scholarly journals The breaking and making of healthy adult human skeletal muscle in vivo

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Abigail L. Mackey ◽  
Michael Kjaer
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Healthy Adult ◽  
Adult Human

Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle

2015 ◽  
Vol 118 (8) ◽  
pp. 971-979 ◽  
Author(s):  
Andreas Buch Møller ◽  
Mikkel Holm Vendelbo ◽  
Britt Christensen ◽  
Berthil Forrest Clasen ◽  
Ann Mosegaard Bak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Physical Exercise ◽  
Light Chain ◽  
Human Skeletal Muscle ◽  
Transgenic Animal ◽  
Dependent Manner ◽  
Healthy Humans ◽  
Transgenic Animal Models ◽  
Exercise Induced

Data from transgenic animal models suggest that exercise-induced autophagy is critical for adaptation to physical training, and that Unc-51 like kinase-1 (ULK1) serves as an important regulator of autophagy. Phosphorylation of ULK1 at Ser555 stimulates autophagy, whereas phosphorylation at Ser757 is inhibitory. To determine whether exercise regulates ULK1 phosphorylation in humans in vivo in a nutrient-dependent manner, we examined skeletal muscle biopsies from healthy humans after 1-h cycling exercise at 50% maximal O2 uptake on two occasions: 1) during a 36-h fast, and 2) during continuous glucose infusion at 0.2 kg/h. Physical exercise increased ULK1 phosphorylation at Ser555 and decreased lipidation of light chain 3B. ULK1 phosphorylation at Ser555 correlated positively with AMP-activated protein kinase-α Thr172 phosphorylation and negatively with light chain 3B lipidation. ULK1 phosphorylation at Ser757 was not affected by exercise. Fasting increased ULK1 and p62 protein expression, but did not affect exercise-induced ULK1 phosphorylation. These data demonstrate that autophagy signaling is activated in human skeletal muscle after 60 min of exercise, independently of nutritional status, and suggest that initiation of autophagy constitutes an important physiological response to exercise in humans.

Differential patterns of transcript accumulation during human myogenesis

1987 ◽  
Vol 7 (11) ◽  
pp. 4100-4114
Author(s):  
P Gunning ◽  
E Hardeman ◽  
R Wade ◽  
P Ponte ◽  
W Bains ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Carbonic Anhydrase ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Time Course ◽  
Human Skeletal Muscle ◽  
Transcript Accumulation ◽  
Mrna Accumulation ◽  
Adult Human ◽  
Alpha Actin

We evaluated the extent to which muscle-specific genes display identical patterns of mRNA accumulation during human myogenesis. Cloned satellite cells isolated from adult human skeletal muscle were expanded in culture, and RNA was isolated from low- and high-confluence cells and from fusing cultures over a 15-day time course. The accumulation of over 20 different transcripts was compared in these samples with that in fetal and adult human skeletal muscle. The expression of carbonic anhydrase 3, myoglobin, HSP83, and mRNAs encoding eight unknown proteins were examined in human myogenic cultures. In general, the expression of most of the mRNAs was induced after fusion to form myotubes. However, several exceptions, including carbonic anhydrase and myoglobin, showed no detectable expression in early myotubes. Comparison of all transcripts demonstrated little, if any, identity of mRNA accumulation patterns. Similar variability was also seen for mRNAs which were also expressed in nonmuscle cells. Accumulation of mRNAs encoding alpha-skeletal, alpha-cardiac, beta- and gamma-actin, total myosin heavy chain, and alpha- and beta-tubulin also displayed discordant regulation, which has important implications for sarcomere assembly. Cardiac actin was the only muscle-specific transcript that was detected in low-confluency cells and was the major alpha-actin mRNA at all times in fusing cultures. Skeletal actin was transiently induced in fusing cultures and then reduced by an order of magnitude. Total myosin heavy-chain mRNA accumulation lagged behind that of alpha-actin. Whereas beta- and gamma-actin displayed a sharp decrease after initiation of fusion and thereafter did not change, alpha- and beta-tubulin were transiently induced to a high level during the time course in culture. We conclude that each gene may have its own unique determinants of transcript accumulation and that the phenotype of a muscle may not be determined so much by which genes are active or silent but rather by the extent to which their transcript levels are modulated. Finally, we observed that patterns of transcript accumulation established within the myotube cultures were consistent with the hypothesis that myoblasts isolated from adult tissue recapitulate a myogenic developmental program. However, we also detected a transient appearance of adult skeletal muscle-specific transcripts in high-confluence myoblast cultures. This indicates that the initial differentiation of these myoblasts may reflect a more complex process than simple recapitulation of development.

Primary structure of the adult human skeletal muscle voltage-dependent sodium channel

1992 ◽  
Vol 31 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Alfred L. George ◽  
Jeffrey Komisarof ◽  
Roland G. Kallen ◽  
Robert L. Barchi
Keyword(s):  
Skeletal Muscle ◽  
Sodium Channel ◽  
Primary Structure ◽  
Human Skeletal Muscle ◽  
Adult Human ◽  
Voltage Dependent

scholarly journals A three-dimensional culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction and disease modeling

2018 ◽  
Author(s):  
Mohsen Afshar Bakooshli ◽  
Ethan S Lippmann ◽  
Ben Mulcahy ◽  
Nisha R Iyer ◽  
Christine T Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Human Skeletal Muscle ◽  
Disease Modeling ◽  
De Novo ◽  
Muscle Fibers ◽  
Three Dimensional ◽  
Adult Human

SummaryTwo-dimensional (2D) human skeletal muscle fiber cultures are ill equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections within two weeks. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium transient imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-culture. This demonstrates that the 3D co-culture system supports a developmental shift from the embryonic to adult form of the receptor that does not occur in 2D co-culture. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. This work delivers a simple, reproducible, and adaptable method to model and evaluate adult human NMJ de novo development and disease in culture.

scholarly journals FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

2021 ◽  
Vol 118 (37) ◽  
pp. e2021013118 ◽  
Author(s):  
Sebastian Mathes ◽  
Alexandra Fahrner ◽  
Umesh Ghoshdastider ◽  
Hannes A. Rüdiger ◽  
Michael Leunig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Human Skeletal Muscle ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Adeno Associated Virus ◽  
Adult Skeletal Muscle

Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus–mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2–dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.

scholarly journals Microdialysis of skeletal muscle at rest

1999 ◽  
Vol 58 (4) ◽  
pp. 919-923 ◽  
Author(s):  
Jan Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Human Metabolism ◽  
High Expectations ◽  
Perfusate Flow ◽  
Muscle Research ◽  
Interstitial Glucose

Techniques in human skeletal muscle research are by necessity predominantly 'descriptive'.Microdialysis has raised high expectations that it could meet the demand for a method that allows 'mechanistic' investigations to be performed in human skeletal muscle. In the present review, some views are given on how well the initial expectations on the use of the microdialysis technique in skeletal muscle have been fulfilled, and the areas in which additional work is needed in order to validate microdialysis as an important metabolic technique in this tissue. The microdialysis catheter has been equated to an artificial blood vessel, which is introduced into the tissue. By means of this 'vessel' the concentrations of compounds in the interstitial space can be monitored. The concentration of substances in the collected samples is dependent on the rate of perfusate flow. When perfusate flow is slow enough to allow complete equilibration between interstitial and perfusate fluids, the concentration in the perfusate is maximal and identical to the interstitial concentration. Microdialysis data may be influenced by changes in blood flow, especially in instances where the tissue diffusivity limits the recovery in vivo, i.e. when recovery in vitro is 100 %, whereas the recovery in vivo is less than 100 %. Microdialysis data indicate that a significant arterial-interstitial glucose concentration gradient exists in skeletal muscle but not in adipose tissue at rest. While the concentrations of glucose and lactate in the dialysate from skeletal muscle are close to the expected values, the glycerol values obtained for muscle are still puzzling. Ethanol added to the perfusate will be cleared by the tissue at a rate that is determined by the nutritive blood flow (the microdialysis ethanol technique). It is concluded that microdialysis of skeletal muscle has become an important technique for mechanistic studies in human metabolism and nutrition.

A Quantitative Evaluation of the Frequency-Response Characteristics of Active Human Skeletal Muscle In Vivo

1979 ◽  
Vol 101 (1) ◽  
pp. 28-37 ◽  
Author(s):  
G. I. Zahalak ◽  
S. J. Heyman
Keyword(s):  
Skeletal Muscle ◽  
Frequency Response ◽  
Human Skeletal Muscle ◽  
Muscle Stiffness ◽  
Forced Oscillations ◽  
Muscle Stretch ◽  
Gain Parameter ◽  
Response Characteristics ◽  
Frequency Response Characteristics

This paper describes an investigation of the frequency-response characteristics of active human skeletal muscle in vivo over the frequency range 1 Hz to 15 Hz. The applied force, forearm position, and surface electromyograms (from biceps, triceps, and brachioradialis) were recorded simultaneously in four normal adult male subjects for small oscillations of the forearm about a mean position of 90 deg flexion. Two modes of oscillatory behavior are discussed: externally forced oscillations under constant muscle force and voluntary oscillations against an elastic resistance. The observed amplitude and phase relations are presented herein and are compared to the response predicted by a simple model for neuromuscular dynamics. It appears that the small amplitude frequency response of normal skeletal muscle in vivo can be represented by a second order model. The main muscle parameters of this model are a muscular stiffness K, two time constants τ1 and τ2 associated with contraction dynamics, and a time delay τ: typical values of these parameters at moderate contraction levels (approximately 20 percent of maximum voluntary effort) are K = 100 N · m/rad, τ1 and τ2 = 50 ms, and τ = 10 ms. Reflex feedback under forced-oscillation conditions was also examined and may be characterized by a gain parameter (ΔE/Δθ), the ratio of the surface EMG amplitude to the angular displacement of the forearm, and the phase by which the EMG leads muscle stretch. The reflex EMG is observed to lead muscle stretch at all frequencies between 1 Hz and 15 Hz. The muscle stiffness K and the reflex gain parameter (ΔE/Δθ) are approximately proportional to the average force of contraction.

Detection of Residual Quadrupolar Interaction in Human Skeletal Muscle and Brain in vivo via Multiple Quantum Filtered Sodium NMR Spectra

1995 ◽  
Vol 33 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Ravinder Reddy ◽  
Lizann Bolinger ◽  
Meir Shinnar ◽  
Elizabeth Noyszewski ◽  
John S. Leigh
Keyword(s):  
Skeletal Muscle ◽  
Nmr Spectra ◽  
Human Skeletal Muscle ◽  
Multiple Quantum ◽  
Quadrupolar Interaction ◽  
Sodium Nmr

Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2

1988 ◽  
Vol 65 (1) ◽  
pp. 487-489 ◽  
Author(s):  
A. Katz ◽  
K. Sahlin ◽  
J. Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Work Load ◽  
Short Term ◽  
Catalytic Function ◽  
Muscle Ph ◽  
Induced Changes ◽  
Femoris Muscle

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.

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