Increased FXYD1 and PGC-1α mRNA after blood flow-restricted running is related to fibre type-specific AMPK signalling and oxidative stress in human muscle

Aim: This study explored the effects of blood flow restriction (BFR) on mRNA responses of PGC-1α (total, 1α1, and 1α4) and Na+,K+-ATPase isoforms (NKA; α1-3, β1-3, and FXYD1) to an interval running session and determined whether these effects were related to increased oxidative stress, hypoxia, and fibre type-specific AMPK and CaMKII signalling, in human skeletal muscle. Methods: In a randomized, crossover fashion, 8 healthy men (26 ± 5 year and 57.4 ± 6.3 mL kg−1 min−1) completed 3 exercise sessions: without (CON) or with blood flow restriction (BFR), or in systemic hypoxia (HYP, ~3250 m). A muscle sample was collected before (Pre) and after exercise (+0 hour, +3 hours) to quantify mRNA, indicators of oxidative stress (HSP27 protein in type I and II fibres, and catalase and HSP70 mRNA), metabolites, and α-AMPK Thr172/α-AMPK, ACC Ser221/ACC, CaMKII Thr287/CaMKII, and PLBSer16/PLB ratios in type I and II fibres. Results: Muscle hypoxia (assessed by near-infrared spectroscopy) was matched between BFR and HYP, which was higher than CON (~90% vs ~70%; P <.05). The mRNA levels of FXYD1 and PGC-1α isoforms (1α1 and 1α4) increased in BFR only (P <.05) and were associated with increases in indicators of oxidative stress and type I fibre ACC Ser221/ACC ratio, but dissociated from muscle hypoxia, lactate, and CaMKII signalling. Conclusion: Blood flow restriction augmented exercise-induced increases in muscle FXYD1 and PGC-1α mRNA in men. This effect was related to increased oxidative stress and fibre type-dependent AMPK signalling, but unrelated to the severity of muscle hypoxia, lactate accumulation, and modulation of fibre type-specific CaMKII signalling.