Abstract |
Chronic obstructive pulmonary disease ( COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers ( citrate synthase, β-hydroxyacyl- CoA dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC-1α, PPAR-α, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF-α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochondrial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF-α stimulation. TNF-α also reduced mitochondrial respiration in a nuclear factor kappaB (NF-κB) -dependent manner. Importantly, TNF-α-induced NF-κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochondrial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF-α impairs muscle oxphen in a NF-κB-dependent manner.
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Authors | A H V Remels, H R Gosker, P Schrauwen, P P H Hommelberg, P Sliwinski, M Polkey, J Galdiz, E F M Wouters, R C J Langen, A M W J Schols |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 24
Issue 12
Pg. 5052-62
(Dec 2010)
ISSN: 1530-6860 [Electronic] United States |
PMID | 20807714
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- Heat-Shock Proteins
- Mitochondrial Proteins
- NF-kappa B
- PPAR alpha
- PPARGC1A protein, human
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- TFAM protein, human
- Transcription Factors
- Tumor Necrosis Factor-alpha
- Electron Transport Complex IV
- Citrate (si)-Synthase
- D-3-hydroxyacyl CoA dehydratase
- Hydro-Lyases
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Topics |
- Animals
- Blotting, Western
- Cachexia
(metabolism)
- Cell Line
- Citrate (si)-Synthase
(metabolism)
- DNA-Binding Proteins
(metabolism)
- Electron Transport Complex IV
(metabolism)
- Electrophoretic Mobility Shift Assay
- Enzyme-Linked Immunosorbent Assay
- Heat-Shock Proteins
(metabolism)
- Humans
- Hydro-Lyases
(metabolism)
- Mice
- Mitochondrial Proteins
(metabolism)
- Muscle, Skeletal
(drug effects, metabolism)
- NF-kappa B
(genetics, metabolism)
- PPAR alpha
(metabolism)
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Pulmonary Disease, Chronic Obstructive
(metabolism)
- Transcription Factors
(metabolism)
- Tumor Necrosis Factor-alpha
(genetics, metabolism, pharmacology)
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