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

2007 ◽  
Vol 103 (4) ◽  
pp. 1395-1401 ◽  
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.

Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

2000 ◽  
Vol 279 (4) ◽  
pp. E806-E814 ◽  
Author(s):  
Henriette Pilegaard ◽  
George A. Ordway ◽  
Bengt Saltin ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Pyruvate Dehydrogenase Kinase ◽  
Heme Oxygenase 1 ◽  
Metabolic Efficiency ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels

Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60–90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to β-actin) increased by three- to sevenfold in response to exercise, peaking after 1–2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise ( n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.

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

2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
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.

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Exercise Adaptation

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.

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

1999 ◽  
Vol 276 (2) ◽  
pp. H679-H685 ◽  
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.

Myogenic mRNA markers in young and old human skeletal muscle prior to and following sequential exercise bouts

2011 ◽  
Vol 36 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Michael D. Roberts ◽  
Vincent J. Dalbo ◽  
Kyle Sunderland ◽  
Chris Poole ◽  
Scott E. Hassell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cyclin D1 ◽  
Mrna Expression ◽  
Satellite Cell ◽  
Body Mass ◽  
Body Fat ◽  
Human Skeletal Muscle ◽  
Percent Body Fat ◽  
Vastus Lateralis Muscle ◽  
Younger Men

This study examined how multiple bouts of conventional resistance training affected the mRNA expression of transcripts and a protein associated with satellite cell activity in human skeletal muscle. Ten younger men (means ± SE; age, 21.0 ± 0.5 years; body mass, 82.3 ± 4.2 kg; height, 178.4 ± 2.2 cm; percent body fat, 15.4% ± 2.9%) and 10 older men (age, 66.4 ± 1.6 years; body mass, 94.2 ± 3.7 kg; height, 180.9 ± 2.2 cm; percent body fat, 27.4% ± 1.8%) completed 3 lower-body workouts (Monday, Wednesday, Friday; 9 sets of 10 repetitions at 80% 1 repetition maximum). Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). Real-time reverse transcription–polymerase chain reaction was performed to assess genes of interest, and muscle proliferating cell nuclear antigen (PCNA) was assessed using Western blotting. The CYCLIN D1 gene was expressed more highly in the older vs. younger men (p < 0.05), whereas the expression of all other genes and muscle PCNA were similar between age groups. MYOD mRNA expression increased at T2 (p < 0.05) and MHCEMB gene expression modestly increased (p < 0.05) at T4 relative to baseline expression values in the younger men. Baseline elevations in CYCLIN D1 mRNA expression in older persons may indicate that a compensatory expression of this transcript is occurring in an attempt to retain the muscle’s proliferative potential. Increases in MYOD and MHCEMB indicate that 1 week of conventional resistance exercise may i\ncrease myogenic activity, including satellite cell proliferation and differentiation, respectively, in younger men.

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

2009 ◽  
Vol 106 (4) ◽  
pp. 1419-1424 ◽  
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.

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

2005 ◽  
Vol 289 (1) ◽  
pp. R84-R91 ◽  
Author(s):  
Nikolai Nordsborg ◽  
Martin Thomassen ◽  
Carsten Lundby ◽  
Henriette Pilegaard ◽  
Jens Bangsbo
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Mass ◽  
Human Skeletal Muscle ◽  
Mrna Level ◽  
Venous Blood ◽  
Knee Extension ◽  
Mrna Levels ◽  
Atpase Subunit ◽  
Exercise Induced

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.

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

2004 ◽  
Vol 287 (2) ◽  
pp. R322-R327 ◽  
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.

scholarly journals Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle

2003 ◽  
Vol 95 (3) ◽  
pp. 1038-1044 ◽  
Author(s):  
Niklas Psilander ◽  
Rasmus Damsgaard ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Mrna Level ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Igf I ◽  
Mrna Content ◽  
Heavy Resistance Training

Increasing evidence suggests that the myogenic regulatory factors (MRFs) and IGF-I have important roles in the hypertrophy response observed after mechanical loading. We, therefore, hypothesized that a bout of heavy-resistance training would affect the MRF and IGF-I mRNA levels in human skeletal muscle. Six male subjects completed four sets of 6-12 repetitions on a leg press and knee extensor machine separated by 3 min. Myogenin, MRF4, MyoD, IGF-IEabc (isoforms a, b, and c) and IGF-IEbc (isoform b and c) mRNA levels were determined in the vastus lateralis muscle by RT-PCR before exercise, immediately after, and 1, 2, 6, 24, and 48 h postexercise. Myogenin, MyoD, and MRF4 mRNA levels were elevated ( P < 0.005) by 100-400% 0-24 h postexercise. IGF-IEabc mRNA content decreased ( P < 0.005) by ∼44% after 1 and 6 h of recovery. The IGF-IEbc mRNA level was unaffected. The present study shows that myogenin, MyoD, and MRF4 mRNA levels are transiently elevated in human skeletal muscle after a single bout of heavy-resistance training, supporting the idea that the MRFs may be involved in regulating hypertrophy and/or fiber-type transitions. The results also suggest that IGF-IEa expression may be downregulated at the mRNA level during the initial part of recovery from resistance exercise.

scholarly journals The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle

2015 ◽  
Vol 309 (8) ◽  
pp. L857-L871 ◽  
Author(s):  
Shelly R. H. Pecorella ◽  
Jennifer V. F. Potter ◽  
Anne D. Cherry ◽  
Dionne F. Peacher ◽  
Karen E. Welty-Wolf ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Heme Oxygenase 1 ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Mitochondrial Density ◽  
Muscle Plasticity

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity.

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