Dataset Information

Decreased Serum Sirtuin-1 in COPD.

ABSTRACT:

Background

The 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.

Methods

Serum SIRT1 protein of all samples was measured by Western blot, and the SIRT1 protein band densities were calculated and compared with clinical parameters.

Results

Several 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: K_CO%) (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.

Conclusions

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 biomarker for certain disease characteristics of COPD.

SUBMITTER: Yanagisawa S

PROVIDER: S-EPMC5540026 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Decreased Serum Sirtuin-1 in COPD.

Yanagisawa Satoru S Papaioannou Andriana I AI Papaporfyriou Anastasia A Baker Jonathan R JR Vuppusetty Chaitanya C Loukides Stelios S Barnes Peter J PJ Ito Kazuhiro K

Chest 20170512 2

<h4>Background</h4>The 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.<h4>Methods</h4>Serum SIRT1 protein of all samples was measured by Western blot, and the SIRT1 protein band densities were calculated and compared with clinical parameters.<h4>Results</h4>Several molecular sizes of SIRT1, inc ...[more]

PMID: 28506610

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Project description:BACKGROUND:The class III NAD-dependent histone deacetylase (HDAC) sirtuin 1 (SIRT1) is an important regulator of senescence, aging, and inflammation. SIRT1de-acetylates chromatin histones, thereby silencing inflammatory gene transcription. We have reported increased steroid-resistant senescent pro-inflammatory CD28nullCD8+ T cells in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that SIRT1 is reduced in these cells in COPD, and that treatment with SIRT1 activators (resveratrol, curcumin) and agents preventing NAD depletion (theophylline) would upregulate SIRT1 and reduce pro-inflammatory cytokine expression in these steroid-resistant cells. METHODS:Blood was collected from n?=?10 COPD and n?=?10 aged-matched controls. Expression of CD28, SIRT1, and pro-inflammatory cytokines was determined in CD8+ and CD8- T and natural killer T (NKT)-like cells cultured in the presence of ±1?µM prednisolone, ±5?mg/L theophylline, ±1?µM curcumin, ±25?µM resveratrol, using flow cytometry and immunofluorescence. RESULTS:There was an increase in the percentage of CD28nullCD8+ T and NKT-like cells in COPD patients compared with controls. Decreased SIRT1 expression was identified in CD28nullCD8+T and NKT-like cells compared with CD28+ counterparts from both patients and controls (e.g. CD28null 11?±?3% versus CD28+ 57?±?9%). Loss of SIRT1 was associated with increased production of IFN? and TNF?, steroid resistance, and disease severity. SIRT1 expression was upregulated in the presence of all drugs and was associated with a decrease in steroid resistance and IFN? and TNF? production by CD28nullCD8+T and NKT-like cells. The presence of the SIRT1 inhibitor, EX-527 negated [by 92?±?12% (median?±?SEM)] the effect of the SIRT1 activator SRT720 on the percentage of CD8+ T cells producing IFN? and TNF?. CONCLUSIONS:Steroid resistance in pro-inflammatory CD28nullCD8+ T and NKT-like cells is associated with decreased SIRT1 expression. Treatment with prednisolone, in combination with theophylline, curcumin or resveratrol increases SIRT1 expression, restores steroid sensitivity, and inhibits pro-inflammatory cytokine production from these cells and may reduce systemic inflammation in COPD. The reviews of this paper are available via the supplemental material section.

Project description:BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009-2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009-2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.

Dataset Information

Decreased Serum Sirtuin-1 in COPD.

Background

Methods

Results

Conclusions

Publications

Decreased Serum Sirtuin-1 in COPD.

Similar Datasets

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