Identification of Potentially Related Genes and Mechanisms Involved in Skeletal Muscle Atrophy Induced by Excessive Exercise in Zebrafish

Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein–protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.

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

Marine Drugs ◽

10.3390/md17050284 ◽

2019 ◽

Vol 17 (5) ◽

pp. 284 ◽

Cited By ~ 4

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.

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

Cell and Tissue Research ◽

10.1007/s00441-020-03251-4 ◽

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

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

Experimental Animals ◽

10.1538/expanim.20-0046 ◽

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

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

Frontiers in Physiology ◽

10.3389/fphys.2020.580223 ◽

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.

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Resveratrol attenuates skeletal muscle atrophy induced by chronic kidney disease via MuRF1 signaling pathway

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.04.022 ◽

2017 ◽

Vol 487 (1) ◽

pp. 83-89 ◽

Cited By ~ 14

Author(s):

Li-Jing Sun ◽

Yan-Ni Sun ◽

Shun-Jie Chen ◽

Shuang Liu ◽

Geng-Ru Jiang

Keyword(s):

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Signaling Pathway ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy

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Histone Deacetylase 2 Suppresses Skeletal Muscle Atrophy and Senescence via NF-κB Signaling Pathway in Cigarette Smoke-Induced Mice with Emphysema

International Journal of Chronic Obstructive Pulmonary Disease ◽

10.2147/copd.s314640 ◽

2021 ◽

Vol Volume 16 ◽

pp. 1661-1675

Author(s):

Chao Li ◽

Zhaohui Deng ◽

Guixian Zheng ◽

Ting Xie ◽

Xinyan Wei ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Histone Deacetylase ◽

Cigarette Smoke ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy ◽

Histone Deacetylase 2

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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 ◽

10.3390/nu12092729 ◽

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.

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