The estrous cycle and skeletal muscle atrophy: Investigations in rodent models of muscle loss

: Skeletal muscle atrophy has been characterizedas a state of uncontrolled inflammation and oxidative stress that escalates the protein catabolism. Recent advancement supportsthat impinging signaling molecules in the muscle fibers controlled throughtoll-like receptors (TLR). Activated TLR signalingpathways have been identified as inhibitors of muscle mass and provoke the settings for muscle atrophy. Among them, mainly TLR2 and TLR4 manifest their presence to exacerbate the release of the pro-inflammatory cytokine to deform the synchronized muscle programming. The present review enlightens the TLR signaling mediated muscle loss and their interplay betweeninflammationand skeletal muscle growth.

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MERG1A Protein Abundance Increases in the Atrophied Skeletal Muscle of Denervated Mice, But Does Not Affect NFκB Activity

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlab062 ◽

2021 ◽

Author(s):

Luke B Anderson ◽

Barbara Ravara ◽

Sohaib Hameed ◽

Chase D Latour ◽

Sawyer M Latour ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Gastrocnemius Muscle ◽

Ectopic Expression ◽

Dominant Negative ◽

Skeletal Muscle Atrophy ◽

K Channel ◽

Protein Abundance ◽

Muscle Loss ◽

Ubiquitin Proteasome

Abstract Skeletal muscle atrophy may occur with disease, injury, decreased muscle use, starvation, and normal aging. No reliably effective treatments for atrophy are available, thus research into the mechanisms contributing to muscle loss is essential. The ERG1A K+ channel contributes to muscle loss by increasing ubiquitin proteasome proteolysis (UPP) in the skeletal muscle of both unweighted and cachectic mice. Because the mechanisms which produce atrophy vary based upon the initiating factor, here we investigate atrophy produced by denervation. Using immunohistochemistry and immunoblots, we demonstrate that ERG1A protein abundance increases significantly in the Gastrocnemius muscle of rodents 7 days after both sciatic nerve transection and hind limb unweighting. Further, we reveal that ectopic expression of a Merg1a encoded plasmid in normal mouse Gastrocnemius muscle has no effect on activity of the NFκB transcription factor family, a group of proteins which contribute to muscle atrophy by modulation of the UPP. Further, although NFκB activity increases significantly after denervation, we show that expression of a plasmid encoding a dominant negative Merg1a mutant in Gastrocnemius muscle prior to denervation, has no effect on NFκB activity. Thus, although the ERG1A K+ channel increases UPP, it does not do so through modulation of NFκB transcription factors.

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Skeletal muscle proteolysis in response to short-term unloading in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.90558.2008 ◽

2008 ◽

Vol 105 (3) ◽

pp. 902-906 ◽

Cited By ~ 81

Author(s):

Per A. Tesch ◽

Ferdinand von Walden ◽

Thomas Gustafsson ◽

Richard M. Linnehan ◽

Todd A. Trappe

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Simulated Microgravity ◽

Skeletal Muscle Atrophy ◽

Muscle Loss ◽

Short Term ◽

Promising Tool ◽

Muscle Disuse ◽

Naturally Occurring ◽

Muscle Contractile

Skeletal muscle atrophy is evident after muscle disuse, unloading, or spaceflight and results from decreased protein content as a consequence of decreased protein synthesis, increased protein breakdown or both. At this time, there are essentially no human data describing proteolysis in skeletal muscle undergoing atrophy on Earth or in space, primarily due to lack of valid and accurate methodology. This particular study aimed at assessing the effects of short-term unloading on the muscle contractile proteolysis rate. Eight men were subjected to 72-h unilateral lower limb suspension (ULLS) and intramuscular interstitial levels of the naturally occurring proteolytic tracer 3-methylhistidine (3MH) were measured by means of microdialysis before and on completion of this intervention. The 3MH concentration following 72-h ULLS (2.01 ± 0.22 nmol/ml) was 44% higher ( P < 0.05) than before ULLS (1.56 ± 0.20 nmol/ml). The present experimental model and the employed method determining 3MH in microdialysates present a promising tool for monitoring skeletal muscle proteolysis or metabolism of specific muscles during conditions resulting in atrophy caused by, e.g., disuse and real or simulated microgravity. This study provides evidence that the atrophic processes are evoked rapidly and within 72 h of unloading and suggests that countermeasures should be employed in the early stages of space missions to offset or prevent muscle loss during the period when the rate of muscle atrophy is the highest.

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Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00487.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. E363-E371 ◽

Cited By ~ 219

Author(s):

Kun Ma ◽

Con Mallidis ◽

Shalender Bhasin ◽

Vahid Mahabadi ◽

Jorge Artaza ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Muscle Atrophy ◽

Muscular Atrophy ◽

Day Treatment ◽

Negative Regulator ◽

Skeletal Muscle Atrophy ◽

Muscle Loss ◽

Myostatin Gene ◽

Dose Dependent

The mechanisms by which excessive glucocorticoids cause muscular atrophy remain unclear. We previously demonstrated that dexamethasone increases the expression of myostatin, a negative regulator of skeletal muscle mass, in vitro. In the present study, we tested the hypothesis that dexamethasone-induced muscle loss is associated with increased myostatin expression in vivo. Daily administration (60, 600, 1,200 μg/kg body wt) of dexamethasone for 5 days resulted in rapid, dose-dependent loss of body weight (-4.0, -13.4, -17.2%, respectively, P < 0.05 for each comparison), and muscle atrophy (6.3, 15.0, 16.6% below controls, respectively). These changes were associated with dose-dependent, marked induction of intramuscular myostatin mRNA (66.3, 450, 527.6% increase above controls, P < 0.05 for each comparison) and protein expression (0.0, 260.5, 318.4% increase above controls, P < 0.05). We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent. When dexamethasone treatment (600 μg · kg-1 · day-1) was extended from 5 to 10 days, the rate of body weight loss was markedly reduced to ∼2% within this extended period. The concentrations of intramuscular myosin heavy chain type II in dexamethasone-treated rats were significantly lower (-43% after 5-day treatment, -14% after 10-day treatment) than their respective corresponding controls. The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level. Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy. We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway.

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