Abnormal Transition Pore Kinetics and Cytochrome C Release in Muscle Mitochondria of Patients with Chronic Obstructive Pulmonary Disease
Autor: | Raul Godoy, Alberto Lázaro, Luis Puente-Maestu, Alberto Tejedor, Ana Torres, Alvar Agusti, Alicia Ferreira, José Pérez-Parra, Nicolas Moreno |
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Rok vydání: | 2009 |
Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Clinical Biochemistry Apoptosis Mitochondrion Biology Pathogenesis Pulmonary Disease Chronic Obstructive chemistry.chemical_compound Internal medicine medicine Humans Muscle Skeletal Lung Molecular Biology Aged COPD Muscles MPTP Cytochrome c Smoking Cytochromes c Skeletal muscle Cell Biology Middle Aged medicine.disease Mitochondria Mitochondria Muscle respiratory tract diseases Kinetics Endocrinology medicine.anatomical_structure chemistry biology.protein Female |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 40:746-750 |
ISSN: | 1535-4989 1044-1549 |
Popis: | Skeletal muscle dysfunction (SMD) is frequent in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial abnormalities appear to play a role in the pathogenesis of SMD. The mitochondrion permeability transition pore (MPTP) facilitates the leakage of mitochondrial matrix constituents, such as cytochrome c (cyto-c), and triggers apoptosis, known to occur in skeletal muscle of patients with COPD. Our objective was to study MPTP kinetics and cyto-c release in skeletal muscle mitochondria of patients with COPD. Mitochondria were isolated from the vastus lateralis (VL), external intercostalis (EI), and latissimus dorsi (LD) in 11 patients with COPD (66 +/- 9 yr; FEV(1) 66 +/- 13%) and 15 smokers with normal lung function (64 +/- 6 yr; FEV(1) 95 +/- 11%) who required thoracic surgery for a localized lung neoplasm. MPTP kinetics were determined spectrophotometrically (time to reach V'max, V'max and mitochondrial swelling) and cyto-c release by enzyme-linked immunosorbent assay. MPTP kinetics and cyto-c release were abnormal in patients with COPD in the three muscles studied. In addition, V'max of VL mitochondria was significantly related (P0.01) to BMI (r = -0.75 COPD, -0.67 control) and aerobic capacity (r = -0.70 COPD, -0.60 control) for the COPD group. MPTP kinetics and cyto-c release are abnormal in skeletal and respiratory muscles of patients with moderate COPD, suggesting a systemic mechanism(s) occurring early during the course of the disease. |
Databáze: | OpenAIRE |
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