Reduced HDAC2 in skeletal muscle of COPD patients
Abstract Background Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(...
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doaj-f5252cb083294716a3bde3ad17bf3f192020-11-25T00:47:06ZengBMCRespiratory Research1465-993X2017-05-0118111010.1186/s12931-017-0588-8Reduced HDAC2 in skeletal muscle of COPD patientsMasako To0Elisabeth B. Swallow1Kenich Akashi2Kosuke Haruki3S Amanda Natanek4Michael I. Polkey5Kazuhiro Ito6Peter J. Barnes7Airway Disease Section, National Heart and Lung Institute, Imperial CollegeNIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield Foundation Trust & Imperial CollegeAirway Disease Section, National Heart and Lung Institute, Imperial CollegeDepartment of Laboratory Medicine, Dokkyo Medical University Koshigaya HospitalNIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield Foundation Trust & Imperial CollegeNIHR Respiratory Biomedical Research Unit at the Royal Brompton and Harefield Foundation Trust & Imperial CollegeAirway Disease Section, National Heart and Lung Institute, Imperial CollegeAirway Disease Section, National Heart and Lung Institute, Imperial CollegeAbstract Background Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. Methods and results Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/β-actin: 0.59 ± 0.34) was significantly lower than that in SM (1.9 ± 1.1, p = 0.0007) and NS (1.2 ± 0.7, p = 0.029). HDAC2 protein in skeletal muscle was significantly correlated with forced expiratory volume in 1 s % predicted (FEV1 % pred) (rs = 0.53, p = 0.008) and quadriceps maximum voluntary contraction force (MVC) (rs = 0.42, p = 0.029). HDAC5 protein in muscle biopsies of COPD patients (HDAC5/β-actin: 0.44 ± 0.26) was also significantly lower than that in SM (1.29 ± 0.39, p = 0.0001) and NS (0.98 ± 0.43, p = 0.020). HDAC5 protein in muscle was significantly correlated with FEV1 % pred (rs = 0.64, p = 0.0007) but not with MVC (rs = 0.30, p = 0.180). Nuclear factor-kappa B (NF-κB) DNA binding activity in muscle biopsies of COPD patients (10.1 ± 7.4) was significantly higher than that in SM (3.9 ± 7.3, p = 0.020) and NS (1.0 ± 1.2, p = 0.004and significantly correlated with HDAC2 decrease (rs = −0.59, p = 0.003) and HDAC5 (rs = 0.050, p = 0.012). HDAC2 knockdown by RNA interference in primary skeletal muscle cells caused an increase in NF-κB activity, NF-κB acetylation and basal tumour necrosis factor (TNF)-α production, as well as progressive cell death through apoptosis. Conclusion Skeletal muscle weakness in COPD may result from HDAC2 down-regulation in skeletal muscle via acetylation and activation of NF-κB. The restoration of HDAC2 levels might be a therapeutic target for improving skeletal muscle weakness in COPD.http://link.springer.com/article/10.1186/s12931-017-0588-8COPDSkeletal muscle dysfunctionHDAC2Nuclear factor-kappa BApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masako To Elisabeth B. Swallow Kenich Akashi Kosuke Haruki S Amanda Natanek Michael I. Polkey Kazuhiro Ito Peter J. Barnes |
spellingShingle |
Masako To Elisabeth B. Swallow Kenich Akashi Kosuke Haruki S Amanda Natanek Michael I. Polkey Kazuhiro Ito Peter J. Barnes Reduced HDAC2 in skeletal muscle of COPD patients Respiratory Research COPD Skeletal muscle dysfunction HDAC2 Nuclear factor-kappa B Apoptosis |
author_facet |
Masako To Elisabeth B. Swallow Kenich Akashi Kosuke Haruki S Amanda Natanek Michael I. Polkey Kazuhiro Ito Peter J. Barnes |
author_sort |
Masako To |
title |
Reduced HDAC2 in skeletal muscle of COPD patients |
title_short |
Reduced HDAC2 in skeletal muscle of COPD patients |
title_full |
Reduced HDAC2 in skeletal muscle of COPD patients |
title_fullStr |
Reduced HDAC2 in skeletal muscle of COPD patients |
title_full_unstemmed |
Reduced HDAC2 in skeletal muscle of COPD patients |
title_sort |
reduced hdac2 in skeletal muscle of copd patients |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2017-05-01 |
description |
Abstract Background Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. Methods and results Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/β-actin: 0.59 ± 0.34) was significantly lower than that in SM (1.9 ± 1.1, p = 0.0007) and NS (1.2 ± 0.7, p = 0.029). HDAC2 protein in skeletal muscle was significantly correlated with forced expiratory volume in 1 s % predicted (FEV1 % pred) (rs = 0.53, p = 0.008) and quadriceps maximum voluntary contraction force (MVC) (rs = 0.42, p = 0.029). HDAC5 protein in muscle biopsies of COPD patients (HDAC5/β-actin: 0.44 ± 0.26) was also significantly lower than that in SM (1.29 ± 0.39, p = 0.0001) and NS (0.98 ± 0.43, p = 0.020). HDAC5 protein in muscle was significantly correlated with FEV1 % pred (rs = 0.64, p = 0.0007) but not with MVC (rs = 0.30, p = 0.180). Nuclear factor-kappa B (NF-κB) DNA binding activity in muscle biopsies of COPD patients (10.1 ± 7.4) was significantly higher than that in SM (3.9 ± 7.3, p = 0.020) and NS (1.0 ± 1.2, p = 0.004and significantly correlated with HDAC2 decrease (rs = −0.59, p = 0.003) and HDAC5 (rs = 0.050, p = 0.012). HDAC2 knockdown by RNA interference in primary skeletal muscle cells caused an increase in NF-κB activity, NF-κB acetylation and basal tumour necrosis factor (TNF)-α production, as well as progressive cell death through apoptosis. Conclusion Skeletal muscle weakness in COPD may result from HDAC2 down-regulation in skeletal muscle via acetylation and activation of NF-κB. The restoration of HDAC2 levels might be a therapeutic target for improving skeletal muscle weakness in COPD. |
topic |
COPD Skeletal muscle dysfunction HDAC2 Nuclear factor-kappa B Apoptosis |
url |
http://link.springer.com/article/10.1186/s12931-017-0588-8 |
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