Eccentric exercise markedly increases c-Jun NH2-terminal kinase activity in human skeletal muscle

1999 ◽  
Vol 87 (5) ◽  
pp. 1668-1673 ◽  
Author(s):  
Marni D. Boppart ◽  
Doron Aronson ◽  
Lindsay Gibson ◽  
Ronenn Roubenoff ◽  
Leslie W. Abad ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Eccentric Exercise ◽  
Intracellular Signaling ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Fold Increase ◽  
Mitogen Activated Protein Kinase ◽  
Eccentric Contractions ◽  
Vastus Lateralis Muscle

Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 ± 4.5 vs. 3.5 ± 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle.

Subcellular fractionation reveals HSP72 does not associate with SERCA in human skeletal muscle following damaging eccentric and concentric exercise

2014 ◽  
Vol 116 (11) ◽  
pp. 1503-1511 ◽  
Author(s):  
Noni T. Frankenberg ◽  
Graham D. Lamb ◽  
Kristian Vissing ◽  
Robyn M. Murphy
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Human Skeletal Muscle ◽  
Physiological Stress ◽  
Vastus Lateralis ◽  
Tight Binding ◽  
Fold Increase ◽  
Subcellular Fractionation ◽  
Vastus Lateralis Muscle ◽  
Type I

Through its upregulation and/or translocation, heat shock protein 72 (HSP72) is involved in protection and repair of key proteins after physiological stress. In human skeletal muscle we investigated HSP72 protein after eccentric (ECC1) and concentric (CONC) exercise and repeated eccentric exercise (ECC2; 8 wk later) and whether it translocated from its normal cytosolic location to membranes/myofibrils. HSP72 protein increased ∼2-fold 24 h after ECC1, with no apparent change after CONC or ECC2. In resting (nonstressed) human skeletal muscle the total pool of HSP72 protein was present almost exclusively in the cytosolic fraction, and after each exercise protocol the distribution of HSP72 protein remained unaltered. Overall, the amount of HSP72 protein in the cytosol increased 24 h after ECC1, matching the fold increase that was measured in total HSP72 protein. To better ascertain the capabilities and limitations of HSP72, using quantitative Western blotting we determined the HSP72 protein content to be 11.4 μmol/kg wet weight in resting human vastus lateralis muscle, which is comprised of Type I (slow-twitch) and Type II (fast-twitch) fibers. HSP72 protein content was similar in individual Type I or II fiber segments. After physiological stress, HSP72 content can increase and, although the functional consequences of increased amounts of HSP72 protein are poorly understood, it has been shown to bind to and protect protein pumps like SERCA and Na+-K+-ATPase. Given no translocation of cytosolic HSP72, these findings suggest eccentric contractions, unlike other forms of stress such as heat, do not trigger tight binding of HSP72 to its primary membrane-bound target proteins, in particular SERCA.

Molecular responses of human muscle to eccentric exercise

2003 ◽  
Vol 95 (6) ◽  
pp. 2485-2494 ◽  
Author(s):  
Yi-Wen Chen ◽  
Monica J. Hubal ◽  
Eric P. Hoffman ◽  
Paul D. Thompson ◽  
Priscilla M. Clarkson
Keyword(s):  
Skeletal Muscle ◽  
Eccentric Exercise ◽  
Inflammatory Responses ◽  
Vastus Lateralis ◽  
Transcriptional Response ◽  
Eccentric Contractions ◽  
Vastus Lateralis Muscle ◽  
Tenascin C ◽  
Chemokine Ligand ◽  
High Concordance

We examined the effect of eccentric exercise on the transcriptome of skeletal muscle in three male human volunteers who performed 300 concentric contractions with one leg and 300 eccentric contractions with the opposite leg. Vastus lateralis muscle biopsies were taken from both legs at 4–8 h after exercise, and expression was profiled by using 12,000 gene Affymetrix U95Av2 microarrays. We found a high concordance of expression responses to eccentric contractions between our human and rat data from a previous study (Chen YW, Nader GA, Baar KR, Fedele MJ, Hoffman EP, and Esser KA. J Physiol 545: 27–41, 2002) (∼50% of gene expression changes shared between species). Potential human-specific changes included greater inflammatory responses [chemokine (C-C motif) ligand 2, C/EBP delta, and IL-1 receptor] and vascular remodeling (tenascin C and lipocortin II). Induction of c- fos and lipocortin II were confirmed at the protein level, with c- fos localized to myofiber nuclei and lipocortin II to intramuscular capillaries. We also confirmed the eccentric-induced expression of six transcripts by quantitative RT-PCR (cardiac ankyrin-repeated protein, chemokine ligand 2, CCAAT/enhancer binding protein delta, IL-1 receptor, tenascin C, and cysteine-rich angiogenic inducer 61). These data provide the first characterization of the transcriptional response of skeletal muscle to eccentric exercise in humans and represent a preliminary step in understanding the molecular processes underlying muscle remodeling (including a new focus on rapid changes in the capillary bed) and inflammatory responses after damaging lengthening contractions.

scholarly journals Training state and skeletal muscle autophagy in response to 36 h of fasting

2018 ◽  
Vol 125 (5) ◽  
pp. 1609-1619 ◽  
Author(s):  
Maja Munk Dethlefsen ◽  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Tomasz Stankiewicz ◽  
Jens Bangsbo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Kinase ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Adaptor Protein ◽  
Vastus Lateralis Muscle ◽  
Trained Subjects ◽  
Lateralis Muscle ◽  
Training State

The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced ( P < 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT)Thr308, AMP-activated protein kinase (AMPK)Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1)Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1Ser757 phosphorylation, was lower ( P < 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher ( P < 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

scholarly journals Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise

2009 ◽  
Vol 107 (5) ◽  
pp. 1600-1611 ◽  
Author(s):  
U. R. Mikkelsen ◽  
H. Langberg ◽  
I. C. Helmark ◽  
D. Skovgaard ◽  
L. L. Andersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Eccentric Exercise ◽  
Satellite Cells ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Cell Activity ◽  
Inflammatory Cells ◽  
Vastus Lateralis Muscle

Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working as a control (unblocked leg). Muscle biopsies were collected before and 8 days after exercise. Changes in satellite cells and inflammatory cell numbers were investigated by immunohistochemistry. Satellite cells were identified using antibodies against neural cell adhesion molecule and Pax7. The number of Pax7+cells per myofiber was increased by 96% on day 8 after exercise in the unblocked leg (0.14 ± 0.04, mean ± SE) compared with the prevalue (0.07 ± 0.02, P < 0.05), whereas the number of Pax7+cells was unchanged in the leg muscles exposed to the NSAID (0.07 ± 0.01). The number of inflammatory cells (CD68+or CD16+cells) was not significantly increased in either of the legs 8 days after exercise and was unaffected by the NSAID. The main finding in the present study was that the NSAID infusion for 7.5 h during the exercise day suppressed the exercise-induced increase in the number of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.

Phosphorylase a in human skeletal muscle during exercise and electrical stimulation

1978 ◽  
Vol 45 (6) ◽  
pp. 852-857 ◽  
Author(s):  
P. D. Gollnick ◽  
J. Karlsson ◽  
K. Piehl ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Muscular Activity ◽  
Voluntary Exercise ◽  
Vastus Lateralis Muscle ◽  
Minor Importance ◽  
Muscle Lactate ◽  
Needle Technique

Experiments were conducted to examine the conversions of phosphorylase b to phosphorylase a in human skeletal muscle during bicycle exercise or isometric contractions. Muscle biopsies were obtained from the vastus lateralis with the needle technique at rest and either during or immediately after activity and frozen in liquid nitrogen within 2--4 s. Total phosphorylase and phosphorylase a activities were differentiated by measurement in the presence and absence of AMP, respectively. At rest 8.5% of the total phosphorylase activity existed in the a form. Little or no change in the percent of phosphorylase in the a form occurred during voluntary dynamic or static muscular activity that produced muscle lactate concentrations in excess of 18 mmol.kg-1 wet muscle. Electrical stimulation of the vastus lateralis muscle also failed to produce an increase in the percentage of phosphorylase a. These data suggest that during exercise the conversion of phosphorylase to the a form is of minor importance. An increased activity of phosphorylase b due to changes in muscle concentrations of ATP, AMP, and inorganic phosphate may regulate glycogenolysis during voluntary exercise in man.

scholarly journals Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle

2019 ◽  
Vol 316 (4) ◽  
pp. E605-E614 ◽  
Author(s):  
Daniil V. Popov ◽  
Pavel A. Makhnovskii ◽  
Elena I. Shagimardanova ◽  
Guzel R. Gazizova ◽  
Evgeny A. Lysenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Contractile Activity ◽  
Vastus Lateralis ◽  
Aerobic Exercise Training ◽  
Vastus Lateralis Muscle ◽  
Transcriptome Response ◽  
The One

Reduction in daily activity leads to dramatic metabolic disorders, while regular aerobic exercise training is effective for preventing this problem. The purpose of this study was to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness. Transcriptome changes after the one-legged knee extension exercise in exercised and contralateral nonexercised vastus lateralis muscle of seven men were evaluated by RNA-seq. Transcriptome change at baseline after 2 mo of aerobic training (5/wk, 1 h/day) was evaluated as well. Postexercise changes in the transcriptome of exercised muscle were associated with different factors, including circadian oscillations. To reveal transcriptome response specific for endurance-like contractile activity, differentially expressed genes between exercised and nonexercised muscle were evaluated at 1 and 4 h after the one-legged exercise. The contractile activity-specific transcriptome responses were associated only with an increase in gene expression and were regulated mainly by CREB/ATF/AP1-, MYC/MAX-, and E2F-related transcription factors. Endurance training-induced changes (an increase or decrease) in the transcriptome at baseline were more pronounced than transcriptome responses specific for acute contractile activity. Changes after training were associated with widely different biological processes than those after acute exercise and were regulated by different transcription factors (IRF- and STAT-related factors). In conclusion, adaptation to regular exercise is associated not only with a transient (over several hours) increase in expression of many contractile activity-specific genes, but also with a pronounced change (an increase or decrease) in expression of a large number of genes under baseline conditions.

Effect of exercise on insulin action in human skeletal muscle

1989 ◽  
Vol 66 (2) ◽  
pp. 876-885 ◽  
Author(s):  
E. A. Richter ◽  
K. J. Mikines ◽  
H. Galbo ◽  
B. Kiens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Femoral Vein ◽  
Glycogen Synthesis ◽  
Vastus Lateralis Muscle ◽  
Glycogen Concentration ◽  
Local Contraction

The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2 consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp even though indirect estimates indicated net glycogen synthesis. In contrast, in exercised muscle estimated and biopsy-verified increases in muscle glycogen concentration agreed. Local contraction-induced increases in insulin sensitivity and responsiveness play an important role in postexercise recovery of human skeletal muscle.

Human skeletal muscle malonyl-CoA at rest and during prolonged submaximal exercise

1996 ◽  
Vol 270 (3) ◽  
pp. E541-E544 ◽  
Author(s):  
L. M. Odland ◽  
G. J. Heigenhauser ◽  
G. D. Lopaschuk ◽  
L. L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
High Performance ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Submaximal Exercise ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Malonyl Coa

Previous literature has indicated that contraction-induced decreases in malonyl-CoA are instrumental in the regulation of fatty acid oxidation during prolonged submaximal exercise. This study was designed to measure malonyl-CoA in human vastus lateralis muscle at rest and during submaximal exercise. Eight males and one female cycled for 70 min (10 min at 40% and 60 min at 65% maximal O2 uptake). Needle biopsies were obtained at rest and at 10 min, 20 min, and 70 min of exercise. Malonyl-CoA content in preexercise biopsy samples determined by high-performance liquid chromatography (HPLC) was 1.53 +/- 0.18 micromol/kg dry mass (dm). Malonyl-CoA content did not change significantly during exercise (1.39 +/- 0.21 at 10 min, 1.46 +/- 0.14 at 20 min, and 1.22 +/- 0.15 micromol/kg dm at 70 min). In contrast, malonyl-CoA content determined by HPLC in perfused rat red gastrocnemius muscle decreased significantly during 20 min of stimulation at 0.7 Hz [3.44 +/- 0.54 to 1.64 +/- 0.23 nmol/g dm, (n=9)]. We conclude that human skeletal muscle malonyl-CoA content 1) is less than reported in rat skeletal muscle at rest, 2) does not decrease with prolonged submaximal exercise, and 3) is not predictive of increased fatty acid oxidation during exercise.

Thermogenesis in human skeletal muscle as measured by direct microcalorimetry and muscle contractile performance during β-adrenoceptor blockade

1986 ◽  
Vol 70 (5) ◽  
pp. 435-441 ◽  
Author(s):  
Birger Fagher ◽  
Hans Liedholm ◽  
Mario Monti ◽  
Ulrich Moritz
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Dynamic Strength ◽  
Peak Torque ◽  
Vastus Lateralis Muscle ◽  
Low Grade ◽  
Double Blind ◽  
Blind Test ◽  
Direct Calorimetry

1. The influence of β-adrenoceptor-blockade on skeletal muscle was studied in ten healthy males with propranolol, atenolol and pindolol randomly given for 8 days each in a cross-over double blind test. After 7 days on each drug, muscle function was tested by an isokinetic dynamometer. Thermogenesis in biopsy samples taken from vastus lateralis muscle after a low grade exercise was studied after 8 days on each drug by direct calorimetry with a perfusion microcalorimeter. 2. Before drug administration, a median heat production rate of 0.67 mW/g of muscle was measured. This value was significantly reduced by 25% during propranolol, but no significant change was found during atenolol or pindolol administration. 3. Peak torque decline during isokinetic endurance test changed significantly in knee flexor but not in extensor muscles, from 15% to 27% after propranolol and from 15% to 23% after pindolol. Maximum dynamic strength was unaltered. 4. Our data suggest that blockade of sympathetic β2-receptors decreases thermogenesis in human skeletal muscle and impairs isokinetic endurance.

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.

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