scholarly journals Protein Supplementation Enhances the Effects of Intermittent Loading on Skeletal Muscles by Activating the mTORC1 Signaling Pathway in a Rat Model of Disuse Atrophy

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2729
Author(s):  
Sho Miyatake ◽  
Kazuo Hino ◽  
Yuko Natsui ◽  
Goro Ebisu ◽  
Satoshi Fujita
Keyword(s):  
Skeletal Muscle ◽  
Ribosomal Protein ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Gastrocnemius Muscle ◽  
Protein Supplementation ◽  
Skeletal Muscle Atrophy ◽  
Ribosomal Protein S6 ◽  
Mtorc1 Signaling ◽  
Gastrocnemius Muscles

Inactivity leads to skeletal muscle atrophy, whereas intermittent loading (IL) during hind limb unloading (HU) attenuates muscle atrophy. However, the combined effects of IL and protein supplementation on disuse muscle atrophy are unclear. Therefore, we investigated the effects of IL and a high-protein oral nutritional supplement (HP) during HU on skeletal muscle mass and protein synthesis/breakdown. Male F344 rats were assigned to the control (CON), 14-day HU (HU), IL during HU (HU + IL), and IL during HU followed by HP administration (2.6 g protein/kg/day; HU + IL + HP) groups. Soleus and gastrocnemius muscles were sampled 30 min after the last IL and HP supplementation. HU decreased relative soleus and gastrocnemius muscle masses. Relative muscle masses and p70 ribosomal protein S6 kinase/ribosomal protein S6 phosphorylation in soleus and gastrocnemius muscles were higher in the HU + IL group than the HU group and further higher in the HU + IL + HP group than the HU + IL group in gastrocnemius muscle. Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

scholarly journals PO-242 Effects of tail suspension on the expression of FNDC5/Irisin protein in rat skeletal muscle

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Junzhi Sun ◽  
Qiang Jiang
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Muscle Atrophy ◽  
Muscle Fiber ◽  
Soleus Muscle ◽  
Gastrocnemius Muscle ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Tail Suspension ◽  
Gastrocnemius Muscles

Objective Irisin is a myokine secreted by skeletal muscle,and it is a type I membrane protein factor encoded by the protein 5(FNDC5) gene after cleavage and modification of the type III fibronectin component.Dependence of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α).In this study, the potential association between skeletal muscle atrophy and irisin was explored by detecting changes in rat soleus and gastrocnemius irisin-related proteins during unloading. Methods Twenty male 8-week rats were randomly divided into control group C (n=10) and suspension group T (n=10). The tail suspension system (TSS) was used to perform a 2-week tail suspension experiment on the T group. Two weeks after the tail suspension test, the weights of the rats and the wet weights of soleus and gastrocnemius muscles were measured. HE staining was performed under light microscope to observe the changes of muscle fiber area of skeletal muscle in each group. Western-blot was used to detect the protein expression of MURF1, PGC-1α and FNDC5 in soleus muscle and gastrocnemius muscle of each group. Results (1) The soleus muscle and gastrocnemius muscle mass in T group decreased by 28.6% (P<0.05) and 25.8% (P<0.01), respectively. (2) The cross-sectional area of soleus muscle and gastrocnemius muscle fiber in T group decreased by 20.5% (P<0.01) and 25.2% (P<0.05), respectively. (3) The MURF1 protein expression in the gastrocnemius muscle and soleus muscle in the T group was significantly higher than that in the C group (P<0.01). (4) The expression of PGC-1α protein in gastrocnemius muscle and soleus muscle of T group was significantly lower than that in group C (P<0.05). (5) The expression of FNDC5 protein in gastrocnemius muscle and soleus muscle in T group was significantly lower than that in group C (P<0.05). Conclusions After sole tail suspension for two weeks, the soleus and gastrocnemius muscles of the rats were obviously atrophied, and soleus muscle atrophy was more obvious. Skeletal muscle atrophy may be related to increased expression of MURF1. The decrease of FNDC5/Irisin content may be related to the occurrence of skeletal muscle atrophy, and PGC-1α also may be involved in this process.

scholarly journals Protective Effect of Pyropia yezoensis Peptide on Dexamethasone-Induced Myotube Atrophy in C2C12 Myotubes

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 284 ◽  
Author(s):  
Min-Kyeong Lee ◽  
Jeong-Wook Choi ◽  
Youn Hee Choi ◽  
Taek-Jeong Nam
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Protective Effects ◽  
Factor I ◽  
Igf I ◽  
Foxo Signaling Pathway

Dexamethasone (DEX), a synthetic glucocorticoid, causes skeletal muscle atrophy. This study examined the protective effects of Pyropia yezoensis peptide (PYP15) against DEX-induced myotube atrophy and its association with insulin-like growth factor-I (IGF-I) and the Akt/mammalian target of rapamycin (mTOR)-forkhead box O (FoxO) signaling pathway. To elucidate the molecular mechanisms underlying the effects of PYP15 on DEX-induced myotube atrophy, C2C12 myotubes were treated for 24 h with 100 μM DEX in the presence or absence of 500 ng/mL PYP15. Cell viability assays revealed no PYP15 toxicity in C2C12 myotubes. PYP15 activated the insulin-like growth factor-I receptor (IGF-IR) and Akt-mTORC1 signaling pathway in DEX-induced myotube atrophy. In addition, PYP15 markedly downregulated the nuclear translocation of transcription factors FoxO1 and FoxO3a, and inhibited 20S proteasome activity. Furthermore, PYP15 inhibited the autophagy-lysosomal pathway in DEX-stimulated myotube atrophy. Our findings suggest that PYP15 treatment protected against myotube atrophy by regulating IGF-I and the Akt-mTORC1-FoxO signaling pathway in skeletal muscle. Therefore, PYP15 treatment appears to exert protective effects against skeletal muscle atrophy.

ISLR regulates skeletal muscle atrophy via IGF1-PI3K/Akt-Foxo signaling pathway

2020 ◽  
Vol 381 (3) ◽  
pp. 479-492
Author(s):  
Can Cui ◽  
Shunshun Han ◽  
Xiaoxu Shen ◽  
Haorong He ◽  
Yuqi Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Foxo Signaling Pathway

scholarly journals KLF5 regulates chicken skeletal muscle atrophy via the canonical Wnt/β-catenin signaling pathway

2020 ◽  
Vol 69 (4) ◽  
pp. 430-440
Author(s):  
Dong-Hao ZHANG ◽  
Hua-Dong YIN ◽  
Jing-Jing LI ◽  
Yan WANG ◽  
Chao-Wu YANG ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Canonical Wnt ◽  
Chicken Skeletal Muscle

scholarly journals Ficus carica L. Attenuates Denervated Skeletal Muscle Atrophy via PPARα/NF-κB Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Junxi Dai ◽  
Yaoxian Xiang ◽  
Da Fu ◽  
Lei Xu ◽  
Junjian Jiang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Peripheral Nerve ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Muscle Atrophy ◽  
Peripheral Nerve Injury ◽  
Ficus Carica ◽  
Differentially Expressed ◽  
Skeletal Muscle Atrophy ◽  
Denervated Muscle

Treatment options for denervated skeletal muscle atrophy are limited, in part because the underlying molecular mechanisms are not well understood. Unlike previous transcriptomics studies conducted in rodent models of peripheral nerve injury, in the present study, we performed high-throughput sequencing with denervated atrophic biceps muscle and normal (non-denervated) sternocleidomastoid muscle samples obtained from four brachial plexus injury (BPI) patients. We also investigated whether Ficus carica L. (FCL.) extract can suppress denervated muscle atrophy in a mouse model, along with the mechanism of action. We identified 1471 genes that were differentially expressed between clinical specimens of atrophic and normal muscle, including 771 that were downregulated and 700 that were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed genes were mainly enriched in the GO terms “structural constituent of muscle,” “Z disc,” “M band,” and “striated muscle contraction,” as well as “Cell adhesion molecules,” “Glycolysis/Gluconeogenesis,” “Peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway,” and “P53 signaling pathway.” In experiments using mice, the reduction in wet weight and myofiber diameter in denervated muscle was improved by FCL. extract compared to saline administration, which was accompanied by downregulation of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Moreover, although both denervated groups showed increased nuclear factor (NF)-κB activation and PPARα expression, the degree of NF-κB activation was lower while PPARα and inhibitor of NF-κB IκBα expression was higher in FCL. extract-treated mice. Thus, FCL. extract suppresses denervation-induced inflammation and attenuates muscle atrophy by enhancing PPARα expression and inhibiting NF-κB activation. These findings suggest that FCL. extract has therapeutic potential for preventing denervation-induced muscle atrophy caused by peripheral nerve injury or disease.

scholarly journals Hyperglycemia Inhibits Recovery From Disuse-Induced Skeletal Muscle Atrophy in Rats

2014 ◽  
pp. 465-474 ◽  
Author(s):  
H. KATAOKA ◽  
J. NAKANO ◽  
Y. MORIMOTO ◽  
Y. HONDA ◽  
J. SAKAMOTO ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cross Sections ◽  
Serum Insulin ◽  
Recovery Period ◽  
Diabetic Rats ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Ankle Joints ◽  
Gastrocnemius Muscles

The purpose of this study was to evaluate the effects of hyperglycemia on skeletal muscle recovery following disuse-induced muscle atrophy in rats. Wistar rats were grouped as streptozotocin-induced diabetic rats and non-diabetic rats. Both ankle joints of each rat were immobilized to induce atrophy of the gastrocnemius muscles. After two weeks of immobilization and an additional two weeks of recovery, tail blood and gastrocnemius muscles were isolated. Serial cross sections of muscles were stained for myosin ATPase (pH 4.5) and alkaline phosphatase activity. Serum insulin and muscle insulin-like growth factor-1 (IGF-1) levels were also measured. Serum insulin levels were significantly reduced in the diabetic rats compared to the non-diabetic controls. The diameters of type I, IIa, and IIb myofibers and capillary-to-myofiber ratio in the isolated muscle tissue were decreased after immobilization in both treatments. During the recovery period, these parameters were restored in the non-diabetic rats, but not in the diabetic rats. In addition, muscle IGF-1 levels after recovery increased significantly in the non-diabetic rats, but not in the diabetic rats. We conclude that decreased levels of insulin and IGF-1 and impairment of angiogenesis associated with diabetes might be partly responsible for the inhibition of regrowth in diabetic muscle.

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

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.

scholarly journals Ubiquitin E3 ligases Atrogin-1 and MuRF1 protein contents are differentially regulated in the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 myotubes

2021 ◽  
Author(s):  
Yusuke Nishimura ◽  
Ibrahim Musa ◽  
Peter Dawson ◽  
Lars Holm ◽  
Yu-Chiang Lai
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Signaling Pathway ◽  
Negative Regulator ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Gene Expressions ◽  
E3 Ligases ◽  
Gene And Protein Expression ◽  
Mtorc1 Signaling

Muscle-specific ubiquitin E3 ligases, Atrogin-1 and MuRF1, are highly expressed in multiple conditions of skeletal muscle atrophy. The PI3K/Akt/FoxO signaling pathway is well known to regulate Atrogin-1 and MuRF1 gene expressions. Evidence supporting this is largely based on stimuli by insulin and IGF-1, that activate anabolic signaling, including Akt and Akt-dependent transcription factors. However, Akt activation also activates the mammalian target of rapamycin complex 1 (mTORC1) which induces skeletal muscle hypertrophy. However, whether mTORC1-dependent signaling has a role in regulating Atrogin-1 and/or MuRF1 gene and protein expression is currently unclear. In this study, we confirmed that activation of insulin-mediated Akt signaling suppresses both Atrogin-1 and MuRF1 protein content and that inhibition of Akt increases both Atrogin-1 and MuRF1 protein content in C2C12 myotubes. Interestingly, inhibition of mTORC1 using a specific mTORC1 inhibitor, rapamycin, increased Atrogin-1, but not MuRF1, protein content. Furthermore, activation of AMP-activated protein kinase (AMPK), a negative regulator of the mTORC1 signaling pathway, also showed distinct time-dependent changes between Atrogin-1 and MuRF1 protein content, suggesting differential regulatory mechanisms between Atrogin-1 and MuRF1 protein content. To further explore the downstream of mTORC1 signaling, we employed a specific S6K1 inhibitor, PF-4708671, and found that Atrogin-1 protein content was dose-dependently increased with PF-4708671 treatment, whereas MuRF1 protein content was not significantly altered. Overall, our results indicate that Atrogin-1 and MuRF1 protein contents are regulated by different mechanisms, the downstream of Akt, and that Atrogin-1 protein content can be regulated by rapamycin-sensitive mTOR-S6K1 dependent signaling pathway.

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