic Obstructive Pulmonary Disease.

Valeria Conti,Carolina Vitale,Carmine Selleri,Luigi Marino,Amelia Filippelli,Damiano Capaccio,Graziamaria Corbi,Angelantonio Maglio,Alessandro Vatrella,Valentina Manzo,Roberta Cotugno,Cristiana Stellato,Paola Malangone

doi:10.1155/2018/9391261

Abstract

Background Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases [1]
Our study shows for the first time that levels of Sirtuin 1 (SIRT1) activity are decreased in peripheral blood mononuclear cells (PBMCs) of patients with chronic obstructive pulmonary disease (COPD), while remaining comparable between nonsmoking and smoking control groups; instead, SIRT1 protein expression levels were not discriminative for diseased subjects, as they were already significantly decreased in smoker versus nonsmoker controls and becoming further reduced in COPD samples
Along with decreased SIRT1 activity levels, in the COPD patients, we found an increase of systemic oxidative stress index (TOS/Trolox equivalent antioxidant capacity (TEAC) ratio) compared to control groups

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases [1]. It has been suggested that COPD is the phenotypic expression of an accelerated aging process of the lung caused, at least in part, by decreased efficiency of several antiaging molecules, including those regulating cellular redox state and oxidative stress response [7, 8]. Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD

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