scholarly journals Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Joo Wan Kim ◽  
Sae-Kwang Ku ◽  
Ki Young Kim ◽  
Sung Goo Kim ◽  
Min Ho Han ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Atrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Activity Levels ◽  
Protective Effects ◽  
Sciatic Neurectomy ◽  
Antioxidant Defense Systems ◽  
Antioxidant Effects

The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects andviaan increase in protein synthesis and a decrease in protein degradation.

A Clinically Relevant Decrease in Contractile Force Differentially Regulates Control of Glucocorticoid Receptor Translocation in Mouse Skeletal Muscle

2021 ◽  
Author(s):  
Kirsten R. Dunlap ◽  
Jennifer L. Steiner ◽  
Michael L. Rossetti ◽  
Scot R. Kimball ◽  
Bradley S. Gordon
Keyword(s):  
Protein Synthesis ◽  
Glucocorticoid Receptor ◽  
Resistance Exercise ◽  
Muscle Atrophy ◽  
Nuclear Translocation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Contractile Force ◽  
Force Generation ◽  
Protein Balance

Muscle atrophy decreases physical function and overall health. Increased glucocorticoid production and/or use of prescription glucocorticoids can significantly induce muscle atrophy by activating the glucocorticoid receptor thereby transcribing genes that shift protein balance in favor of net protein degradation. While mechanical overload can blunt glucocorticoid-induced atrophy in young muscle, those affected by glucocorticoids generally have impaired force generation. It is unknown whether contractile force alters the ability of resistance exercise to mitigate glucocorticoid receptor translocation and induce a desirable shift in protein balance when glucocorticoids are elevated. In the present study, mice were subjected to a single bout of unilateral, electrically induced muscle contractions by stimulating the sciatic nerve at 100 Hz or 50 Hz frequencies to elicit high force or moderate force contractions of the tibialis anterior, respectively. Dexamethasone was used to activate the glucocorticoid receptor. Dexamethasone increased glucocorticoid signaling, including nuclear translocation of the receptor, but this was mitigated only by high force contractions. The ability of high force contractions to mitigate glucocorticoid receptor translocation coincided with a contraction-mediated increase in muscle protein synthesis, which did not occur in the dexamethasone treated mice subjected to moderate force contractions. Though moderate force contractions failed to increase protein synthesis following dexamethasone treatment, both high and moderate force contractions blunted the glucocorticoid-mediated increase in LC3 II:I marker of autophagy. Thus, these data show that force generation is important for the ability of resistance exercise to mitigate glucocorticoid receptor translocation and promote a desirable shift in protein balance when glucocorticoids are elevated.

scholarly journals Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

1998 ◽  
Vol 156 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D Dardevet ◽  
C Sornet ◽  
I Savary ◽  
E Debras ◽  
P Patureau-Mirand ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Adult Rats ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

scholarly journals Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2724 ◽  
Author(s):  
Hyejin Lee ◽  
Ji-Won Heo ◽  
A-Reum Kim ◽  
Minson Kweon ◽  
Sorim Nam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Inflammatory Responses ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Janus Kinase ◽  
Skeletal Muscle Atrophy ◽  
E3 Ligases

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world’s most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

scholarly journals Comparison of protein synthesis and degradation in incubated and perfused muscle

1983 ◽  
Vol 212 (3) ◽  
pp. 649-653 ◽  
Author(s):  
A S Clark ◽  
W E Mitch
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Insulin Treatment ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Protein Degradation ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Rates of muscle protein synthesis and degradation measured in the perfused hindquarter were compared with those in incubated epitrochlearis muscles. With fed or starved mature rats, results without insulin treatment were identical. With insulin treatment, protein synthesis in perfused hindquarters was greater, though protein degradation was the same. Thus rates of muscle protein degradation estimated by these two methods in vitro correspond closely.

scholarly journals Nutritional and endocrinological manipulation of lean deposition in forage-fed steers

1991 ◽  
Vol 66 (2) ◽  
pp. 171-185 ◽  
Author(s):  
J. M. Dawson ◽  
P. J. Buttery ◽  
M. J. Lammiman ◽  
J. B. Soar ◽  
C. P. Essex ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Lipid Composition ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Live Weight ◽  
Dry Matter Content ◽  
Semitendinosus Muscle ◽  
Intramuscular Lipid

The effect of supplementing grass silage with fishmeal on growth, muscle composition and the rate of muscle protein synthesis was investigated in young Friesian steers with and without oestradiol implants. The effect of the β-adrenergic agonist cimaterol was simultaneously investigated in animals fed on silage alone. Treatments lasted for 9 or 10 weeks. Fishmeal supplementation significantly increased animal growth rates (P < 0.001) and the weights of three dissected muscles (P < 0.001) compared with the silage-fed controls. These effects were further enhanced in animals also implanted with oestradiol. Muscle weights expressed as a proportion of body-weight were increased by fishmeal, suggesting that protein deposition had been enhanced. No further increase in the proportional muscle weights was obtained with oestradiol. Muscle dry matter content tended to be increased in both implanted and non-implanted animals receiving fishmeal compared with controls, but the proportions of protein, fat and ash were relatively constant. The intramuscular lipid composition was slightly altered by fishmeal. Muscle protein fractional synthetic rates (FSR), measured by continuous infusion of [3H]tyrosine, were increased by fishmeal in all three muscles of both implanted and non-implanted animals. There were no differences, however, due to oestradiol, over non-implanted fishmeal animals. This suggests that oestradiol may increase muscle accretion by reducing protein degradation rate. Cimaterol significantly increased longissimus dorsi (P < 0.05) and vastus lateralis (P < 0.01) muscle weights but had no effect on semitendinosus muscle weight or live-weight gain. The proportion of protein was increased (P <0.001) and the fat content reduced (P < 0.05) in all three muscles but intramuscular lipid composition was not markedly affected. Whilst methylhistidine: creatinine excretion was reduced by cimaterol, FSR were increased in the I. dorsi and v. lateralis muscles suggesting β-agonists have effects on both protein synthesis and protein degradation.

Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

2013 ◽  
Vol 305 (1) ◽  
pp. L82-L91 ◽  
Author(s):  
Chiel C. de Theije ◽  
Ramon C. J. Langen ◽  
Wouter H. Lamers ◽  
Annemie M. W. J. Schols ◽  
S. Eleonore Köhler
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Food Intake ◽  
Protein Degradation ◽  
Muscle Atrophy ◽  
Protein Turnover ◽  
Chronic Hypoxia ◽  
Muscle Protein ◽  
Specific Component ◽  
Regulatory Pathways

The balance of muscle protein synthesis and degradation determines skeletal muscle mass. We hypothesized that hypoxia-induced muscle atrophy and alterations in the regulation of muscle protein turnover include a hypoxia-specific component, in addition to the observed effects of reduction in food intake in response to hypoxia. Mice were subjected to normoxic, hypoxic (8% oxygen), or pair-fed conditions for 2, 4, and 21 days. Cell-autonomous effects of hypoxia on skeletal muscle were also assessed in differentiated C2C12 myotubes. Hypoxia induced an initial rapid loss of body and muscle weight, which remained decreased during chronic hypoxia and could only in part be explained by the hypoxia-induced reduction of food intake (semistarvation). Regulatory steps of protein synthesis (unfolded protein response and mammal target of rapamycin signaling) remained active in response to acute and sustained hypoxia but not to semistarvation. Activation of regulatory signals for protein degradation, including increased expression of Murf1, Atrogin-1, Bnip3, and Map1lc3b mRNAs, was observed in response to acute hypoxia and to a lesser extent following semistarvation. Conversely, the sustained elevation of Atrogin-1, Bnip3, and Map1lc3b mRNAs and the increased activity of their upstream transcriptional regulator Forkhead box O1 were specific to chronic hypoxia because they were not observed in response to reduced food intake. In conclusion, altered regulation of protein turnover during hypoxia-induced muscle atrophy resulted from an interaction of semistarvation and a hypoxia-specific component. The finding that food restriction but not hypoxia-induced semistarvation inhibited regulatory steps in protein synthesis suggests a hypoxia-specific impairment of the coordination between protein-synthesis signaling and protein-degradation signaling in skeletal muscle.

Protein and amino acid metabolism in posterior hemicorpus of acutely uremic rats

1983 ◽  
Vol 244 (6) ◽  
pp. E615-E623 ◽  
Author(s):  
R. M. Flugel-Link ◽  
I. B. Salusky ◽  
M. R. Jones ◽  
J. D. Kopple
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Protein Degradation ◽  
Alkaline Protease ◽  
Cathepsin D ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Creatine Phosphate ◽  
Net Uptake ◽  
Nonessential Amino Acids

Protein synthesis and degradation and net uptake and release of amino acids and minerals were examined in the perfused hemicorpus of bilaterally nephrectomized and sham-operated control rats. Animals were studied 30 h after surgery. In comparison with controls, uremic rats had greater urea N appearance (net urea generation) and lower plasma and muscle concentrations of most amino acids. Muscle protein synthesis was not altered, but protein degradation was greater in uremic versus sham rats. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. ATP, creatine phosphate, cAMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in muscles of the uremic versus sham rats. Thus, in acutely uremic rats there is increased protein wasting in the hemicorpus due to enhanced protein degradation. The enhanced protein degradation does not appear to be due to increased muscle cathepsin B1, cathepsin D, or alkaline protease activities.

scholarly journals Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1970 ◽  
Author(s):  
Tadashi Yoshida ◽  
Patrice Delafontaine
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Atrophy ◽  
Muscle Regeneration ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Atrophy

Insulin-like growth factor-1 (IGF-1) is a key growth factor that regulates both anabolic and catabolic pathways in skeletal muscle. IGF-1 increases skeletal muscle protein synthesis via PI3K/Akt/mTOR and PI3K/Akt/GSK3β pathways. PI3K/Akt can also inhibit FoxOs and suppress transcription of E3 ubiquitin ligases that regulate ubiquitin proteasome system (UPS)-mediated protein degradation. Autophagy is likely inhibited by IGF-1 via mTOR and FoxO signaling, although the contribution of autophagy regulation in IGF-1-mediated inhibition of skeletal muscle atrophy remains to be determined. Evidence has suggested that IGF-1/Akt can inhibit muscle atrophy-inducing cytokine and myostatin signaling via inhibition of the NF-κΒ and Smad pathways, respectively. Several miRNAs have been found to regulate IGF-1 signaling in skeletal muscle, and these miRs are likely regulated in different pathological conditions and contribute to the development of muscle atrophy. IGF-1 also potentiates skeletal muscle regeneration via activation of skeletal muscle stem (satellite) cells, which may contribute to muscle hypertrophy and/or inhibit atrophy. Importantly, IGF-1 levels and IGF-1R downstream signaling are suppressed in many chronic disease conditions and likely result in muscle atrophy via the combined effects of altered protein synthesis, UPS activity, autophagy, and muscle regeneration.

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