Decreased serum sirtuin-1 in chronic obstructive pulmonary disease
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Accepted version
Author(s)
Type
Journal Article
Abstract
Background: The protein deacetylase sirtuin-1 (SIRT1) is an anti-aging molecule that is decreased in the lung from patients with chronic obstructive pulmonary disease (COPD). Recently, SIRT1 was reported to be detectable in serum, but serum SIRT1 levels have not yet been reported in patients with COPD.
Methods: Serum SIRT1 was measured by Western blotting, and relative ratio of band density in samples against that of a positive control were calculated.
Results: Several molecular sizes of SIRT1, including 120kDa (actual size) and fragments (102, 75kDa) were quantified by Western blotting. Among them, only the 120kDa serum SIRT1 (s120S) was significantly decreased in the patients with COPD compared to the control subjects without COPD (s120S ratio in healthy: 0.90±0.34, vs COPD: 0.68±0.24; p=0.014), and was positively correlated with airway obstruction (FEV1/ FVC; r=0.31; p=0.020) and its severity measured by FEV1 % predicted (r=0.29; p=0.029). Serum s120S also showed a positive correlation with body mass index (BMI; r=0.36; p=0.0077) and diffusing capacity of the lung per unit volume (KCO%; r=0.32; p=0.025). It was also significantly decreased with increasing severity of lung emphysema (r=-0.40, p=0.027) and with a clinical history of frequent COPD exacerbations (infrequent: 0.76±0.20 vs frequent: 0.56±0.26; p=0.027). SIRT1 was not detected in supernatant of A549 and primary epithelial cells in normal culture condition.
Conclusions: Serum SIRT1 (s120S) was decreased in the patients with COPD, potentially as reflected by the reduced SIRT1 within cells as a result of oxidative stress, and might be a potential biomarkers for certain disease characteristics of COPD.
Methods: Serum SIRT1 was measured by Western blotting, and relative ratio of band density in samples against that of a positive control were calculated.
Results: Several molecular sizes of SIRT1, including 120kDa (actual size) and fragments (102, 75kDa) were quantified by Western blotting. Among them, only the 120kDa serum SIRT1 (s120S) was significantly decreased in the patients with COPD compared to the control subjects without COPD (s120S ratio in healthy: 0.90±0.34, vs COPD: 0.68±0.24; p=0.014), and was positively correlated with airway obstruction (FEV1/ FVC; r=0.31; p=0.020) and its severity measured by FEV1 % predicted (r=0.29; p=0.029). Serum s120S also showed a positive correlation with body mass index (BMI; r=0.36; p=0.0077) and diffusing capacity of the lung per unit volume (KCO%; r=0.32; p=0.025). It was also significantly decreased with increasing severity of lung emphysema (r=-0.40, p=0.027) and with a clinical history of frequent COPD exacerbations (infrequent: 0.76±0.20 vs frequent: 0.56±0.26; p=0.027). SIRT1 was not detected in supernatant of A549 and primary epithelial cells in normal culture condition.
Conclusions: Serum SIRT1 (s120S) was decreased in the patients with COPD, potentially as reflected by the reduced SIRT1 within cells as a result of oxidative stress, and might be a potential biomarkers for certain disease characteristics of COPD.
Date Issued
2017-05-12
Date Acceptance
2017-05-01
Citation
Chest, 2017, 152 (2), pp.343-352
ISSN
1931-3543
Publisher
Elsevier
Start Page
343
End Page
352
Journal / Book Title
Chest
Volume
152
Issue
2
Copyright Statement
© 2017 The Authors. Published by Elsevier Inc under license from the American College of Chest Physicians. The accepted manuscript is available open access under a CC-BY Attribution Licence (https://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Wellcome Trust
Grant Number
093080/Z/10/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
biomarker
COPD
emphysema
serum
sirtuin-1
OBSTRUCTIVE PULMONARY-DISEASE
DEPENDENT HISTONE DEACETYLASE
PROTEIN DEACETYLASE
OXIDATIVE STRESS
AGING PROCESS
SIRT1
CELLS
LUNG
INFLAMMATION
METABOLISM
Aged
Biomarkers
Cells, Cultured
Female
Forced Expiratory Volume
Humans
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive
Sirtuin 1
Vital Capacity
1103 Clinical Sciences
Publication Status
Published