Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

The present study tested the hypothesis that exercise with a large compared with a small active muscle mass results in a higher contraction-induced increase in Na+-K+-ATPase mRNA expression due to greater hormonal responses. Furthermore, the relative abundance of Na+-K+-ATPase subunit α1, α2, α3, α4, β1, β2, and β3 mRNA in human skeletal muscle was investigated. On two occasions, eight subjects performed one-legged knee extension exercise (L) or combined one-legged knee extension and bilateral arm cranking (AL) for 5.00, 4.25, 3.50, 2.75, and 2.00 min separated by 3 min of rest. Leg exercise power output was the same in AL and L, but heart rate at the end of each exercise interval was higher in AL compared with L. One minute after exercise, arm venous blood lactate was higher in AL than in L. A higher level of blood epinephrine and norepinephrine was evident 3 min after exercise in AL compared with L. Nevertheless, none of the exercise-induced increases in α1, α2, β1, and β3 mRNA expression levels were higher in AL compared with L. The most abundant Na+-K+-ATPase subunit at the mRNA level was β1, which was expressed 3.4 times than α2. Expression of α1, β2, and β3 was less than 5% of the α2 expression, and no reliable detection of α3 and α4 was possible. In conclusion, activation of additional muscle mass does not result in a higher exercise-induced increase in Na+-K+-ATPase subunit-specific mRNA.

Download Full-text

Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.2.h679 ◽

1999 ◽

Vol 276 (2) ◽

pp. H679-H685 ◽

Cited By ~ 104

Author(s):

Thomas Gustafsson ◽

Adrian Puntschart ◽

Lennart Kaijser ◽

Eva Jansson ◽

Carl Johan Sundberg

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Hypoxia Inducible Factor ◽

Lactate Concentration ◽

Knee Extension ◽

Vegf Mrna ◽

Exercise Induced ◽

Vegf Mrna Expression

mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1α and HIF-1β in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (∼15–20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1β by 340%, but not HIF-1α and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1α and HIF-1β mRNA. The changes in VEGF, HIF-1α, and HIF-1β mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1α and HIF-1β mRNA.

Download Full-text

Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains

Journal of Applied Physiology ◽

10.1152/japplphysiol.90660.2008 ◽

2009 ◽

Vol 106 (4) ◽

pp. 1419-1424 ◽

Cited By ~ 32

Author(s):

Maarit Lehti ◽

Riikka Kivelä ◽

Paavo Komi ◽

Jyrki Komulainen ◽

Heikki Kainulainen ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Mrna Level ◽

Ankyrin Repeat ◽

Mrna Levels ◽

Repeat Protein ◽

Ankyrin Repeat Protein ◽

Jumping Exercise ◽

Calpain 2

Eccentric exercise induced by electrostimulation increases mRNA expression of titin-complex proteins in rodent skeletal muscle. In this study, mRNA expression of titin, muscle LIM protein (MLP), cardiac ankyrin repeat protein (CARP), ankyrin repeat domain protein 2 (Ankrd2), diabetes-related ankyrin repeat protein (DARP), and calcium-activated proteinases, calpains, were investigated in human skeletal muscle after fatiguing jumping exercise. Fatiguing jumping exercise did not change mRNA expression of titin, DARP, calpain 1, or calpain 3. MLP, Ankrd2 and calpain 2 mRNA levels were increased 2 days postexercise. CARP mRNA level was already elevated 30 min and remained elevated 2 days postexercise. Increased mRNA expression of MLP, CARP, and Ankrd2, observed for the first time in human skeletal muscle, may be part of the signaling activated by physical exercise. The rapid increase in the level of CARP mRNA nominates CARP as one of the first genes to respond to exercise. The increase in the mRNA level of calpain 2 suggests its involvement in myofiber remodeling after strenuous jumping exercise.

Download Full-text

Cytokine gene expression in human skeletal muscle during concentric contraction: evidence that IL-8, like IL-6, is influenced by glycogen availability

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00030.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. R322-R327 ◽

Cited By ~ 86

Author(s):

M. H. Stanley Chan ◽

Andrew L. Carey ◽

Matthew J. Watt ◽

Mark A. Febbraio

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Venous Blood ◽

Dry Mass ◽

Cytokine Gene Expression ◽

Mrna Levels ◽

Before And After ◽

Factor Α ◽

Resting Muscle

To determine the expression and induction of cytokines in human skeletal muscle during concentric contractions, eight males performed 60 min of bicycle exercise, with either a normal (Con) or reduced (Lo Gly) preexercise intramuscular glycogen content. Muscle biopsy samples were obtained before and after exercise and analyzed for glycogen and the mRNA expression of 13 cytokines. Resting muscle glycogen was higher ( P < 0.05) in Con compared with Lo Gly and was reduced ( P < 0.05) to 102 ± 32 vs. 17 ± 5 mmol U glycosyl/kg dry mass for Con and Lo Gly, respectively. We detected mRNA levels in human skeletal muscle for five cytokines, namely interleukin (IL)-1β, IL-6, IL-8, IL-15, and tumor necrosis factor-α. However, muscle contraction increased ( P < 0.05) the mRNA expression of IL-6 and IL-8 alone. In addition, the fold change for both IL-8 and IL-6 was markedly higher ( P < 0.05) in Lo Gly compared with Con. Given these results, we analyzed venous blood samples, obtained before and during exercise, for IL-6 and IL-8. Plasma IL-6 was not different at rest, and although the circulating concentration of this cytokine increased ( P < 0.05) it increased to a greater extent ( P < 0.05) throughout exercise in Lo Gly. In contrast, plasma IL-8 was not affected by exercise or treatment. These data demonstrate that cytokines are not ubiquitously expressed in skeletal muscle and that only IL-6 and IL-8 mRNA are increased during contraction of this mode and duration. Furthermore, the mRNA abundance of IL-6 and IL-8 appears to be influenced by glycogen availability in the contracting muscle.

Download Full-text

Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00206.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. E1189-E1194 ◽

Cited By ~ 84

Author(s):

Christian P. Fischer ◽

Peter Plomgaard ◽

Anne K. Hansen ◽

Henriette Pilegaard ◽

Bengt Saltin ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Muscle Glycogen ◽

Human Skeletal Muscle ◽

Acute Exercise ◽

Glycogen Content ◽

Knee Extensor ◽

Exercise Induced ◽

Response To Exercise ◽

Resting Muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.

Download Full-text

Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

Experimental Physiology ◽

10.1113/ep087401 ◽

2019 ◽

Vol 104 (3) ◽

pp. 407-420 ◽

Cited By ~ 15

Author(s):

Hashim Islam ◽

Brittany A. Edgett ◽

Jacob T. Bonafiglia ◽

Talya Shulman ◽

Andrew Ma ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Qpcr Analysis ◽

Exercise Induced ◽

Induced Changes ◽

Technical Considerations

Download Full-text

Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00071.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. R397-R402 ◽

Cited By ~ 45

Author(s):

Lotte Jensen ◽

Henriette Pilegaard ◽

P. Darrell Neufer ◽

Ylva Hellsten

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Human Skeletal Muscle ◽

Acute Exercise ◽

Splice Variants ◽

Knee Extensor ◽

Vastus Lateralis Muscle ◽

Mrna Levels ◽

Vegf Mrna ◽

Exercise Induced

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.

Download Full-text

A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00531.2007 ◽

2007 ◽

Vol 103 (4) ◽

pp. 1395-1401 ◽

Cited By ~ 32

Author(s):

Riikka Kivelä ◽

Heikki Kyröläinen ◽

Harri Selänne ◽

Paavo V. Komi ◽

Heikki Kainulainen ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Mechanical Loading ◽

Human Skeletal Muscle ◽

Hypoxia Inducible Factor ◽

Tissue Growth ◽

Vastus Lateralis Muscle ◽

Ccn Proteins ◽

Mrna Levels ◽

Hypoxia Inducible Factor 1Α

High mechanical loading was hypothesized to induce the expression of angiogenic and/or lymphangiogenic extracellular matrix (ECM) proteins in skeletal muscle. Eight men performed a strenuous exercise protocol, which consisted of 100 unilateral maximal drop jumps followed by submaximal jumping until exhaustion. Muscle biopsies were taken 30 min and 48 h postexercise from the vastus lateralis muscle and analyzed for the following parameters: mRNA and protein expression of ECM-associated CCN proteins [cysteine-rich angiogenic protein 61 (Cyr61)/CCN1, connective tissue growth factor (CTGF)/CCN2], and mRNA expression of vascular endothelial growth factors (VEGFs) and hypoxia-inducible factor-1α. The mRNA expression of Cyr61 and CTGF increased 30 min after the exercise (14- and 2.5-fold, respectively; P < 0.001). Cyr61 remained elevated 48 h postexercise (threefold; P < 0.05). The mRNA levels of VEGF-A, VEGF-B, VEGF-C, VEGF-D, or hypoxia-inducible factor-1α did not change significantly at either 30 min or 48 h postexercise; however, the variation between subjects increased markedly in VEGF-A and VEGF-B mRNA. Cyr61 protein levels were higher at both 30 min and 48 h after the exercise compared with the control ( P < 0.05). Cyr61 and CTGF proteins were localized to muscle fibers and the surrounding ECM by immunohistochemistry. Fast fibers stained more intensively than slow fibers. In conclusion, mechanical loading induces rapid expression of CCN proteins in human skeletal muscle. This may be one of the early mechanisms involved in skeletal muscle remodeling after exercise, since Cyr61 and CTGF regulate the expression of genes involved in angiogenesis and ECM remodeling.

Download Full-text