RT Journal Article
SR Electronic
T1 Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1275
OP 1283
DO 10.1183/09031936.00098412
VO 41
IS 6
A1 Samantha A. Natanek
A1 Harry R. Gosker
A1 Ilse G.M. Slot
A1 Gemma S. Marsh
A1 Nicholas S. Hopkinson
A1 John Moxham
A1 Paul R. Kemp
A1 Annemie M.W.J. Schols
A1 Michael I. Polkey
YR 2013
UL http://erj.ersjournals.com/content/41/6/1275.abstract
AB Reduced quadriceps endurance in chronic obstructive pulmonary disease (COPD) is associated with a predominance of type II glycolytic fibres over type I oxidative fibres (fibre shift) and reduced muscle energy stores. The molecular mechanisms responsible for this remain unknown. We hypothesised that expression of known regulators of type I fibres and energy production in quadriceps muscle would differ in COPD patients with and without fibre shift. We measured lung function, physical activity, exercise performance, quadriceps strength and endurance (nonvolitionally) in 38 Global Initiative for Chronic Obstructive Lung Disease stage I–IV COPD patients and 23 healthy age-matched controls. Participants underwent a quadriceps biopsy: type I and II fibre proportions were determined using immunohistochemistry and fibre shift defined using published reference ranges. Calcineurin A, phosphorylated AMP kinase (phospho-AMPK)-α, protein kinase A-α catalytic subunits, modulators of calcineurin activity and calmodulin, 14-3-3 proteins were measured by Western blotting, and myocyte-enriched calcineurin-interacting protein-1 mRNA measured by quantitative PCR. Downstream, nuclear myocyte enhancer factor-2 capable of DNA binding was quantified by transcription factor ELISA. Unexpectedly, calcineurin expression was higher, while phospho-AMPK was lower, in COPD patients with fibre shift compared to COPD patients without fibre shift. Phospho-AMPK levels correlated with quadriceps endurance in patients. Reduced phospho-AMPK may contribute to reduced quadriceps oxidative capacity and endurance in COPD.