Decreased Serum Sirtuin-1 in COPD

Jonathan R Baker,Andriana I Papaioannou,Stelios Loukides,Kazuhiro Ito,Anastasia Papaporfyriou,Satoru Yanagisawa,Chaitanya Vuppusetty,Peter J Barnes

doi:10.1016/j.chest.2017.05.004

Jonathan R Baker, Andriana I Papaioannou + Show 6 more

Open Access

https://doi.org/10.1016/j.chest.2017.05.004

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Abstract

BackgroundThe protein deacetylase sirtuin-1 (SIRT1) is an antiaging molecule that is decreased in the lung in patients with COPD. Recently, SIRT1 was reported to be detectable in serum, but serum SIRT1 (s120S) levels have not yet been reported in patients with COPD.MethodsSerum SIRT1 protein of all samples was measured by Western blot, and the SIRT1 protein band densities were calculated and compared with clinical parameters.ResultsSeveral molecular sizes of SIRT1, including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by Western blot. Among them, only the 120-kDa s120S was significantly decreased in patients with COPD compared with the control subjects without COPD (s120S ratio in healthy subjects = 0.90 ± 0.34 vs those with COPD = 0.68 ± 0.24; P = .014) and was positively correlated with airway obstruction (FEV1/FVC, r = 0.31; P = .020); its severity measured by FEV1 % predicted (r = 0.29; P = .029). s120S also showed a positive correlation with BMI (r = 0.36; P = .0077) and diffusing capacity of the lung per unit volume (the carbon monoxide transfer coefficient: KCO%) (r = 0.32; P = .025). It was also significantly decreased with increasing severity of lung emphysema (r = –0.40; P = .027) and with a clinical history of frequent COPD exacerbations (infrequent vs frequent, 0.76 ± 0.20 vs 0.56 ± 0.26; P = .027). SIRT1 was not detected in supernatant of A549 and primary epithelial cells in normal culture conditions.Conclusionss120S 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 biomarker for certain disease characteristics of COPD.

Highlights

RESULTSSeveral molecular sizes of SIRT1, including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by Western blot
The protein deacetylase sirtuin-1 (SIRT1) is an antiaging molecule that is decreased in the lung in patients with COPD
Only the 120-kDa s120S was significantly decreased in patients with COPD compared with the control subjects without COPD (s120S ratio in healthy subjects 1⁄4 0.90 Æ 0.34 vs those with COPD 1⁄4 0.68 Æ 0.24; P 1⁄4 .014) and was positively correlated with airway obstruction (FEV1/FVC, r 1⁄4 0.31; P 1⁄4 .020); its severity measured by FEV1 % predicted (r 1⁄4 0.29; P 1⁄4 .029). s120S showed a positive correlation with airflow obstruction (BMI) (r 1⁄4 0.36; P 1⁄4 .0077) and diffusing capacity of the lung per unit volume (r 1⁄4 0.32; P 1⁄4 .025)

Summary

RESULTS

Several molecular sizes of SIRT1, including 120 kDa (actual size) and fragments (102 and 75 kDa) were quantified by Western blot. COPD is a major global health problem.[22,23] In contrast to asthma, COPD is mainly caused by noxious gases such as cigarette smoke[24,25] and is characterized by poorly reversible small airway obstruction, emphysema, and corticosteroid-insensitive inflammation.[26] COPD progresses slowly; most patients are elderly, and there is increasing evidence that it reflects accelerated aging of the lungs.[27,28,29] SIRT1 is decreased in the peripheral lung and peripheral blood mononuclear cells in patients with COPD.[30] In this study, we measured the serum levels of SIRT1 by Western blot in patients with COPD and age-matched control subjects and examined how it relates to characteristics of the disease

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