Biology subjects

Christiansen, D.

Publications and source records attributed to Christiansen, D..

4 recordsLinked to original sources

bioRxiv2018

Cycling with blood flow restriction improves performance and muscle K+ regulation and blunts the effect of antioxidant infusion in humans

We examined if blood flow restriction (BFR) would augment training-induced improvements in muscle K+ handling and performance during intense exercise in men, and if these adaptations would be associated with an effect of muscle antioxidant function on thigh K+ release and with fibre type-dependent modulation of Na+,K+-ATPase-isoform abundance and FXYD1 phosphorylation. Ten recreationally-active men (25 {+/-} 4 y, 49.7 {+/-} 5.3 mL*kg-1*min-1) performed 6 weeks of interval cycling, where one leg trained without (control; CON-leg) and the other leg with BFR (BFR-leg, pressure: 178 mmHg). Before and after training, catheters were inserted into the femoral artery and vein, and blood flow was assessed during single-leg knee-extensions at 25% (Ex1) and 90% of leg peak aerobic power (Ex2) with intravenous infusion of N-acetylcysteine (NAC) or saline (placebo), and a resting muscle biopsy was collected. After training, performance during exhaustive exercise increased to a greater extent in BFR-leg (23%) than in CON-leg (12%, p<0.05), whereas thigh K+ release during Ex2 was attenuated in BFR-leg only (p<0.05). Before training, NAC depressed K+ release during Ex1 (p<0.05), but not during Ex2 (p>0.05). After training, this effect was blunted in BFR-leg (p<0.05), whilst the abundance of Na+,K+-ATPase-isoform 1 in type-II (51%), {beta}1 in type-I (33%), and FXYD1 in type-I (108%) and type-II (60%) fibres was higher in BFR-leg (p<0.05; vs. CON-leg). Thus, interval training with BFR elicits greater improvements in performance and reduces muscle net K+ release during intense exercise, which may be caused by elevated ROS scavenging and fibre type-dependent increases in Na+,K+-ATPase-isoform abundance.\n\nKey pointsO_LIHere, we provide evidence that reactive oxygen species (ROS) play a role in regulating K+ homeostasis in the untrained musculature of humans, as indicated by attenuated thigh K+ efflux during exercise with concomitant antioxidant infusion.\nC_LIO_LIWe also demonstrate that interval training with blood flow restriction (BFR) augments improvements in performance and reduces K+ release from contracting muscles during intense exercise\nC_LIO_LIThe effect of training with BFR on muscle K+ handling appears to be partly mediated by increasing the protection against ROS, since the effect of antioxidant infusion was blunted after training with restricted blood flow.\nC_LIO_LIFurther, training with BFR resulted in higher abundance of Na+,K+-ATPase-isoform 1 in type-II (51%), {beta}1 in type-I (33%), and FXYD1 in type-I (108%) and type-II (60%) muscle fibres. This suggests fibre type-specific adaptations in Na+,K+-ATPase-isoform content are also important for improvements in muscle K+ handling by training with BFR in humans.\nC_LI

physiology↗

bioRxiv2017

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

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

physiology↗

bioRxiv2017

Regulation of Na+,K+-ATPase isoforms and phospholemman (FXYD1) in skeletal muscle fibre types by exercise training and cold-water immersion in men

Little is understood about the fibre type-dependent regulation of Na+,K+-ATPase (NKA) isoforms by exercise training in humans. The main aim of this study was therefore to assess the impact of a period of repeated exercise sessions on NKA-isoform protein abundance in different skeletal muscle fibre types in men. Post-exercise cold-water immersion (CWI) has been reported to increase oxidative stress, which may be one mechanism underlying increases in NKA-isoform expression. Thus, a second aim was to evaluate the effect of CWI on training-induced modulation of NKA-isoform abundance. Vastus lateralis muscle biopsies were obtained from nineteen men at rest before (Pre) and after (Post) six weeks of intense interval cycling, with training sessions followed by passive rest (CON, n=7) or CWI (10{degrees}C; COLD, n=5). Training increased (p<0.05) the abundance of NKA1 and NKA{beta}3 in both type I and type II fibres, NKA{beta}1 in type II fibres, but was without effect on NKA2 and NKA3 (p>0.05). Furthermore, training decreased FXYD1 protein content in type I fibres, which abolished its fibre type-specific expression detected at Pre (p<0.05). CWI was without impact on the responses to training (p>0.05). These results highlight that NKA isoforms are regulated in a fibre type-dependent fashion in response to intense training in humans. This may partly explain the improvement in muscle Na+/K+ handling after a period of intense training. CWI may be performed without adversely or favourably affecting training-induced changes in NKA-isoform abundance.\n\nSummary in key pointsO_LIIt is unclear how Na+,K+-ATPase (NKA) isoforms are regulated in different skeletal muscle fibre types by exercise training in humans, and the effect on phospholemman (FXYD1) protein abundance in different fibre types remains to be elucidated. We investigated the impact of six weeks of training on NKA-isoform protein abundance (1-3, {beta}1-3 and FXYD1) in type I and II muscle fibres in men.\nC_LIO_LIWe show that intense interval training selectively increases the protein content of NKA 1 and {beta}3 in both fibre types, {beta}1 in type II fibres, and decreases FXYD1 in type I fibres.\nC_LIO_LIThese results suggest the favourable impact of intense training on human muscle Na+/K+ regulation could be attributable, in part, to fibre type-dependent modulation of NKA-isoform abundance.\nC_LIO_LIGiven that cold exposure has been shown to modulate cellular redox state, which has been linked to increased NKA expression, we also investigated the effect of exercise training plus cold-water immersion (CWI) on the fibre type-specific responses of NKA isoforms and FXYD1. We found that CWI was without effect on the responses to training.\nC_LI\n\nAbbreviationsAMPK{beta}2, 5 AMP-activated protein kinase subunit {beta}2; CaMKII, Ca2+-calmodulin-dependent protein kinase isoform 2; COLD, cold-water immersion group; CON, control group; Ct, cycle threshold; CV, coefficient of variation; CWI, cold-water immersion; EDL, extensor digitorum longus; FXYD1, phospholemman isoform 1; HSP70, heat-shock protein 70; GXT, graded exercise test; K+, potassium; Km, Michaelis-Menten constant; MHC, myosin heavy chain; Na+, sodium; NF-1, neurofibromatosis type 1; NKA, Na+,K+-ATPase; ROS, reactive oxygen species; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis; SERCA1, sarco/endoplasmic reticulum Ca2+-ATPase isoform 1; VO2peak, maximum oxygen uptake.

physiology↗

bioRxiv2017

Post-exercise cold-water immersion increases Na+,K+-ATPase α2-isoform mRNA content in parallel with elevated Sp1 expression in human skeletal muscle

We investigated the effect of a session of sprint-interval exercise on the mRNA content of NKA isoforms (1-3, {beta}1-3) and FXYD1 in human skeletal muscle. To explore some of the cellular stressors involved in this regulation, we evaluated the association between these mRNA responses and those of the transcription factors Sp1, Sp3 and HIF-1. Given cold exposure perturbs muscle redox homeostasis, which may be one mechanism important for increases in NKA-isoform mRNA, we also explored the effect of post-exercise cold-water immersion (CWI) on the mRNA responses. Muscle was sampled from nineteen men before (Pre) and after (+0h, +3h) exercise plus passive rest (CON, n=10) or CWI (10{degrees}C; COLD, n=9). In COLD, exercise increased NKA2 and Sp1 mRNA (+0h, p<0.05). These genes remained unchanged in CON (p>0.05). In both conditions, exercise increased NKA1, NKA{beta}3 and HIF-1 mRNA (+3h; p <0.05), decreased NKA{beta}2 mRNA (+3h; p<0.05), whereas NKA3, NKA{beta}1, FXYD1 and Sp3 mRNA remained unchanged (p>0.05). These human findings highlight 1) sprint-interval exercise increases the mRNA content of NKA 1 and {beta}3, and decreases that of NKA {beta}2, which may relate, in part, to exercise-induced muscle hypoxia, and 2) post-exercise CWI augments NKA2 mRNA, which may be associated with promoted Sp1 activation.

physiology↗