Abnormal transition pore kinetics and cytochrome C release in muscle mitochondria of patients with chronic obstructive pulmonary disease.
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 (P < 0.01) 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.
Puente-Maestu
Luis
L
Servicio de Neumología, Hospital General Universitario Gregorio Marañón, Madrid, Spain. lpuente@separ.es
Pérez-Parra
José
J
Godoy
Raul
R
Moreno
Nicolás
N
Tejedor
Alberto
A
Torres
Ana
A
Lázaro
Alberto
A
Ferreira
Alicia
A
Agustí
Alvar
A
D000368:Aged; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking
D045304:Cytochromes c