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
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