Thorsten Schiffer

Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle

Chaperone-assisted selective autophagy (CASA) is a tension-induced degradation pathway essential for muscle maintenance. Impairment of CASA causes childhood muscle dystrophy and cardiomyopathy. However, the importance of CASA for muscle function in healthy individuals has remained elusive so far. Here we describe the impact of strength training on CASA in a group of healthy and moderately trained men. We show that strenuous resistance exercise causes an acute induction of CASA in affected muscles to degrade mechanically damaged cytoskeleton proteins. Moreover, repeated resistance exercise during 4 wk of training led to an increased expression of CASA components. In human skeletal muscle, CASA apparently acts as a central adaptation mechanism that responds to acute physical exercise and to repeated mechanical stimulation.

Lactate infusion at rest increases BDNF blood concentration in humans

Studies in humans use blood lactate to determine the degree of the exercise intensity, suggesting that exercise with elevated blood lactate concentrations results in increased BDNF plasma concentrations. However, it is not clear if lactate per se or rather other mechanisms are responsible for changes in blood BDNF concentrations. The lactate clamp method at rest is an appropriate method to examine physiological responses of lactate on the human organism without the effects of exercise. Eight male sport students placed in a sitting position received intravenous infusions with a 4 molar sodium-lactate solution in an incremental design starting with an infusion rate of 0.01ml/kgBW/min for the first three minutes, which was increased every three minutes by 0.01ml/kgBW/min up to 0.08ml/kg/min in the 24th minute. All together each subject received 4.2mmol of infusion. Venous blood samples were taken before and immediately after the infusion as well as in the 24th and the 60th min after the infusion period and analysed for BDNF. Blood gases and capillary blood lactate (La) were analysed before the test, every three minutes directly before increasing the infusion rate, at the end of the infusion and in the post infusions period until the 12th min and after 24 and 60min. BDNF and La increased significantly after the infusion and reached baseline values at the end of the experiment (p<0.05, p<0.01, respectively). pH and hydrogen ions increased from the beginning until the end of the infusion period (p<0.01). This data suggest that blood lactate is involved in the regulation of BDNF blood concentrations.

Analysis of the effects of androgens and training on myostatin propeptide and follistatin concentrations in blood and skeletal muscle using highly sensitive Immuno PCR

Myostatin propeptide (MYOPRO) and follistatin (FOLLI) are potent myostatin inhibitors. In this study we analysed effects of training and androgens on MYOPRO and FOLLI concentrations in blood and skeletal muscle using Immuno PCR. Young healthy males performed either a 3-month endurance training or a strength training. Blood and biopsy samples were analysed. Training did not significantly affect MYOPRO and FOLLI concentrations in serum and muscle. To investigate whether total skeletal muscle mass may affect circulating MYOPRO and FOLLI levels, blood samples of tetraplegic patients, untrained volunteers and bodybuilders were analysed. MYOPRO was significantly increased exclusively in the bodybuilder group. In orchiectomised rats MYOPRO increased in blood and muscle after treatment with testosterone. In summary our data demonstrate that moderate training does not affect the concentrations of MYOPRO to FOLLI. In contrast androgen treatment results in a significant increase of MYOPRO in skeletal muscle and serum.

Energy Cost and Pole Forces during Nordic Walking under Different Surface Conditions

INTRODUCTION The purpose of the study was to identify the effect of three different surfaces on energy consumption and the forces acting on the walking poles during ground contact in Nordic walking (NW). METHODS Thirteen female NW instructors (age = 26 +/- 4 yr, weight = 58.5 +/- 4.2 kg, height = 168.1 +/- 4.6 cm) volunteered in the study. The subjects walked a distance of 1200 m at a controlled, constant speed of 2.2 m x s(-1) on each of a concrete surface (C), an artificial athletics track (A), and a naturally grown soccer lawn (G). They used NW poles with inbuilt strain gauge force transducers to measure ground reaction forces acting along the long axes of the poles. Oxygen uptake, capillary blood lactate (La), HR, and RPE were measured before and after the tests. RESULTS Impact forces, maximum forces, force rates during ground contact identified from the registered force time histories, displayed significant differences related to the surface conditions. However, force time integrals did not show surface-related differences. Relative oxygen consumption showed significant differences between NW on C and on G whereas no surface-related differences could be identified between the surface conditions for the parameters La, HR, and RPE. CONCLUSION Our data indicate that the impulse that is generated by the poles on the subjects is identical between the varying surfaces. Because there are differences for the oxygen uptake between C and G, the main regulator for the propulsion must be the musculature of the lower extremities. The work of the upper extremities seems to be a luxury effort for Nordic walkers with a proper technique.

Cardio-respiratory and metabolic responses to different levels of compression during submaximal exercise:

Objective The effects of knee-high socks that applied different levels of compression (0, 10, 20, 30 and 40 mmHg) on various cardio-respiratory and metabolic parameters during submaximal running were analysed. Methods Fifteen well-trained, male endurance athletes (age: 22.2 ± 1.3 years; peak oxygen uptake: 57.2 ± 4.0 mL/minute/kg) performed a ramp test to determine peak oxygen uptake. Thereafter, all athletes carried out five periods of submaximal running (at approximately 70% of peak oxygen uptake) with and without compression socks that applied the different levels of pressure. Cardiac output and index, stroke volume, arterio-venous difference in oxygen saturation, oxygen uptake, arterial oxygen saturation, heart rate and blood lactate were monitored before and during all of these tests. Results Cardiac output (P = 0.29) and index (P = 0.27), stroke volume (P = 0.50), arterio-venous difference in oxygen saturation (P = 0.11), oxygen uptake (P = 1.00), arterial oxygen saturation (P = 1.00), heart rate (P = 1.00) and arterial lactate concentration (P = 1.00) were unaffected by compression (effect sizes = 0.00–0.65). Conclusion This first evaluation of the potential effects of increasing levels of compression on cardio-respiratory and metabolic parameters during submaximal exercise revealed no effects whatsoever.

Intense Resistance Exercise Induces Early and Transient Increases in Ryanodine Receptor 1 Phosphorylation in Human Skeletal Muscle

Background While ryanodine receptor 1 (RyR1) critically contributes to skeletal muscle contraction abilities by mediating Ca2+ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK) senses contraction-induced energetic stress by phosphorylation at Thr172. Phosphorylation of RyR1 at serine2843 (pRyR1Ser2843) results in leaky RyR1 channels and impaired Ca2+homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca2+-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. Purpose Determine the effects and early time-course of resistance exercise on pRyR1Ser2843 and pAMPKThr172 in type I and II myofibers. Methods 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg) performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser2843 and pAMPKThr172 levels were determined by western blot and semi-quantitative immunohistochemistry techniques. Results While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser2843 increased 15 min and peaked 30 min (p<0.01) post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser2843 levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05). pAMPKThr172 also increased 15 to 30 min post exercise (p<0.01) in type I and II myofibers and in whole skeletal muscle. Conclusion Resistance exercise induces acutely increased pRyR1Ser2843 and concomitantly pAMPKThr172 levels for up to 30 min in resistance exercised myofibers. This provides a time-course by which pRyR1Ser2843 can mechanistically impact Ca2+handling properties and consequently induce reduced myofiber contractility beyond immediate fatiguing mechanisms.

Training alters the skeletal muscle antioxidative capacity in non‐insulin‐dependent type 2 diabetic men

The present study analyzes the oxidative stress situation in the skeletal muscle of overweight/obese men suffering from non‐insulin‐dependent type 2 diabetes mellitus [T2DM, n=16, years=61±7, body mass index (BMI)=31±4 kg/m2] and BMI‐matched non‐diabetic male control subjects (CON, n=7, years=53±6, BMI=30±4 kg/m2). Furthermore, it investigates whether physical training can alter the skeletal muscle antioxidative capacity of T2DM patients at rest. Molecule content analyses (immunohistochemical stainings) of 8‐iso‐prostaglandin‐F2α (8‐Iso‐PGF), superoxide dismutase‐2 (SOD2), glutathione peroxidase‐1 (GPX1), peroxiredoxin isoforms (PRDX 1–6) and heat‐shock‐protein‐70 (HSP70) were performed in biopsies taken from the vastus lateralis muscle. Under basal conditions, 8‐Iso‐PGF was significantly decreased in T2DM patients (−35.7%), whereas PRDX2 and PRDX6 were significantly increased relative to CON (+82.6%; +82.3%). Differences were neither observed in SOD2 nor in GPX1 or PRDX1, 3, 4, 5 density. Regular physical activity (moderate endurance or resistance training twice a week for 3 months) did not alter PRDX1, 2, 3, 4, 6 in the skeletal muscle of T2DM patients, but significantly increased SOD2 (+65.9%), GPX1 (+62.4%), PRDX5 (+37.5%), and HSP70 (+48.5%). Overweight/obese men with non‐insulin‐dependent T2DM exhibit up‐regulated cytosolic peroxiredoxin contents relative to BMI‐matched controls. Regular training further up‐regulates cytosolic and mitochondrial antioxidative enzymes in T2DM patients and improves their cellular protection systems. This may contribute to a retardation of the diseases progression.

Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo.

Myogenesis is defined as growth, differentiation and repair of muscles where cell fusion of myoblasts to multinucleated myofibers is one major characteristic. Other cell fusion events in humans are found with bone resorbing osteoclasts and placental syncytiotrophoblasts. No unifying gene regulation for natural cell fusions has been found. We analyzed skeletal muscle biopsies of competitive cyclists for muscle-specific attributes and expression of human endogenous retrovirus (ERV) envelope genes due to their involvement in cell fusion of osteoclasts and syncytiotrophoblasts. Comparing muscle biopsies from post- with the pre-competitive seasons a significant 2.25-fold increase of myonuclei/mm fiber, a 2.38-fold decrease of fiber area/nucleus and a 3.1-fold decrease of satellite cells (SCs) occurred. We propose that during the pre-competitive season SC proliferation occurred following with increased cell fusion during the competitive season. Expression of twenty-two envelope genes of muscle biopsies demonstrated a significant increase of putative muscle-cell fusogenic genes Syncytin-1 and Syncytin-3, but also for the non-fusogenic erv3. Immunohistochemistry analyses showed that Syncytin-1 mainly localized to the sarcolemma of myofibers positive for myosin heavy-chain isotypes. Cellular receptors SLC1A4 and SLC1A5 of Syncytin-1 showed significant decrease of expression in post-competitive muscles compared with the pre-competitive season, but only SLC1A4 protein expression localized throughout the myofiber. Erv3 protein was strongly expressed throughout the myofiber, whereas envK1-7 localized to SC nuclei and myonuclei. Syncytin-1 transcription factors, PPARγ and RXRα, showed no protein expression in the myofiber, whereas the pCREB-Ser133 activator of Syncytin-1 was enriched to SC nuclei and myonuclei. Syncytin-1, Syncytin-3, SLC1A4 and PAX7 gene regulations along with MyoD1 and myogenin were verified during proliferating or actively-fusing human primary myoblast cell cultures, resembling muscle biopsies of cyclists. Myoblast treatment with anti-Synycytin-1 abrogated cell fusion in vitro. Our findings support functional roles for ERV envelope proteins, especially Syncytin-1, contributing to cell fusion of myotubes.

The influence of resistance training on patients with metabolic syndrome--significance of changes in muscle fiber size and muscle fiber distribution.

Geisler, S, Brinkmann, C, Schiffer, T, Kreutz, T, Bloch, W, and Brixius, K. The influence of resistance training on patients with metabolic syndrome-Significance of changes in muscle fiber size and muscle fiber distribution. J Strength Cond Res 25(9): 2598-2604, 2011—People who are afflicted with “metabolic syndrome” exhibit multiple coronary disease risk factors such as insulin resistance, hypertension, hyperlipidemia, or obesity. Twenty-six volunteers (13 women and 13 men) with such disease risk factors (56 ± 5 years) participated in a 14-week resistance training program. Given the fact that resistance training may improve cardiometabolic parameters, the fasting total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, insulin, glucose value, homeostatic model assessment (HOMA) index, and blood pressure and body mass index (BMI) were measured before and after the training intervention. In addition, muscle biopsies from the vastus lateralis muscle of 11 of the men and 5 of the women were analyzed to determine whether changes in the muscle morphology influence the cardiometabolic parameters. Resistance training resulted in a significant increase in fasting HDL for the entire group (from 44.35 ± 9.43 to 48.57 ± 10.96 mg·dl−1, p = 0.016). No other blood parameter changed significantly. No change was observed in the HOMA index, blood pressure, or BMI. The muscle fiber type distribution did not change, but a significant hypertrophy of muscle fibers was evident (an increase of the ellipse minor axis of 67.3 ± 16.6 to 72.1 ± 12.3 μm, p = 0.004). Moderate intensity resistance training, as was performed in our study, induces hypertrophic impulses but does not seem to have a clear positive influence on cardiometabolic risk factors. However, 2 sessions of moderate intensity resistance training per week can enhance the fasting HDL cholesterol in middle-aged subjects.

Kinesio Taping and Jump Performance in Elite Female Track and Field Athletes

CONTEXT The application of kinesio tape (KT) to lower-extremity muscles as an ergogenic aid to improve muscle-strength-related parameters such as jumping is controversial. OBJECTIVE To test the hypothesis that the application of KT enhances the jumping performance of healthy uninjured elite female track and field athletes. DESIGN A double 1-legged jump test was performed before and after the application of blue K-Active tape without traction on the maximally stretched gastrocnemius, hamstrings, rectus femoris, and iliopsoas muscles according to the generally accepted technique. PARTICIPANTS 18 German elite female track and field athletes (age 21 ± 2 y, height 172 ± 4 cm, body mass 62 ± 5 kg, active time in their sport 13 ± 4 y). RESULTS Factorial analysis of variance with repeated measures (ANOVA, Bonferroni) revealed no significant differences in jumping performance between the tests (P > .05, d = 0.26). CONCLUSIONS These findings suggest that the application of KT has no influence on jumping performance in healthy, uninjured female elite athletes. The authors do not recommend the use of KT for the purpose of improving jump performance.