A single bout of exercise activates matrix metalloproteinase in human skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2346-2351 ◽  
Author(s):  
E. Rullman ◽  
H. Rundqvist ◽  
D. Wågsäter ◽  
H. Fischer ◽  
P. Eriksson ◽  
...  

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.

2004 ◽  
Vol 287 (1) ◽  
pp. E8-E15 ◽  
Author(s):  
Aidar R. Gosmanov ◽  
Guillermo E. Umpierrez ◽  
Ana H. Karabell ◽  
Ruben Cuervo ◽  
Donald B. Thomason

Although a pharmacological dose of insulin produces a dramatic increase in phosphorylation and activity of Akt isoforms 1 and 2 in mammalian skeletal muscle, few studies have examined the effect of physiological concentrations of insulin on the phosphorylation of Akt-1 and -2 in normal and diabetic tissue. This study examined the patterns of insulin-stimulated Akt isoform phosphorylation and protein expression in muscle biopsies obtained from obese patients with atypical diabetes immediately after a hyperglycemic crisis and again after near-normoglycemic remission. In obese patients with new-onset diabetes mellitus presenting with hyperglycemic crisis (plasma glucose 30.5 ± 4.8 mM), in vitro stimulation of vastus lateralis muscle biopsies with 100 μU/ml (0.6 nM) insulin increased insulin receptor phosphorylation threefold and Akt-1 phosphorylation on Ser473 twofold, whereas Akt-2 phosphorylation was not stimulated. After 10-wk intensive insulin therapy that led to near-normoglycemic remission and discontinuation of insulin therapy, both Akt-2 expression and insulin-stimulated Akt-2 Ser474 phosphorylation doubled. Hyperglycemic crisis did not affect insulin-stimulated threonine phosphorylation of either Akt-1 or Akt-2. The decreased Akt-2 expression at presentation was accompanied by reduced GLUT4 protein expression and increased expression of enzymes counterregulatory to insulin action. Thus a physiological concentration of insulin stimulated Akt-1 and Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression and stimulation appeared to be impaired in muscle of obese patients with atypical diabetes presenting with severe hyperglycemia.


2021 ◽  
Author(s):  
Sue M Ronaldson ◽  
George D Stephenson ◽  
Stewart I Head

The single skinned muscle fibre technique was used to investigate Ca2+- and Sr2+- activation properties of skeletal muscle fibres from elderly women (66-90 years). Muscle biopsies were obtained from the vastus lateralis muscle. Three populations of muscle fibres were identified according to their specific Sr2+- activation properties: slow-twitch (type I) fast-twitch (type II) and hybrid (type I/II) fibres. All three fibre types were sampled from the biopsies of 66 to 72 years old women, but the muscle biopsies of women older than 80 years yielded only slow-twitch (type I) fibres. The proportion of hybrid fibres in the vastus lateralis muscle of women of circa 70 years of age (24%) was several-fold greater than in the same muscle of adults (<10%), suggesting that muscle remodelling occurs around this age. There were no differences between the Ca2+- and Sr2+- activation properties of slow-twitch fibres from the two groups of elderly women, but there were differences compared with muscle fibres from adults with respect to sensitivity to Ca2+, steepness of the activation curves, and characteristics of the fibre-type dependent phenomenon of spontaneous force oscillations (SOMO) occurring at sub-maximal levels of activation. The maximal Ca2+ activated specific force from all the fibres collected from the seven old women use in the present study was significantly lower by 20% than in the same muscle of adults. Taken together these results show there are qualitative and quantitative changes in the activation properties of the contractile apparatus of muscle fibres from the vastus lateralis muscle of women with advancing age, and that these changes need to be considered when explaining observed changes in womens mobility with aging.


2002 ◽  
Vol 58 (1) ◽  
pp. 28-33 ◽  
Author(s):  
M. N. Deane ◽  
M. A. Gregory ◽  
M. Mars

Deep transverse friction (DTF) is used in clinical practice and by its nature it may cause muscle injury. This study investigates the morphologic and morphometric changes in untraumatised rabbit skeletal muscle treated with DTF.Method: 16 New Zealand white rabbits were studied. The right vastus lateralis muscle was used as a control and the left vastus lateralis was treated with DTF. Muscle biopsies were taken 10 min, 24 h and 48 h after 1 treatment, 48 h after 2 treatments and 48 h and 6 days after 3 treatments.  Treatments were 48 h apart. Biopsies were prepared for light microscopy and tissue morphometry.Results: After 1 DTF treatment, intracellular and extracellular oedema was noted. Contraction bands seen throughout the fibres suggested severe mechanical trauma to the muscle. 48 hours after 1, 2, and 3 treatments, the muscle appeared to be recovering with reduced oedema, and the contraction banding was limited to small focal areas throughout each fibre. Six days after the last treatment, the myofibers, although normal in diameter, showed small focal areas of super contraction and large internalised inclusion bodies composed of a pool of myofilaments or whorls of membranous material. Morphometry showed oedema to be maximal immediately after treatment.Conclusion: DTF causes a severe but reversible injury to untraumatized myofibers. Its possible mode of action in treatment of injured muscle requires further investigation.


2015 ◽  
Vol 119 (10) ◽  
pp. 1118-1126 ◽  
Author(s):  
Oliver Baum ◽  
Jennifer Gübeli ◽  
Sebastian Frese ◽  
Eleonora Torchetti ◽  
Corinna Malik ◽  
...  

The ultrastructure of capillaries in skeletal muscle was morphometrically assessed in vastus lateralis muscle (VL) biopsies taken before and after exercise from 22 participants of two training studies. In study 1 (8 wk of ergometer training), light microscopy revealed capillary-fiber (C/F) ratio (+27%) and capillary density (+16%) to be higher ( P ≤ 0.05) in postexercise biopsies than in preexercise biopsies from all 10 participants. In study 2 (6 mo of moderate running), C/F ratio and capillary density were increased (+23% and +20%; respectively, P ≤ 0.05) in VL biopsies from 6 angiogenesis responders (AR) after training, whereas 6 nonangiogenesis responders (NR) showed nonsignificant changes in these structural indicators (−4%/−4%, respectively). Forty capillary profiles per participant were evaluated by point and intersection counting on cross sections after transmission electron microscopy. In study 1, volume density (Vv) and mean arithmetic thickness (T) of endothelial cells (ECs; +19%/+17%, respectively) and pericytes (PCs; +20%/+21%, respectively) were higher ( P ≤ 0.05), whereas Vv and T of the pericapillary basement membrane (BM) were −23%/−22% lower ( P ≤ 0.05), respectively, in posttraining biopsies. In study 2, exercise-related differences between AR and NR-groups were found for Vv and T of PCs (AR, +26%/+22%, respectively, both P ≤ 0.05; NR, +1%/−3%, respectively, both P > 0.05) and BM (AR, −14%/−13%, respectively, both P ≤ 0.05; NR, −9%/−11%, respectively, P = 0.07/0.10). Vv and T of ECs were higher (AR, +16%/+18%, respectively; NR, +6% /+6%, respectively; all P ≤ 0.05) in both groups. The PC coverage was higher (+13%, P ≤ 0.05) in VL biopsies of individuals in the AR group but nonsignificantly altered (+3%, P > 0.05) in those of the NR group after training. Our study suggests that intensified PC mobilization and BM thinning are related to exercise-induced angiogenesis in human skeletal muscle, whereas training per se induces EC-thickening.


2005 ◽  
Vol 288 (6) ◽  
pp. E1265-E1269 ◽  
Author(s):  
Anne Lene Dalkjær Riis ◽  
Jens Otto Lunde Jørgensen ◽  
Niels Møller ◽  
Jørgen Weeke ◽  
Torben Clausen

Skeletal muscle constitutes the major target organ for the thermogenic action of thyroid hormone. We examined the possible relation between energy expenditure (EE), thyroid status, and the contents of Ca2+-ATPase and Na+-K+-ATPasein human skeletal muscle. Eleven hyperthyroid patients with Graves' disease were studied before and after medical treatment with methimazole and compared with eight healthy subjects. Muscle biopsies were taken from the vastus lateralis muscle, and EE was determined by indirect calorimetry. Before treatment, the patients had two- to fivefold elevated total plasma T3 and 41% elevated EE compared with when euthyroidism had been achieved. In hyperthyroidism, the content of Ca2+-ATPase was increased: (mean ± SD) 6,555 ± 604 vs. 5,212 ± 1,580 pmol/g in euthyroidism ( P = 0.04) and 4,523 ± 1,311 pmol/g in healthy controls ( P = 0.0005). The content of Na+-K+-ATPase showed 89% increase in hyperthyroidism: 558 ± 101 vs. 296 ± 34 pmol/g ( P = 0.0001) in euthyroidism and 278 ± 52 pmol/g in healthy controls ( P < 0.0001). In euthyroidism, the contents of both cation pumps did not differ from those of healthy controls. The Ca2+-ATPase content was significantly correlated to plasma T3 and resting EE. This provides the first evidence that, in human skeletal muscle, the capacity for Ca2+ recycling and active Na+-K+ transport are correlated to EE and thyroid status.


Author(s):  
Jonas Roland Knudsen ◽  
Kaspar W Persson ◽  
Jaroslawna Meister ◽  
Christian Strini Carl ◽  
Steffen H Raun ◽  
...  

In mice, exercise is suggested to activate the mechanistic target of rapamycin complex 2 (mTORC2) in skeletal muscle, and mTORC2 is required for normal muscle glucose uptake during exercise. Whether this translates to human skeletal muscle and what signaling pathways facilitate the exercise-induced mTORC2 activation is unknown but important to determine given the important role of mTORC2 in metabolism. We herein tested the hypothesis that exercise increases mTORC2 activity in human skeletal muscle and investigated if β2-adrenergic receptor (AR) activation mediates exercise-induced mTORC2 activation. We examined several mTORC2 activity readouts (p-NDRG1 Thr346, p-Akt Ser473, p-mTOR S2481, and p-Akt Thr450) in human skeletal muscle biopsies after uphill walking or cycling exercise. In mouse muscles, we assessed mTORC2 activity readouts following acute activation of muscle β2-adrenergic or Gs signaling and during in vivo and ex vivo muscle contractions. Exercise increased phosphorylation of NDRG1 Thr346 in human soleus, gastrocnemius, and vastus lateralis muscle, without changing p-Akt Ser473, p-Akt Thr450, and p-mTOR Ser2481. In mouse muscle, stimulation of β2-adrenergic or Gs signaling and ex vivo contractions failed to increase p-NDRG1 Thr346, while in vivo contractions were sufficient to induce p-NDRG1 Thr346. In conclusion, the mTORC2 activity readout p-NDRG1 Thr346 is a novel exercise-responsive signaling protein in human skeletal muscle. Notably, contraction-induced p-NDRG1 Thr346 appears to require a systemic factor. Unlike exercise, and in contrast to published data obtained in cultured muscles cells, stimulation of β2-adrenergic signaling is not sufficient to trigger NDRG1 phosphorylation in mature mouse skeletal muscle.


2011 ◽  
Vol 301 (4) ◽  
pp. E649-E658 ◽  
Author(s):  
Stine Ringholm ◽  
Rasmus S. Biensø ◽  
Kristian Kiilerich ◽  
Amelia Guadalupe-Grau ◽  
Niels Jacob Aachmann-Andersen ◽  
...  

The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest. Twelve young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from six of the subjects prior to, immediately after, and 3 h after 45 min of one-legged knee extensor exercise performed before and after bed rest. Maximal oxygen uptake decreased by 4%, and exercise endurance decreased nonsignificantly, by 11%, by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ∼45%, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity ∼8%, and miR-1 and miR-133a content ∼10%. However, cytochrome c and vascular endothelial growth factor (VEGF) protein content as well as capillarization did not change significantly with bed rest. Acute exercise increased AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor-γ coactivator-1α, and VEGF mRNA content in skeletal muscle before bed rest, but the responses were abolished after bed rest. The present findings indicate that only 7 days of physical inactivity reduces skeletal muscle metabolic capacity as well as abolishes exercise-induced adaptive gene responses, likely reflecting an interference with the ability of skeletal muscle to adapt to exercise.


1998 ◽  
Vol 274 (2) ◽  
pp. E304-E308 ◽  
Author(s):  
Janice A. Koval ◽  
Ralph A. DeFronzo ◽  
Robert M. O’Doherty ◽  
Richard Printz ◽  
Hossein Ardehali ◽  
...  

A single bout of exercise increases the rate of insulin-stimulated glucose uptake and metabolism in skeletal muscle. Exercise also increases insulin-stimulated glucose 6-phosphate in skeletal muscle, suggesting that exercise increases hexokinase activity. Within 3 h, exercise increases hexokinase II (HK II) mRNA and activity in skeletal muscle from rats. It is not known, however, if a single bout of moderate-intensity exercise increases HK II expression in humans. The present study was undertaken to answer this question. Six subjects had percutaneous biopsies of the vastus lateralis muscle before and 3 h after a single 3-h session of moderate-intensity aerobic (60% of maximal oxygen consumption) exercise. Glycogen synthase, HK I, and HK II activities as well as HK I and HK II mRNA content were determined from the muscle biopsy specimens. The fractional velocity of glycogen synthase was increased by 446 ± 84% after exercise ( P < 0.005). Hexokinase II activity in the soluble fraction of the homogenates increased from 1.2 ± 0.4 to 4.5 ± 1.6 pmol ⋅ min−1 ⋅ μg−1( P < 0.05) but was unchanged in the particulate fraction (4.3 ± 1.3 vs. 5.3 ± 1.5). HK I activity in neither the soluble nor particulate fraction changed after exercise. Relative to a 28S rRNA control signal, HK II mRNA increased from 0.091 ± 0.02 to 0.195 ± 0.037 ( P < 0.05), whereas HK I mRNA was unchanged (0.414 ± 0.061 vs. 0.498 ± 0.134, P < 0.20). The increase in HK II activity after moderate exercise in healthy subjects could be one factor responsible for the enhanced rate of insulin-stimulated glucose uptake seen after exercise.


2000 ◽  
Vol 279 (1) ◽  
pp. R152-R160 ◽  
Author(s):  
Niels Ørtenblad ◽  
Per K. Lunde ◽  
Klaus Levin ◽  
Jesper L. Andersen ◽  
Preben K. Pedersen

To evaluate the effect of intermittent sprint training on sarcoplasmic reticulum (SR) function, nine young men performed a 5 wk high-intensity intermittent bicycle training, and six served as controls. SR function was evaluated from resting vastus lateralis muscle biopsies, before and after the training period. Intermittent sprint performance (ten 8-s all-out periods alternating with 32-s recovery) was enhanced 12% ( P < 0.01) after training. The 5-wk sprint training induced a significantly higher ( P < 0.05) peak rate of AgNO3-stimulated Ca2+ release from 709 (range 560–877; before) to 774 (596–977) arbitrary units Ca2+ ⋅ g protein− 1 ⋅ min− 1(after). The relative SR density of functional ryanodine receptors (RyR) remained unchanged after training; there was, however, a 48% ( P < 0.05) increase in total number of RyR. No significant differences in Ca2+ uptake rate and Ca2+-ATPase capacity were observed following the training, despite that the relative density of Ca2+-ATPase isoforms SERCA1 and SERCA2 had increased 41% and 55%, respectively ( P < 0.05). These data suggest that high-intensity training induces an enhanced peak SR Ca2+ release, due to an enhanced total volume of SR, whereas SR Ca2+ sequestration function is not altered.


1989 ◽  
Vol 66 (1) ◽  
pp. 72-78 ◽  
Author(s):  
L. Martineau ◽  
I. Jacobs

The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance.


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