Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease
Autor: | Gulam Haji, Coen H. Wiegman, Charalambos Michaeloudes, Mehul S. Patel, Katrina Curtis, Pankaj Bhavsar, Michael I. Polkey, Ian M. Adcock, Kian Fan Chung, on behalf of the COPDMAP consortium |
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Přispěvatelé: | Medical Research Council (MRC) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty COPDMAP consortium Respiratory System SOD2 Bronchi Oxidative phosphorylation Mitochondrion medicine.disease_cause Gastroenterology Quadriceps Muscle 03 medical and health sciences Pulmonary Disease Chronic Obstructive 0302 clinical medicine Internal medicine medicine Airways COPD Humans Respiratory system 1102 Cardiorespiratory Medicine and Haematology Aged chemistry.chemical_classification lcsh:RC705-779 Membrane Potential Mitochondrial Reactive oxygen species Lung business.industry Research 1103 Clinical Sciences lcsh:Diseases of the respiratory system Middle Aged medicine.disease respiratory tract diseases Mitochondria Oxidative Stress 030104 developmental biology medicine.anatomical_structure Quadriceps 030228 respiratory system chemistry Female business Reactive Oxygen Species Oxidative stress |
Zdroj: | Respiratory Research Respiratory Research, Vol 21, Iss 1, Pp 1-11 (2020) |
ISSN: | 1465-993X 1465-9921 |
Popis: | Background Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD. Methods Bronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function. Results Decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression. Conclusions Mitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs. |
Databáze: | OpenAIRE |
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