Permeability transition pore kinetics, cytochrome c release in mitochondria isolated from skeletal muscle of patients with COPD
L. Puente-Maestu, F. Villar, N. Moreno, F. Gonzalez-Aragoneses, S. Caramllo, A. Tejedor, J. Garcia de Pedro, A. Agusti (Madrid, Palma de MAllorca, Spain)
Source: Annual Congress 2008 - Exercise intolerance: mechanism, intervention and assessment
Disease area: Airway diseases
Abstract Rationale: Skeletal muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD). Mitochondrion permeability transition pore (MPTP) triggers apoptosis by allowing leakage of the matrix constituents. Objective: To compare MPTP kinetics, and cytochrome c (cyto-c) release in response to calcium and reactive oxygen species (ROS) in COPD patients and controls with normal lung function. Methods: Mitochondria were isolated from biopsies of Vastus Lateralis (VL), External intercostalis (EI) and Latissimus Dorsi (LD) obtained during surgery for lung cancer in 9 patients with COPD (66±9 yrs; SD) , FEV1 66±13%) and 11 controls (64±6 yrs; FEV1 95±11%). MPTP kinetics were determined by monitoring the decrease in light scattering at 540 nm in the presence of 400 mM of Cl2 Ca, cyto-c release by ELISA. Results: In mitochondria isolated from COPD patients, as compared to controls with normal lung function: (1) MPTP kinetics were abnormal; (2) cyto-c content and release in response to ROS were increased; Conclusions: These results show that in mitochondrial isolated from three different skeletal muscles (VL, EI and LD) in patients with mild to moderate COPD, MPTP kinetics, cyto-c content and release are abnormal. These observations suggest a systemic mechanism(s) occurring early during the course of the disease and provides with a biological explanation for an increased susceptibility of skeletal muscle to cell death. Supported by Fondo de Investigaciones Sanitarias (PI052563) and Neumomadrid.
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L. Puente-Maestu, F. Villar, N. Moreno, F. Gonzalez-Aragoneses, S. Caramllo, A. Tejedor, J. Garcia de Pedro, A. Agusti (Madrid, Palma de MAllorca, Spain). Permeability transition pore kinetics, cytochrome c release in mitochondria isolated from skeletal muscle of patients with COPD. Eur Respir J 2008; 32: Suppl. 52, 412
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