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Biomedical subjects

P Schjerling

Publications and source records attributed to P Schjerling.

At least 19 recordsLinked to original sources
PubMed2006

Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types.

In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) (P < 0.05), but the effect of eccentric training was greater than concentric and isometric training (P < 0.05). In tendon, myostatin mRNA was detected, but no changes were seen after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon (up to 4-fold) in response to training (P < 0.01). In tendon no difference was seen between training types, but in muscle the effect of eccentric training was greater than concentric training for both IGF-IEa and MGF (P < 0.05), and for IGF-IEa isometric training had greater effect than concentric (P < 0.05). The results indicate a possible role for IGF-IEa and MGF in adaptation of tendon to training, and the combined changes in myostatin and IGF-IEa/MGF expression could explain the important effect of eccentric actions for muscle hypertrophy.

Animals↗
PubMed2006

The possible role of myostatin in skeletal muscle atrophy and cachexia.

The presence of sufficient skeletal muscle is of paramount importance for body function. Cachexia can be defined as a wasting syndrome describing the progressive loss of both adipose and skeletal muscle tissue in concert with severe injury, chronic or end-stage malignant and infectious diseases. Generally, cachexia predisposes to poor prognosis, co-morbidities and death. One signaling pathway possibly involved in muscle atrophy and cachexia is the myostatin cascade. This transforming growth factor-beta superfamily member myostatin is a strong candidate for regulating muscle mass, and is shown to inhibit muscle growth in different in vivo mammalian models. Overall, the modulation of the myostatin pathway seems interesting from the perspective of both pathology and sports medicine. Hence, myostatin signaling components and post-translational modulators are possible targets of pharmacological and other treatments against muscle loss, thus potentially contributing to the understanding and mitigation of muscle atrophies associated with inactivity, senescence and disease.

Animals↗
PubMed2005

Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in human skeletal muscle: influence of gender and exercise.

AIM: To investigate gender-related differences in the responses of oxidative enzymes and eukaryotic elongation factor-2 (eEF2) to exercise. METHODS: The influence of exercise (90 min, 60%VO(2peak)) on citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (HAD) activity and mRNA content, together with eEF2 expression and phosphorylation at rest, were assessed in skeletal muscle of untrained (UT) and endurance trained (ET) females and males. RESULTS: Citrate synthase and HAD mRNA were higher in females than in males (27% and 48%, respectively, P < 0.05) whereas CS and HAD activity did not differ between females and males (NS). In females only, CS activity was enhanced (P < 0.05) by 90 min exercise. Resting CS mRNA content did not differ between UT and ET but, nevertheless, CS activity was 56% higher in ET than in UT volunteers (P < 0.001). HAD mRNA and activity were not influenced by training status (NS). In UT, CS mRNA was enhanced 37% (P < 0.05) by exercise whereas exercise did not change CS mRNA in ET (NS). eEF2 expression was 31% higher (P < 0.05) and eEF2 Thr56 phosphorylation (which leads to translation inhibition) was 24% lower (P < 0.05) in females than in males. eEF2 expression and phosphorylation were unaffected by training status (NS). CONCLUSION: Basal transcriptional, translational, and/or post-translational control of CS and HAD seems to be gender-dependent. Also, gender differences in translation and/or post-translational protein modification of CS occur during exercise. Accordingly, the potential for peptide-chain elongation, based on eEF2 expression and phosphorylation, appears to be higher in females than in males.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2004

Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells.

The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the proliferative effect of extracellular medium was determined in non-stimulated and electro-stimulated rat and human skeletal muscle cells. In rat skeletal muscle cells these aspects were also determined after treatment with inhibitors and/or donors of nitric oxide (NO), prostanoids and adenosine. Electro-stimulation caused an elevation in the VEGF and bFGF mRNA levels of rat muscle cells by 33% and 43% (P < 0.05), respectively, and in human muscle cells VEGF mRNA was elevated by 24%. Medium from electro-stimulated human, but not rat muscle cells induced a 126% higher (P < 0.05) endothelial cell proliferation than medium from non-stimulated cells. Cyclooxygenase inhibition of rat muscle cells induced a 172% increase (P < 0.05) in VEGF mRNA and a 104% increase in the basal VEGF release. Treatment with the NO donor SNAP (0.5 microM) decreased (P < 0.05) VEGF and bFGF mRNA by 42 and 38%, respectively. Medium from SNAP treated muscle cells induced a 45% lower (P < 0.05) proliferation of endothelial cells than control medium. Adenosine enhanced the basal VEGF release from muscle cells by 75% compared to control. The present data demonstrate that contractile activity, NO, adenosine and products of cyclooxygenase regulate the expression of VEGF and bFGF mRNA in skeletal muscle cells and that contractile activity and NO regulate endothelial cell proliferative compounds in muscle extracellular fluid.

Adenosine↗
PubMed2003

The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.

The expression of two isoforms of insulin-like growth factor-I (IGF-I): mechano growth factor (MGF) and IGF-IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF-IEb was also investigated in response to resistance training only. The subjects (age 74 +/- 1 years, mean +/- S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF-IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF-IEa (68%) and IGF-IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF-IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.

Aged↗
PubMed2003

Resistance training and insulin action in humans: effects of de-training.

Aerobic endurance training increases insulin action in skeletal muscle, but the effect of resistance training has not been well described. Controversy exists about whether the effect of resistance training is merely due to an increase in muscle mass. We studied the effect of cessation of resistance training in young, healthy subjects by taking muscle biopsies and measuring insulin-mediated whole body and leg glucose uptake rates after 90 days of heavy resistance training (T) and again after 90 days of de-training (dT). Data on leg glucose uptake were expressed relative to accurate measures of leg muscle mass by MRI scanning. Muscle strength (239 +/- 43 vs. 208 +/- 33 N m), quadriceps area (8463 +/- 453 vs. 7763 +/- 329 mm2) and glycogen content (458 +/- 22 vs. 400 +/- 26 mmol (kg dry weight muscle)(-1)) decreased, while myosin heavy chain isoform IIX increased 4-fold in dT vs. T, respectively (all P < 0.05). GLUT4 mRNA levels and enzyme activities and mRNA levels of glycolytic, lipolytic and glyconeogenic enzymes did not change with de-training. Likewise, capillary density did not change. Whole body glucose uptake decreased 11 % and leg glucose uptake decreased from 75 +/- 11 (T) to 50 +/- 6 (dT) nmol min(-1) (mm muscle)(-2) (P < 0.05) at maximal insulin, the latter decrease being due to decreased arterio-femoral venous glucose extraction. The decrease was mainly due to reduced non-oxidative glucose disposal. We have thus shown that 90 days after the termination of heavy resistance training, insulin-mediated glucose uptake rates per unit of skeletal muscle have decreased significantly.

Adult↗
PubMed2002

Proliferation and telomere length in acutely mobilized blood mononuclear cells in HIV infected patients.

The aim of the study was to investigate the mobilization of T cells in response to a stressful challenge (adrenalin stimulation), and to access T cells resided in the peripheral lymphoid organs in HIV infected patients. Seventeen patients and eight HIV seronegative controls received an adrenalin infusion for 1 h. Blood was sampled before, during and 1 h after adrenalin infusion. Proliferation and mean telomere restriction fragment length (telomeres) of blood mononuclear cells (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In patients, the proliferation to pokeweed mitogens (PWM) was lower and decreased more during adrenalin infusion. After adrenalin infusion the proliferation to PWM was restored only in the controls. In all subjects telomeres in CD4+ cells declined during adrenalin infusion. Additionally, the patients had shortened telomeres in their CD8+ cells, and particularly HAART treated patients had shortened telomeres in all cell-subtypes. The finding that patients mobilized cells with an impaired proliferation to PWM during and after adrenalin infusion has possible clinical relevance for HIV infected patients during pathological stressful conditions, such as sepsis, surgery and burns. However, this study did not find a correlation between impaired proliferation and telomeres. It is concluded that physiological stress further aggravates the HIV-induced immune deficiency.

Adult↗
PubMed2002

LPS-induced cytokine production in the monocytic cell line THP-1 determined by multiple quantitative competitive PCR (QC-PCR).

BACKGROUND: Quantifying cytokines on the protein level can be problematic because of low concentrations or degradation during sample handling. Aiming towards finding a simple method by which to quantify cytokines on the mRNA level, we combined existing and established molecular biology techniques. Based on the principle of quantitative competitive RT-PCR with a DNA-competitor, IL-1beta, IL-6, IL-12alpha and the housekeeping enzyme GAPDH are measured at levels down to 200 copies of mRNA. METHODS: As a source of mRNA, the total RNA from 4 samples of 5 x 10(6) THP-1 cells stimulated with LPS (1 microg/ml for 24 h) was isolated. For competitors, we constructed sequences similar to the target sequences, but with deletion or insertion of 10-15% of the target length. For validating this method, we performed first strand synthesis on different days using different amounts of RNA (1-4 microg) isolated from the same pool of cells. Quantitative competitive PCR was accomplished using different amounts of cDNA (0.125-4 microL). Using IL-1beta as an example, the assay was validated for a dynamic range of 5-300 x 10(3) copies. RESULTS: A linear correlation was found between output and amount of RNA for cDNA synthesis, signifying that the final result of the analysis was linearly related to the amount of RNA or cDNA when operating within the range 1-4 microg (RNA isolation). CONCLUSION: The quantitative, competitive RT-PCR produces highly reproducible results within a 60-fold dynamic range.

Cell Line↗
PubMed2001

Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content.

1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both legs. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery. 3. Pre-exercise glycogen content was lower in the glycogen-depleted leg compared with the control leg. Intramuscular IL-6 mRNA levels increased with exercise in both legs, but this increase was augmented in the leg having the lowest glycogen content at end-ex. The arterial plasma concentration of IL-6 increased from 0.6 +/- 0.1 ng x l(-1) pre-ex to 21.7 +/- 5.6 ng x l(-1) end-ex. The depleted leg had already released IL-6 after 1 h (4.38 +/- 2.80 ng x min(-1) (P < 0.05)), whereas no significant release was observed in the control leg (0.36 +/- 0.14 ng x min(-1)). A significant net IL-6 release was not observed until 2 h in the control leg. 4. This study demonstrates that glycogen availability is associated with alterations in the rate of IL-6 production and release in contracting skeletal muscle.

Adult↗
PubMed2001

Muscle-derived interleukin-6: possible biological effects.

Interleukin-6 (IL-6) is produced locally in working skeletal muscle and can account for the increase in plasma IL-6 during exercise. The production of IL-6 during exercise is related to the intensity and duration of the exercise, and low muscle glycogen content stimulates the production. Muscle-derived IL-6 is released into the circulation during exercise in high amounts and is likely to work in a hormone-like fashion, exerting an effect on the liver and adipose tissue, thereby contributing to the maintenance of glucose homeostasis during exercise and mediating exercise-induced lipolysis. Muscle-derived IL-6 may also work to inhibit the effects of pro-inflammatory cytokines such as tumour necrosis factor alpha. The latter cytokine is produced by adipose tissue and inflammatory cells and appears to play a pathogenetic role in insulin resistance and atherogenesis.

Humans↗
PubMed2001

Chemokines are elevated in plasma after strenuous exercise in humans.

During the last few years much attention has been paid to the chemokines. Chemokine receptors are necessary to render a target permissive for infection by the human immunodeficiency virus (HIV) and high concentrations of chemokines have been shown to protect against the progression of HIV disease towards death. In the present study, we investigated the capability of strenuous exercise to induce elevated plasma concentrations of the chemokines interleukin (IL)-8, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. Eight male athletes completed the Copenhagen Marathon 1997. Blood was sampled before, immediately after the run and every 30 min during a 4 h recovery period. Plasma chemokine concentrations were measured using enzyme-linked immunosorbent assays. The IL-8, MIP-1 alpha and MIP-1 beta concentrations all peaked 0.5 h after the run when they were 6.7-fold, 3.5-fold and 4.1-fold increased, respectively. The elevated concentrations of chemokines in plasma after exercise could have implications for HIV-infected individuals; a possibility that needs further investigation.

Adult↗
PubMed2001

Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected patients.

In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 x 106 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03) and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naïve and memory phenotype within both CD4+ and CD8+ cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

Adjuvants, Immunologic↗
PubMed2001

T-cell mean telomere lengths changes in treatment naïve HIV-infected patients randomized to G-CSF or placebo simultaneously with initiation of HAART.

The effect of highly active antiretroviral therapy (HAART) and granulocyte colony stimulating factor (G-CSF) on mean telomere restriction fragment (TRF) length of peripheral blood mononuclear cells (PBMC) was examined in 11 treatment naïve human immunodeficiency virus (HIV)-infected individuals with a CD4+ T-cell count < 350 cells/mm3. Patients were randomized to HAART combined with G-CSF thrice weekly for 12 weeks (n = 6) or placebo (n = 5). An increase in the mean TRF lengths was observed in PBMC of patients on HAART after 24 weeks of treatment mainly owing to increased mean CD8+ T-cell TRF lengths. However, in the group of patients on HAART combined with G-CSF no changes of PBMC mean TRF length was observed during treatment or during 12 weeks of follow-up. The mean CD4+ T-cell TRF length did not change in any of the two groups. These results confirm that HAART induces mainly the lengthening of the mean CD8+ T-cell TRF length. However, G-CSF given simultaneously with HAART induces an inhibition of the expected lengthening in mean TRF length. These results do therefore not support the use of adjuvant G-CSF treatment simultaneously when initiating HAART and should further be evaluated before use in non-neutropenic HIV-infected patients.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and facioscapulo human muscular dystrophy. A potential target for pharmacological treatment?

Apoptosis was detected in different muscular diseases, including severe dystrophin deficiency, but apoptotic mechanisms are not completely described in adult skeletal muscle. Studying patients affected by Duchenne muscular dystrophy (DMD) and by facio-scapulo-humeral dystrophy (FSHD) we showed an increase of apoptotic myonuclei, bax, and bcl-2-positive myofibers. Positive correlation was detected between apoptotic nuclei and bax expression (p < 0.01). Expression of caspases was analyzed by RNase protection. Caspase transcript was not detected in normal skeletal muscles. DMD muscles expressed caspase 8, 3, 5, 2, 7 and Granzyme B mRNAs. Low levels of caspase 6, 3, and Granzyme B transcripts were detected in FSHD patients. Tissue levels of caspase 3 protein significantly correlated with apoptotic myonuclei (p < 0.05) and with bax expression (p < 0.01). In all DMD cases the activity of caspase 3 was increased, while the FSHD samples were heterogeneous. These data indicate that human skeletal muscle fibers. during the dystrophic process, modulate the expression of caspases and that caspase 3 is involved in myofiber cell death. opening new perspective in the pharmacological treatments of muscular dystrophies, such as the use of caspase inhibitors.

Adolescent↗
PubMed2001

Exercise and interleukin-6.

Strenuous exercise induces increased levels in a number of pro-and anti-inflammatory cytokines, natural occurring cytokine inhibitors, and chemokines. Thus, increased plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases as much as 100-fold after a marathon race. It has recently been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial concentration. Larger amounts of IL-6 are produced in response to exercise than any other cytokine, IL-6 is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose output and to induce lipolysis. These facts indicate that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.

Cytokines↗
PubMed2001

Plasma interleukin-6 during strenuous exercise: role of epinephrine.

Exercise induces increased levels of plasma interleukin-6 (IL-6) as well as changes in the concentration of lymphocytes and neutrophils. The aim of this study was to investigate a possible role for epinephrine. Seven healthy men participated in an exercise experiment. One month later they received an epinephrine infusion. The exercise consisted of treadmill running at 75% of maximal O(2) consumption for 2.5 h. The infusion trial consisted of 2.5 h of epinephrine infusion calculated to reach the same plasma epinephrine levels seen during the exercise experiment. The plasma concentration of IL-6 increased 29-fold during exercise, with peak levels at the end of exercise. The increase in plasma IL-6 during epinephrine infusion was only sixfold, with the peak value at 1 h after infusion. The lymphocyte concentration increased to the same levels during exercise and epinephrine infusion. The lymphocyte count decreased more in the postexercise period than after epinephrine infusion. The neutrophil concentration was elevated threefold in response to exercise, whereas no change was found in response to epinephrine infusion. In conclusion, the exercise-induced increase in plasma IL-6 could not be mimicked by epinephrine infusion. However, epinephrine induced a small increase in IL-6 and may, therefore, partly influence the plasma levels of IL-6 during exercise. In addition, the results support the idea that epinephrine plays a role in exercise-induced changes in lymphocyte number, whereas epinephrine does not mediate exercise-induced neutrocytosis.

Adult↗
PubMed2001

Exercise and cytokines with particular focus on muscle-derived IL-6.

Exercise induces increased circulating levels of a number of cytokines. Thus, increased plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL-1) beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases up to 100 fold after a marathon race. Recently, it has been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial IL-6 concentration. IL-6 more than any other cytokine is produced in large amounts in response to exercise. It is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose-output and to induce lipolysis. This indicates that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.

Animals↗