| Title |
2D-DIGE proteomic analysis of vastus lateralis from COPD patients with low and normal fat free mass index and healthy controls
|
|---|---|
| Published in |
Respiratory Research, May 2017
|
| DOI | 10.1186/s12931-017-0525-x |
| Pubmed ID | |
| Authors |
Ramzi Lakhdar, Ellen M. Drost, William MacNee, Ricardo Bastos, Roberto A. Rabinovich |
| Abstract |
Chronic obstructive pulmonary disease (COPD) is associated with several extra-pulmonary effects of which skeletal muscle wasting is one of the most common and contributes to reduced quality of life, increased morbidity and mortality. The molecular mechanisms leading to muscle wasting are not fully understood. Proteomic analysis of human skeletal muscle is a useful approach for gaining insight into the molecular basis for normal and pathophysiological conditions. To identify proteins involved in the process of muscle wasting in COPD, we searched differentially expressed proteins in the vastus lateralis of COPD patients with low fat free mass index (FFMI), as a surrogate of muscle mass (COPDL, n = 10) (FEV1 33 ± 4.3% predicted, FFMI 15 ± 0.2 Kg.m(-2)), in comparison to patients with COPD and normal FFMI (COPDN, n = 8) and a group of age, smoking history, and sex matched healthy controls (C, n = 9) using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology, combined with mass spectrometry (MS). The effect of silencing DOT1L protein expression on markers of cell arrest was analyzed in skeletal muscle satellite cells (HSkMSCs) in vitro and assessed by qPCR and Western blotting. A subset of 7 proteins was differentially expressed in COPDL compared to both COPDN and C. We found an increased expression of proteins associated with muscle homeostasis and protection against oxidative stress, and a decreased expression of structural muscle proteins and proteins involved in myofibrillogenesis, cell proliferation, cell cycle arrest and energy production. Among these was a decreased expression of the histone methyltransferase DOT1L. In addition, silencing of the DOT1L gene in human skeletal muscle satellite cells in vitro was significantly related to up regulation of p21 (WAF1/Cip1)/CDKN1A, a marker of cell arrest and ageing. 2D-DIGE coupled with MS identified differences in the expression of several proteins in the wasted vastus lateralis that are relevant to the disease process. Down regulation of DOT1L in the vastus lateralis of COPDL patients may mediate the muscle wasting process through up regulation of markers of cell arrest and senescence. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 40% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 35 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 23% |
| Student > Master | 7 | 20% |
| Student > Bachelor | 2 | 6% |
| Researcher | 2 | 6% |
| Professor | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 14 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 14% |
| Nursing and Health Professions | 3 | 9% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Engineering | 3 | 9% |
| Physics and Astronomy | 1 | 3% |
| Other | 3 | 9% |
| Unknown | 17 | 49% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 May 2017.
All research outputs
#14,918,049
of 25,382,440 outputs
Outputs from Respiratory Research
#1,498
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#164,791
of 324,466 outputs
Outputs of similar age from Respiratory Research
#48
of 71 outputs
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