Signaling Pathway Activation After Exercise in Patients With Chronic Obstructive Pulmonary Disease (SIM)

Signaling Pathway Activation in the Quadriceps of Patients With COPD After an Acute Bout of Resistance

Muscle weakness and atrophy are important consequences of chronic obstructive pulmonary disease (COPD). Although resistance exercises increase strength and muscle mass in patients with COPD, the response to training appears to be suboptimal in these individuals. A dysregulation in the signaling pathways involved in the regulation of muscle mass could play an important role in this phenomenon. Hypothesis: Proteins involved in muscle mass regulation will be less activated in the quadriceps of patients with COPD following the acute bout of resistance training exercise compared to healthy age-matched controls.

Our objective is to investigate the impact of an acute bout of resistance training on key signaling pathways involved in the regulation of muscle mass in moderate to severe COPD (FEV1 under 60% of predicted). Key proteins of signaling intramuscular pathways involved in protein synthesis and degradation will be measured before after 72 contractions of the quadriceps. The exercise protocol was designed to match the actual exercise prescription model use in the context of pulmonary rehabilitation. A squat, leg press and leg extension will be done at 80% of max with one minute rest between sets. A biopsy of the quadriceps will be done before and after exercise in order to measure phosphorylated kinases, total protein content and mRNA expressions. All our patients will undergo a thorough baseline assessment in pulmonary capacity, muscle force and body composition.

Post-exercise signaling proteins phosphorylation level in the quadriceps of COPD patients and age-matched healthy controls

Phosphorylation status of key proteins (Akt, p70, mTOR, p38, JNK, ERK) will be lesser modulated in the quadriceps of patients with COPD compare to healthy controls. The phosphorylated as well as the total protein levels will be measured by western blot. The data will be presented as arbitrary units and compared with values obtained in healthy age-matched healthy controls.

Inclusion Criteria: Male COPD with an FEV1 of under 60% of predicted non-smoker Between 50 and 75 years old Exclusion Criteria: All inflammatory disease (HIV, Cancer, renal and cardiac deficiency) Hormonal dysregulation Inferior limb pathology Neuromuscular pathology History of tabacco or alcool abuse Oxygen dependent Recent exacerbation (2 months) of the symptoms of COPD