Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD.

S. A. Natanek*, H.R. Gosker, I.G.M. Slot, G. S. Marsh, N.S. Hopkinson, J. Moxham, P. R. Kemp, A.M.W.J. Schols, M.I. Polkey

*Corresponding author for this work

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Abstract

Reduced quadriceps endurance in COPD is associated with a predominance of type II glycolytic over type I oxidative fibres (fibre shift, FS) and reduced muscle energy stores. 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 FS.We measured lung function, physical activity, exercise performance, quadriceps strength and endurance (non-volitionally) in 38 GOLD Stage I-IV COPD patients and 23 healthy age-matched controls. Participants had a quadriceps biopsy; type I and II fibre proportions were determined using immunohistochemistry and FS defined using published reference ranges. Calcineurin A, phosphorylated adenosine monophosphate kinase-alpha (phospho-AMPK) and protein kinase A-alpha catalytic subunits were measured by western blotting and modulators of calcineurin activity, calmodulin, 14-3-3 proteins, and myocyte-enriched calcineurin-interacting protein-1 mRNA measured by western blotting and qPCR respectively. 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 than without FS. Phospho-AMPK levels correlated with quadriceps endurance in patients.Reduced phospho-AMPK may contribute to reduced quadriceps oxidative capacity and endurance in COPD.
Original languageEnglish
Pages (from-to)1275-1283
Number of pages9
JournalEuropean Respiratory Journal
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • AMP kinase
  • calcineurin
  • myocyte enhancer factor-2
  • protein kinase A
  • OBSTRUCTIVE PULMONARY-DISEASE
  • ACTIVATED PROTEIN-KINASE
  • SKELETAL-MUSCLE
  • CALCINEURIN
  • EXERCISE
  • PHOSPHORYLATION
  • STANDARDIZATION
  • EXPRESSION
  • TRANSCRIPTION
  • PATHOLOGY

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