scholarly journals Deletion of NAD(P)H Oxidase 2 Prevents Angiotensin II-Induced Skeletal Muscle Atrophy

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tomoyasu Kadoguchi ◽  
Shingo Takada ◽  
Takashi Yokota ◽  
Takaaki Furihata ◽  
Junichi Matsumoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Angiotensin Ii ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Akt Phosphorylation ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Skeletal muscle atrophy is induced by an imbalance between protein synthesis and degradation. Our previous studies reported that angiotensin II (AII) directly induced muscle atrophy in mice. This study investigated the role of NAD(P)H oxidase 2 (Nox2) activation by AII in the induction of skeletal muscle atrophy. For 4 weeks, either saline (vehicle: V) or AII (1000 ng kg−1 min−1) was infused into male wild-type (WT) and Nox2 knockout (KO) mice via osmotic minipumps. Experiments were performed in the following 4 groups: WT + V, KO + V, WT + AII, and KO + AII. Body weight, muscle weight, and myocyte cross-sectional area were significantly decreased in WT + AII compared to WT + V mice, and these changes were not observed in KO + AII mice. Akt phosphorylation of Ser473 and p70S6K of Thr389 was decreased, gene expression levels of MuRF-1 and atrogin-1 were increased in WT + AII compared to WT + V, and these changes were significantly attenuated in KO + AII mice. The deletion of Nox2 prevented AII-induced skeletal muscle atrophy via improving the balance between protein synthesis and degradation. Therefore, Nox2 may be a therapeutic target for AII-induced skeletal muscle atrophy.

scholarly journals A time course for markers of protein synthesis and degradation with hindlimb unloading and the accompanying anabolic resistance to refeeding

2020 ◽  
Vol 129 (1) ◽  
pp. 36-46 ◽  
Author(s):  
Paul A. Roberson ◽  
Kevin L. Shimkus ◽  
Jaclyn E. Welles ◽  
Dandan Xu ◽  
Abigale L. Whitsell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Time Course ◽  
Hindlimb Unloading ◽  
Skeletal Muscle Atrophy ◽  
Anabolic Resistance ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Hindlimb unloading causes significant skeletal muscle atrophy by adversely affecting the balance between protein synthesis and breakdown. This study demonstrates a more complete time course for changes in biomarkers associated with protein synthesis and breakdown and investigates the associated anabolic resistance to an anabolic stimulus following hindlimb unloading. These data in concert with information from other studies provide a basis for designing future experiments to optimally interrogate a desired cellular biomarker or pathway.

scholarly journals Serum extracellular vesicle miR-203a-3p content is associated with skeletal muscle mass and protein turnover during disuse atrophy and regrowth

2020 ◽  
Vol 319 (2) ◽  
pp. C419-C431
Author(s):  
Douglas W. Van Pelt ◽  
Ivan J. Vechetti ◽  
Marcus M. Lawrence ◽  
Kathryn L. Van Pelt ◽  
Parth Patel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Weight Bearing ◽  
Mirna Content ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Small noncoding microRNAs (miRNAs) are important regulators of skeletal muscle size, and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy and its associated systemic effects. The purpose of this study was to understand how muscle atrophy and regrowth alter in vivo serum EV miRNA content. We also associated changes in serum EV miRNA with protein synthesis, protein degradation, and miRNA within muscle, kidney, and liver. We subjected adult (10 mo) F344/BN rats to three conditions: weight bearing (WB), hindlimb suspension (HS) for 7 days to induce muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR). Microarray analysis of EV miRNA content showed that the overall changes in serum EV miRNA were predicted to target major anabolic, catabolic, and mechanosensitive pathways. MiR-203a-3p was the only miRNA demonstrating substantial differences in HS EVs compared with WB. There was a limited association of EV miRNA content to the corresponding miRNA content within the muscle, kidney, or liver. Stepwise linear regression demonstrated that EV miR-203a-3p was correlated with muscle mass and muscle protein synthesis and degradation across all conditions. Finally, EV miR-203a-3p expression was significantly decreased in human subjects who underwent unilateral lower limb suspension (ULLS) to induce muscle atrophy. Altogether, we show that serum EV miR-203a-3p expression is related to skeletal muscle protein turnover and atrophy. We suggest that serum EV miR-203a-3p content may be a useful biomarker and future work should investigate whether serum EV miR-203a-3p content is mechanistically linked to protein synthesis and degradation.

Angiotensin-(1–7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism

2014 ◽  
Vol 128 (5) ◽  
pp. 307-319 ◽  
Author(s):  
Franco Cisternas ◽  
María Gabriela Morales ◽  
Carla Meneses ◽  
Felipe Simon ◽  
Enrique Brandan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Muscle Atrophy ◽  
Membrane Receptor ◽  
Skeletal Muscle Atrophy ◽  
Akt Phosphorylation ◽  
Mas Receptor ◽  
Plasma Membrane Receptor ◽  
Dependent Mechanism

Angiotensin-(1–7) produces an anti-atrophic effect in our model of skeletal muscle atrophy induced by angiotensin II, which is mediated by its plasma membrane receptor Mas. Angiotensin-(1–7) exerts its anti-atrophic effects, at least, by inducing AKT phosphorylation.

scholarly journals Dicer-mediated miRNA processing is not involved in controlling muscle mass during muscle atrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satoshi Oikawa ◽  
Jaehoon Shin ◽  
Takao Akama ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Molecular Networks ◽  
Adult Skeletal Muscle ◽  
Functional Roles ◽  
Denervated Muscles ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

AbstractMuscle atrophy occurs in a variety of physiological and pathological conditions. Specific molecular networks that govern protein synthesis and degradation play important roles in controlling muscle mass under diverse catabolic states. MicroRNAs (miRNAs) were previously found to be regulators of protein synthesis and degradation, and their expressions in skeletal muscle were altered in muscle wasting conditions. However, functional roles of miRNAs in muscle atrophy are poorly understood. In this study, we generated tamoxifen-inducible Dicer knockout (iDicer KO) mice and subjected them to 2 weeks of single hindlimb denervation. The expression of Dicer mRNA was significantly reduced in muscle of the iDicer KO mice compared to that of WT mice. The loss of Dicer moderately reduced levels of muscle-enriched miRNAs, miR-1, miR-133a and miR-206 in both innervated and denervated muscles of the iDicer KO mice. We also found that the extent of denervation-induced muscle atrophy as well as changes of signaling molecules related to protein synthesis/degradation pathways in the iDicer KO mice were comparable to these in WT mice. Taken together, Dicer knockout in adult skeletal muscle did not affect denervation-induced muscle atrophy.

scholarly journals Antioxidant Activity of Valeriana fauriei Protects against Dexamethasone-Induced Muscle Atrophy

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Young In Kim ◽  
Hyunjung Lee ◽  
Farida S. Nirmala ◽  
Hyo-Deok Seo ◽  
Tae Youl Ha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
High Dose ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Myosin Heavy Chain Isoform ◽  
Ros Scavenger

Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction

2021 ◽  
Author(s):  
Feng Li-Li ◽  
Li Bo-Wen ◽  
Xi Yue ◽  
Tian Zhen-Jun ◽  
Cai Meng-Xin
Keyword(s):  
Myocardial Infarction ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Aerobic Exercise ◽  
Muscle Atrophy ◽  
Cell Apoptosis ◽  
Exercise Group ◽  
Skeletal Muscle Atrophy ◽  
Akt Pathway

Objectives: Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Materials and Methods: Male C57/BL6 mice were used to establish the MI model and divided into three groups: sedentary MI group, MI with aerobic exercise group and MI with resistance exercise group, sham-operated group was used as control. Exercise-trained animals were subjected to four-weeks of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis and degradation and cell apoptosis in gastrocnemius muscle were detected. And H2O2-treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1R inhibitor NVP-AEW541 and PI3K inhibitor LY294002 to explore the mechanism. Results：Exercises up-regulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling, increased the expressions of Pax7, myogenic regulatory factors (MRFs) and protein synthesis, reduced protein degradation and cell apoptosis in MI-mice. In vitro, IGF-1 up-regulated the levels of Pax7 and MRFs, mTOR and P70S6K, reduced MuRF1, MAFbx and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. Conclusion: AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation and cells apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt pathway.

Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats

2001 ◽  
Vol 281 (1) ◽  
pp. C179-C187 ◽  
Author(s):  
Troy A. Hornberger ◽  
R. Bridge Hunter ◽  
Susan C. Kandarian ◽  
Karyn A. Esser
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Translation ◽  
Hindlimb Unloading ◽  
Initiation Factor ◽  
Skeletal Muscle Atrophy ◽  
Α Subunit ◽  
Translation Factors ◽  
Ribosomal S6 Kinase

In the rat, denervation and hindlimb unloading are two commonly employed models used to study skeletal muscle atrophy. In these models, muscle atrophy is generally produced by a decrease in protein synthesis and an increase in protein degradation. The decrease in protein synthesis has been suggested to occur by an inhibition at the level of protein translation. To better characterize the regulation of protein translation, we investigated the changes that occur in various translation initiation and elongation factors. We demonstrated that both hindlimb unloading and denervation produce alterations in the phosphorylation and/or total amount of the 70-kDa ribosomal S6 kinase, eukaryotic initiation factor 2 α-subunit, and eukaryotic elongation factor 2. Our findings indicate that the regulation of these protein translation factors differs between the models of atrophy studied and between the muscles evaluated (e.g., soleus vs. extensor digitorum longus).

scholarly journals β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2180
Author(s):  
Mari Noguchi ◽  
Tomoya Kitakaze ◽  
Yasuyuki Kobayashi ◽  
Katsuyuki Mukai ◽  
Naoki Harada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Skeletal Muscle Atrophy ◽  
Related Factor ◽  
Related Factors ◽  
Cross Sectional ◽  
Senescence Accelerated Mouse

We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

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