scholarly journals Bed rest increases the amount of mismatched fibers in human skeletal muscle

1999 ◽  
Vol 86 (2) ◽  
pp. 455-460 ◽  
Author(s):  
J. L. Andersen ◽  
T. Gruschy-Knudsen ◽  
C. Sandri ◽  
L. Larsson ◽  
S. Schiaffino
Keyword(s):  
Skeletal Muscle ◽  
Protein Level ◽  
Human Skeletal Muscle ◽  
Muscle Fibers ◽  
Rest Period ◽  
Bed Rest ◽  
Load Bearing ◽  
Transitional State ◽  
Muscle Biopsies

The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expression on both mRNA and protein level in human skeletal muscle fibers were studied. Muscle biopsies from vastus lateralis muscle were obtained from seven healthy young male subjects before and after the bed-rest period. Combined in situ hybridization, immunocytochemistry, and ATPase histochemistry analysis of serial sections of the muscle biopsies demonstrated that fibers showing a mismatch between MHC isoforms at the mRNA and protein level increased significantly after the bed-rest period, suggesting an increase in the amount of muscle fibers in a transitional state. Accordingly, fibers showing a match in expression of MHC-1 and of MHC-2A at the mRNA and protein level decreased, whereas fibers showing a match between MHC-2X mRNA and protein increased after bed rest. Overall, there was an increase in fibers in a transitional state from phenotypic type 1 → 2A and 2A → 2X. Furthermore, a number of fibers with unusual MHC mRNA and isoprotein combinations were observed after bed rest (e.g., type 1 fibers with only mRNA for 2X and type 1 fibers negative for mRNA for MHC-β/slow, 2A, and 2X). In contrast, no changes were revealed after an examination at the protein level alone. These data suggest that the reduced load-bearing activity imposed on the skeletal muscles through bed rest will alter MHC gene expression, resulting in combinations of mRNA and MHC isoforms normally not (or only rarely) observed in muscles subjected to load-bearing activity. On the other hand, the present data also show that 37 days of bed rest are not a sufficient stimulus to induce a similar change at the protein level, as was observed at the gene level.

Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human 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 ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Bed Rest ◽  
Sirtuin 1 ◽  
Vastus Lateralis Muscle ◽  
Before And After ◽  
Exercise Induced ◽  
Muscle Biopsies

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.

scholarly journals THE DISTRIBUTION OF LACTATE DEHYDROGENASE ISOZYMES IN HUMAN SKELETAL MUSCLE FIBERS

1964 ◽  
Vol 12 (8) ◽  
pp. 608-614 ◽  
Author(s):  
M. VAN WIJHE ◽  
M. C. BLANCHAER ◽  
S. ST. GEORGE-STUBBS
Keyword(s):  
Skeletal Muscle ◽  
Lactate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Muscle Fibers ◽  
Isozyme Pattern ◽  
Electrophoretic Separation ◽  
Lactate Dehydrogenase Isozymes ◽  
Dehydrogenase Isozyme ◽  
Lactate Dehydrogenase Isozyme ◽  
Normal Human

A study of the distribution of lactate dehydrogenase isozymes in single fibers from normal human skeletal muscle is presented. The fibers were classified into red, intermediate and white types on histochemical grounds and their lactate dehydrogenase isozyme content assessed by electrophoretic separation in veronal buffered agar. The results generally agreed with previous homogenate studies on animal skeletal muscle, in that the white fibers contained almost exclusively isozymes IV and V, whereas red fibers were rich in isozymes I, II and III, but IV and V also appeared indigenous to these fibers. The intermediate fibers had an isozyme pattern combining the features of red and white fibers. The metabolic implications of these findings are discussed.

RPS6 phosphorylation occurs to a greater extent in the periphery of human skeletal muscle fibers, near focal adhesions, after anabolic stimuli

2021 ◽  
Author(s):  
Nathan Hodson ◽  
Michael Mazzulla ◽  
Maksym N. H. Holowaty ◽  
Dinesh Kumbhare ◽  
Daniel R. Moore
Keyword(s):  
Skeletal Muscle ◽  
Focal Adhesion ◽  
Human Skeletal Muscle ◽  
Muscle Fibers ◽  
Focal Adhesions ◽  
Immunofluorescent Staining ◽  
Whole Body ◽  
Vastus Lateralis Muscle ◽  
Cell Periphery ◽  
Rps6 Phosphorylation

Following anabolic stimuli (mechanical loading and/or amino acid provision) the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of protein synthesis, translocates toward the cell periphery. However, it is unknown if mTORC1-mediated phosphorylation events occur in these peripheral regions or prior to translocation (i.e. in central regions). We therefore aimed to determine the cellular location of a mTORC1-mediated phosphorylation event, RPS6Ser240/244, in human skeletal muscle following anabolic stimuli. Fourteen young, healthy males either ingested a protein-carbohydrate beverage (0.25g/kg protein, 0.75g/kg carbohydrate) alone (n=7;23±5yrs;76.8±3.6kg;13.6±3.8%BF, FED) or following a whole-body resistance exercise bout (n=7;22±2yrs;78.1±3.6kg;12.2±4.9%BF, EXFED). Vastus lateralis muscle biopsies were obtained at rest (PRE) and 120 and 300min following anabolic stimuli. RPS6Ser240/244 phosphorylation measured by immunofluorescent staining or immunoblot was positively correlated (r=0.76, p<0.001). Peripheral staining intensity of p-RPS6Ser240/244 increased above PRE in both FED and EXFED at 120min (~54% and ~138% respectively, p<0.05) but was greater in EXFED at both post-stimuli time points (p<0.05). The peripheral-central ratio of p-RPS6240/244 staining displayed a similar pattern, even when corrected for total RPS6 distribution, suggesting RPS6 phosphorylation occurs to a greater extent in the periphery of fibers. Moreover, p-RPS6Ser240/244 intensity within paxillin-positive regions, a marker of focal adhesion complexes, was elevated at 120min irrespective of stimulus (p=0.006) before returning to PRE at 300min. These data confirm that RPS6Ser240/244 phosphorylation occurs in the region of human muscle fibers to which mTOR translocates following anabolic stimuli and identifies focal adhesion complexes as a potential site of mTORC1 regulation in vivo.

Pro- and macroglycogenolysis: relationship with exercise intensity and duration

2001 ◽  
Vol 90 (3) ◽  
pp. 873-879 ◽  
Author(s):  
T. E. Graham ◽  
K. B. Adamo ◽  
J. Shearer ◽  
I. Marchand ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Regulation ◽  
Human Skeletal Muscle ◽  
Exercise Period ◽  
Group 3 ◽  
Group 2 ◽  
Male Subjects ◽  
Muscle Biopsies ◽  
Over Time ◽  
Group 1

We examined the net catabolism of two pools of glycogen, proglycogen (PG) and macroglycogen (MG), in human skeletal muscle during exercise. Male subjects ( n = 21) were assigned to one of three groups. Group 1 exercised 45 min at 70% maximal O2 uptake (V˙o 2 max) and had muscle biopsies at rest, 15 min, and 45 min. Group 2 exercised at 85%V˙o 2 max to exhaustion (45.4 ± 3.4 min) and had biopsies at rest, 10 min, and exhaustion. Group 3 performed three 3-min bouts of exercise at 100%V˙o 2 max separated by 6 min of rest. Biopsies were taken at rest and after each bout. Group 1 had small MG and PG net glycogenolysis rates (ranging from 3.8 ± 1.0 to 2.4 ± 0.6 mmol glucosyl units · kg−1 · min−1) that did not change over time. In group 2, the MG glycogenolysis rate remained low and unchanged over time, whereas the PG rate was initially elevated (11.3 ± 2.3 mmol glucosyl units · kg−1 · min−1) and declined ( P ≤ 0.05) with time. During the first 10 min, PG concentration ([PG]) declined ( P ≤ 0.05), whereas MG concentration ([MG]) did not. Similarly, in group 3, in both the first and the second bouts of exercise [PG] declined ( P ≤ 0.05) and [MG] did not, although by the end of the second exercise period the [MG] was lower ( P ≤ 0.05) than the rest level. The net catabolic rates for PG in the first two exercises were 22.6 ± 6.8 and 21.8 ± 8.2 mmol glucosyl units · kg−1 · min−1, whereas the corresponding values for MG were 17.6 ± 6.0 and 10.8 ± 5.6. The MG pool appeared to be more resistant to mobilization, and, when activated, its catabolism was inhibited more rapidly than that of PG. This suggests that the metabolic regulation of the two pools must be different.

Glycogen depletion patterns in human skeletal muscle fibers during prolonged work

1973 ◽  
Vol 344 (1) ◽  
pp. 1-12 ◽  
Author(s):  
P. D. Gollnick ◽  
R. B. Armstrong ◽  
C. W. Saubert ◽  
W. L. Sembrowich ◽  
R. E. Shepherd ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Muscle Fibers ◽  
Glycogen Depletion ◽  
Skeletal Muscle Fibers

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 Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuo Wang ◽  
Bonnie Seaberg ◽  
Ximena Paez-Colasante ◽  
Mendell Rimer
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptor ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Neuromuscular Synapse ◽  
Fiber Morphology ◽  
Skeletal Muscle Fibers ◽  
Slow Twitch

Abstract To test the role of extracellular-signal regulated kinases 1 and 2 (ERK1/2) in slow-twitch, type 1 skeletal muscle fibers, we studied the soleus muscle in mice genetically deficient for myofiber ERK1/2. Young adult mutant soleus was drastically wasted, with highly atrophied type 1 fibers, denervation at most synaptic sites, induction of “fetal” acetylcholine receptor gamma subunit (AChRγ), reduction of “adult” AChRε, and impaired mitochondrial biogenesis and function. In weanlings, fiber morphology and mitochondrial markers were mostly normal, yet AChRγ upregulation and AChRε downregulation were observed. Synaptic sites with fetal AChRs in weanling muscle were ~3% in control and ~40% in mutants, with most of the latter on type 1 fibers. These results suggest that: (1) ERK1/2 are critical for slow-twitch fiber growth; (2) a defective γ/ε-AChR subunit switch, preferentially at synapses on slow fibers, precedes wasting of mutant soleus; (3) denervation is likely to drive this wasting, and (4) the neuromuscular synapse is a primary subcellular target for muscle ERK1/2 function in vivo.

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