Bioenergetic approach to transfer function of human skeletal muscle

1994 ◽  
Vol 77 (4) ◽  
pp. 1784-1789 ◽  
Author(s):  
T. Binzoni ◽  
P. Cerretelli
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Transfer Function ◽  
Human Skeletal Muscle ◽  
Constant Load ◽  
Aerobic Activity ◽  
Relationship Of ◽  
Kinetics Of ◽  
Constant Load Exercise

A mathematical model analogous to Chance's “transfer function” was derived on the basis of the energy consumption principle, which is suitable to describe the energetics of human skeletal muscle during aerobic activity. The implications and the characteristics of this model are that 1) the half time of phosphocreatine (PCr) hydrolysis at the onset of a mechanical constant-load exercise is independent of the imposed charge, 2) the changes of O2 consumption in the muscle at steady state when changing workload are linearly related to PCr concentration, 3) the kinetics of the intracellular oxygen consumption during a rest-to-work transient are influenced by anaerobic glycolysis, 4) it may explain the PCr-time relationship of different muscles types (e.g., skeletal, heart, trained vs. untrained), 5) it allows one to interpret correctly the significance of the oxygen consumption kinetics in the rest-to-work transient at the lung level, and 6) it is conceived for in vivo applications.

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.

scholarly journals SIMILARITY OF THE KINETICS OF INVERTASE ACTION IN VIVO AND IN VITRO. II

1932 ◽  
Vol 16 (2) ◽  
pp. 233-242 ◽  
Author(s):  
B. G. Wilkes ◽  
Elizabeth T. Palmer
Keyword(s):  
Physiological Activity ◽  
Outer Region ◽  
Living Cells ◽  
Yeast Cells ◽  
Live Cells ◽  
Intracellular Enzyme ◽  
Relationship Of ◽  
Kinetics Of

1. The pH-activity relationship of invertase has been studied in vivo and in vitro under identical external environmental conditions. 2. The effect of changing (H+) upon the sucroclastic activity of living cells of S. cerevisiae and of invertase solutions obtained therefrom has been found, within experimental error, to be identical. 3. The region of living yeast cells in which invertase exerts its physiological activity changes its pH freely and to the same extent as that of the suspending medium. It is suggested that this may indicate that this intracellular enzyme may perform its work somewhere in the outer region of the cell. 4. In using live cells containing maltase, no evidence of increased sucroclastic activity around pH 6.9, due to the action of Weidenhagen's α-glucosidase (maltase), was found.

Abstract 121: Development of Enzyme Replacement Therapy in Mammalian Models of Barth Syndrome

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Ana Dinca ◽  
Wei-Ming Chien ◽  
Michael Chin
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Cell Line ◽  
Single Gene ◽  
Barth Syndrome ◽  
Protein Therapy ◽  
Knock Out ◽  
Enzyme Replacement ◽  
C Terminus

Barth Syndrome (BTHS) is caused by a single gene mutation in the mitochondrial transacylase, tafazzin (TAZ), which results in impaired lipid metabolism leading to dysfunction in highly energetic tissues such as the heart and skeletal muscle. TAZ remodels the signature mitochondrial phospholipid, cardiolipin (CL), which is responsible for providing support to the electron transport chain. BTHS patients suffer from growth deficiencies, cardiomyopathy, hypotonia and neutropenia. Currently, treatment for patients with BTHS is supportive, seeking to ameliorate rather than prevent heart problems, skeletal muscle problems and recurring infections. Protein therapy, on the other hand, might treat and even prevent cardiac, skeletal muscle as well as infection-related morbidities. We designed a recombinant TAZ protein containing a cell penetrating peptide in its C-terminus, which enables the recombinant TAZ to penetrate cells and then treated TAZ-deficient cells with it. We tested the permeability of the recombinant protein by direct delivery to H9C2 cardiomyoblasts and found that the protein is successfully taken up by the cells. We have generated a CRISPR-mediated TAZ knock out cardiomyoblast cell line and we found that TAZ knock out cells show a decrease in oxygen consumption as compared to the wild type cells; this is consistent with data from BTHS patient-derived cells. We are using this cell line to assess the enzymatic activity of the delivered protein by conducting mitochondrial respiration measurements. We have also acquired a mouse model of BTHS and are testing the recombinant TAZ in vivo. Preliminary data shows an augmentation in oxygen consumption following treatment with TAZ. These results indicate that the protein is able to reach the mitochondria, where it is enzymatically active and able to enhance respiration. As the protein is able to rescue respiration in cells in which tafazzin was absent, this suggests that our approach should not only be able to prevent onset of symptoms, but also rescue the phenotype in already affected tissues.

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.

scholarly journals Kinetics of GLUT4 Trafficking in Rat and Human Skeletal Muscle

Diabetes ◽  
2009 ◽  
Vol 58 (4) ◽  
pp. 847-854 ◽  
Author(s):  
H. K.R. Karlsson ◽  
A. V. Chibalin ◽  
H. A. Koistinen ◽  
J. Yang ◽  
F. Koumanov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Kinetics Of

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.

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