Glucocorticoid sites in skeletal muscle: adrenalectomy, maturation, fiber type, and sex

1984 ◽  
Vol 247 (1) ◽  
pp. E118-E125 ◽  
Author(s):  
D. C. DuBois ◽  
R. R. Almon
Keyword(s):  
Skeletal Muscle ◽  
Extensor Digitorum Longus ◽  
Fiber Type ◽  
Cross Reactivity ◽  
Tissue Preparation ◽  
Stabilization Method ◽  
Exponential Decline ◽  
Longus Muscle ◽  
Slow Fiber ◽  
Fast Fiber

The glucocorticoid receptor population in skeletal muscle of the rat was examined. Data are included that address the following: tissue preparation, receptor stabilization, method of assay and analysis, cross-reactivity of a large variety of steroids, time to equilibrium, and the effect of adrenalectomy on the number of sites as well as the apparent binding affinity. In addition, we have observed the following: 1) an exponential decline in the concentration of sites from 27 to 160 days after birth; 2) a significantly higher concentration of sites in muscle from male animals as compared with female animals; and 3) a significantly higher concentration of sites in the slow-fiber soleus muscle as compared with the fast-fiber extensor digitorum longus muscle.

scholarly journals Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle

2005 ◽  
Vol 168 (6) ◽  
pp. 887-897 ◽  
Author(s):  
Yewei Liu ◽  
William R. Randall ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Histone Deacetylases ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Adult Skeletal Muscle ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Dependent Protein ◽  
Nuclear Levels ◽  
Activity Dependent

Class II histone deacetylases (HDACs) may decrease slow muscle fiber gene expression by repressing myogenic transcription factor myocyte enhancer factor 2 (MEF2). Here, we show that repetitive slow fiber type electrical stimulation, but not fast fiber type stimulation, caused HDAC4-GFP, but not HDAC5-GFP, to translocate from the nucleus to the cytoplasm in cultured adult skeletal muscle fibers. HDAC4-GFP translocation was blocked by calmodulin-dependent protein kinase (CaMK) inhibitor KN-62. Slow fiber type stimulation increased MEF2 transcriptional activity, nuclear Ca2+ concentration, and nuclear levels of activated CaMKII, but not total nuclear CaMKII or CaM-YFP. Thus, calcium transients for slow, but not fast, fiber stimulation patterns appear to provide sufficient Ca2+-dependent activation of nuclear CaMKII to result in net nuclear efflux of HDAC4. Nucleocytoplasmic shuttling of HDAC4-GFP in unstimulated resting fibers was not altered by KN-62, but was blocked by staurosporine, indicating that different kinases underlie nuclear efflux of HDAC4 in resting and stimulated muscle fibers.

scholarly journals Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload

2017 ◽  
Vol 313 (2) ◽  
pp. C154-C161 ◽  
Author(s):  
Val A. Fajardo ◽  
Bradley A. Rietze ◽  
Paige J. Chambers ◽  
Catherine Bellissimo ◽  
Eric Bombardier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Ectopic Expression ◽  
Oxidative Capacity ◽  
Adaptive Responses ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Fiber Number ◽  
Type Shift ◽  
Calcineurin Signaling

Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses, we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln-null ( Sln−/−) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles. In the WT overloaded plantaris, we observed ectopic expression of SLN, myofiber hypertrophy, increased fiber number, and a fast-to-slow fiber type shift, which were associated with increased calcineurin signaling (NFAT dephosphorylation and increased stabilin-2 protein content) and reduced SERCA activity. In the WT tenotomized soleus, we observed a 14-fold increase in SLN protein, myofiber atrophy, decreased fiber number, and a slow-to-fast fiber type shift, which were also associated with increased calcineurin signaling and reduced SERCA activity. Genetic deletion of Sln altered these physiological outcomes, with the overloaded plantaris myofibers failing to grow in size and number, and transition towards the slow fiber type, while the unloaded soleus muscles exhibited greater reductions in fiber size and number, and an accelerated slow-to-fast fiber type shift. In both the Sln−/− overloaded and unloaded muscles, these findings were associated with elevated SERCA activity and blunted calcineurin signaling. Thus, SLN plays an important role in adaptive muscle remodeling potentially through calcineurin stimulation, which could have important implications for other muscle diseases and conditions.

scholarly journals Identification in skeletal muscle of a distinct extracellular pool of amino acids, and its role in protein synthesis

1971 ◽  
Vol 121 (5) ◽  
pp. 817-827 ◽  
Author(s):  
R. C. Hider ◽  
E. B. Fern ◽  
D. R. London
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Incubation Medium ◽  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Longus Muscle ◽  
Kinetics Of

1. The kinetics of radioactive labelling of extra- and intra-cellular amino acid pools and protein of the extensor digitorum longus muscle were studied after incubations with radioactive amino acids in vitro. 2. The results indicated that an extracellular pool could be defined, the contents of which were different from those of the incubation medium. 3. It was concluded that amino acids from the extracellular pool, as defined in this study, were incorporated directly into protein.

scholarly journals Purine biosynthesis de novo in rat skeletal muscle

1983 ◽  
Vol 216 (3) ◽  
pp. 605-610 ◽  
Author(s):  
T G Sheehan ◽  
E R Tully
Keyword(s):  
Skeletal Muscle ◽  
Extensor Digitorum Longus ◽  
De Novo ◽  
Adenine Nucleotides ◽  
Extensor Digitorum ◽  
Purine Biosynthesis ◽  
Rat Skeletal Muscle ◽  
Purine Synthesis ◽  
Longus Muscle ◽  
Isolated Rat

Purine biosynthesis by the ‘de novo’ pathway was demonstrated in isolated rat extensor digitorum longus muscle with [1-14C]glycine, [3-14C]serine and sodium [14C]formate as nucleotide precursors. Evidence is presented which suggests that the source of glycine and serine for purine biosynthesis is extracellular rather than intracellular. The relative incorporation rates of the three precursors were formate greater than glycine greater than serine. Over 85% of the label from formate and glycine was recovered in the adenine nucleotides, principally ATP. Azaserine markedly inhibited purine biosynthesis from both formate and glycine. Cycloserine inhibited synthesis from serine, but not from formate. Adenine, hypoxanthine and adenosine markedly inhibited purine synthesis from sodium [14C]formate.

scholarly journals Calcineurin Is Necessary for the Maintenance but Not Embryonic Development of Slow Muscle Fibers

2005 ◽  
Vol 25 (15) ◽  
pp. 6629-6638 ◽  
Author(s):  
Misook Oh ◽  
Igor I. Rybkin ◽  
Victoria Copeland ◽  
Michael P. Czubryt ◽  
John M. Shelton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Oxidative Capacity ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Specific Expression ◽  
Interacting Protein ◽  
Type Composition ◽  
Slow Fiber ◽  
Fast Twitch

ABSTRACT Skeletal muscles are a mosaic of slow and fast twitch myofibers. During embryogenesis, patterns of fiber type composition are initiated that change postnatally to meet physiological demand. To examine the role of the protein phosphatase calcineurin in the initiation and maintenance of muscle fiber types, we used a “Flox-ON” approach to obtain muscle-specific overexpression of the modulatory calcineurin-interacting protein 1 (MCIP1/DSCR1), an inhibitor of calcineurin. Myo-Cre transgenic mice with early skeletal muscle-specific expression of Cre recombinase were used to activate the Flox-MCIP1 transgene. Contractile components unique to type 1 slow fibers were absent from skeletal muscle of adult Myo-Cre/Flox-MCIP1 mice, whereas oxidative capacity, myoglobin content, and mitochondrial abundance were unaltered. The soleus muscles of Myo-Cre/Flox-MCIP1 mice fatigued more rapidly than the wild type as a consequence of the replacement of the slow myosin heavy chain MyHC-1 with a fast isoform, MyHC-2A. MyHC-1 expression in Myo-Cre/Flox-MCIP1 embryos and early neonates was normal. These results demonstrate that developmental patterning of slow fibers is independent of calcineurin, while the maintenance of the slow-fiber phenotype in the adult requires calcineurin activity.

Myosin light chain phosphorylation-dephosphorylation in mammalian skeletal muscle

1982 ◽  
Vol 242 (3) ◽  
pp. C234-C241 ◽  
Author(s):  
D. R. Manning ◽  
J. T. Stull
Keyword(s):  
Skeletal Muscle ◽  
Light Chain ◽  
Extensor Digitorum Longus ◽  
Myosin Light Chain ◽  
Extensor Digitorum Longus Muscle ◽  
Extensor Digitorum ◽  
Mammalian Skeletal Muscle ◽  
Phosphate Content ◽  
Longus Muscle ◽  
Fast Twitch

Phosphorylation of the myosin light chain 2 (LC2) subunit was examined in rat fast-twitch and slow-twitch skeletal muscles in response to repetitive stimulation at 23 and 35 degrees C and on incubation of fast-twitch skeletal muscle with isoproterenol. After a 1-s tetany at 35 degrees C, LC2 phosphate content in extensor digitorum longus muscle increased rapidly and transiently from 0.21 to 0.51 mol phosphate/mol LC2. This pattern of phosphorylation was similar to that observed at 23 degrees C. Increases in LC2 phosphate content were dependent on the frequency and duration of stimulation. In soleus muscle LC2 phosphate content was minimal following a 1-s tetany but increased markedly following more prolonged tetanies. On incubation of extensor digitorum longus muscle with isoproterenol (20 microM), LC2 phosphate content did not change, whereas phosphorylase a levels increased. A positive correlation existed between LC2 phosphate content and potentiation of peak twitch tension in both types of muscles, suggesting a physiological function for LC2 phosphorylation.

scholarly journals Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading

2009 ◽  
Vol 297 (1) ◽  
pp. C6-C16 ◽  
Author(s):  
Clay E. Pandorf ◽  
Fadia Haddad ◽  
Carola Wright ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
Gene Regulation ◽  
Myosin Heavy Chain ◽  
Histone Modifications ◽  
Heavy Chain ◽  
Fiber Type ◽  
Histone H3 ◽  
Mhc Genes ◽  
Slow Fiber ◽  
Muscle Unloading

Recent advances in chromatin biology have enhanced our understanding of gene regulation. It is now widely appreciated that gene regulation is dependent upon post-translational modifications to the histones which package genes in the nucleus of cells. Active genes are known to be associated with acetylation of histones (H3ac) and trimethylation of lysine 4 in histone H3 (H3K4me3). Using chromatin immunoprecipitation (ChIP), we examined histone modifications at the myosin heavy chain (MHC) genes expressed in fast vs. slow fiber-type skeletal muscle, and in a model of muscle unloading, which results in a shift to fast MHC gene expression in slow muscles. Both H3ac and H3K4me3 varied directly with the transcriptional activity of the MHC genes in fast fiber-type plantaris and slow fiber-type soleus. During MHC transitions with muscle unloading, histone H3 at the type I MHC becomes de-acetylated in correspondence with down-regulation of that gene, while upregulation of the fast type IIx and IIb MHCs occurs in conjunction with enhanced H3ac in those MHCs. Enrichment of H3K4me3 is also increased at the type IIx and IIb MHCs when these genes are induced with muscle unloading. Downregulation of IIa MHC, however, was not associated with corresponding loss of H3ac or H3K4me3. These observations demonstrate the feasibility of using the ChIP assay to understand the native chromatin environment in adult skeletal muscle, and also suggest that the transcriptional state of types I, IIx and IIb MHC genes are sensitive to histone modifications both in different muscle fiber-types and in response to altered loading states.

scholarly journals Heat Treatment Inhibits Skeletal Muscle Atrophy of Glucocorticoid-Induced Myopathy in Rats

2015 ◽  
pp. 897-905 ◽  
Author(s):  
Y. MORIMOTO ◽  
Y. KONDO ◽  
H. KATAOKA ◽  
Y. HONDA ◽  
R. KOZU ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Muscle Fiber ◽  
Wistar Rats ◽  
Extensor Digitorum Longus ◽  
Fiber Diameter ◽  
Skeletal Muscle Atrophy ◽  
Longus Muscle

The purpose of this study was to investigate the influence of heat treatment on glucocorticoid (GC)-induced myopathy. Eight-week-old Wistar rats were randomly assigned to the control, Dex, and Dex + Heat groups. Dexamethasone (2 mg/kg) was injected subcutaneously 6 days per week for 2 weeks in the Dex and Dex + Heat group. In the Dex + Heat group, heat treatment was performed by immersing hindlimbs in water at 42 °C for 60 min, once every 3 days for 2 weeks. The extensor digitorum longus muscle was extracted following 2 weeks of experimentation. In the Dex + Heat group, muscle fiber diameter, capillary/muscle fiber ratio, and level of heat shock protein 72 were significantly higher and atrogene expression levels were significantly lower than in the Dex group. Our results suggest that heat treatment inhibits the development of GC-induced myopathy by decreasing atrogene expression and increasing angiogenesis.

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