Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD

作者：Natanek Samantha A^*; Gosker Harry R; Slot Ilse G M; Marsh Gemma S; Hopkinson Nicholas S; Moxham John; Kemp Paul R; Schols Annemie M W J; Polkey Michael I

来源：European Respiratory Journal, 2013, 41(6): 1275-1283.

DOI：10.1183/09031936.00098412

• AMP kinase
• calcineurin
• myocyte enhancer factor-2
• protein kinase A

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. %26lt;br%26gt;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)-alpha, protein kinase A-alpha 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. %26lt;br%26gt;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. %26lt;br%26gt;Reduced phospho-AMPK may contribute to reduced quadriceps oxidative capacity and endurance in COPD.

• 出版日期2013-6