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

Research output: Contribution to journalArticleAcademicpeer-review

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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