Repeated-ischaemic exercise enhances mitochondrial and ion transport gene adaptations in human skeletal muscle: Role of muscle redox state and AMPK

Abstract

This study assessed the effect of repeated-ischaemic exercise on the mRNA content of PGC-1 (total, 11, and 14) and Na+,K+-ATPase (NKA; 1-3, {beta}1-3, and FXYD1) isoforms in human skeletal muscle, and studied some of the potential molecular mechanisms involved. Eight trained men (26 {+/-} 5 y and 57.4 {+/-} 6.3 mL{middle dot}kg-1{middle dot}min-1) completed three interval running sessions with (ISC) or without ischaemia (CON), or in hypoxia (HYP, ~3250 m), in a randomised, crossover fashion separated by 1 week. A muscle sample was collected from the dominant leg before (Pre) and after exercise (+0h, +3h) in all sessions to measure the mRNA content of PGC-1 and NKA isoforms, oxidative stress markers (i.e. catalase and HSP70 mRNA), muscle lactate, and phosphorylation of AMPK, ACC, CaMKII, and PLB protein in type I and II fibres. Muscle hypoxia (i.e. deoxygenated haemoglobin) was matched between ISC and HYP, which was higher than in CON (~90% vs. ~70%; p< 0.05). The levels of PGC-1 total, -11, -14, and FXYD1 mRNA increased in ISC only (p< 0.05). These changes were associated with increases in oxidative stress markers and higher p-ACCSer221/ACC in type I fibres, but were unrelated to muscle hypoxia, lactate, and CaMKII and PLB phosphorylation. These findings highlight that repeated-ischaemic exercise augments the skeletal muscle gene response related to mitochondrial biogenesis and ion transport in trained men. This effect seems attributable, in part, to increased oxidative stress and AMPK activation, whereas it appears unrelated to altered CaMKII signalling, and the muscle hypoxia and lactate accumulation induced by ischaemia.\n\nSummary in key pointsO_LIWe investigated if ischaemia would augment the exercise-induced mRNA response of PGC-1 and Na+,K+-ATPase (NKA) isoforms (1-3, {beta}1-3, and FXYD1), and examined whether this effect could be related to oxidative stress and fibre type-dependent AMPK and CaMKII signalling in the skeletal muscle of trained men.\nC_LIO_LIRepeated-ischaemic exercise increased the mRNA content of PGC-1 total, -11, and-14, and of the NKA regulatory subunit FXYD1, whereas exercise in systemic hypoxia or alone was without effect on these genes.\nC_LIO_LIThese responses to ischaemia were complemented by increased oxidative stress (as assessed by catalase and HSP70 mRNA) and ACC phosphorylation (an indicator of AMPK activation) in type I fibres. However, they were unrelated to CaMKII signalling, muscle hypoxia, and lactate accumulation.\nC_LIO_LIThus, repeated ischaemic exercise augments the muscle gene response associated with mitochondrial biogenesis and ion homeostasis in trained men. This effect seems partly attributable to promoted oxidative stress and AMPK activation.\nC_LI\n\nAbbreviations