scholarly journals Serum Creatinine as a Potential Biomarker of Skeletal Muscle Atrophy in Non-small Cell Lung Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Willian das Neves ◽  
Christiano R. R. Alves ◽  
Ana Paula de Souza Borges ◽  
Gilberto de Castro
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Serum Creatinine ◽  
Muscle Atrophy ◽  
Normal Serum ◽  
Skeletal Muscle Atrophy ◽  
Cross Sectional ◽  
Tissue Area ◽  
Nsclc Patients ◽  
Low Serum

Objectives: Identifying simple biomarkers to determine muscle atrophy in non-small-cell lung cancer (NSCLC) patients remains a critical research gap. Since creatinine is mainly a product from intramuscular creatine metabolism, we tested the hypothesis that low serum creatinine levels would be associated to skeletal muscle atrophy in NSCLC patients.Materials and Methods: This is a prospective cohort study including 106 treatment-naive patients with histologically confirmed stage IV NSCLC. All patients performed routine serum creatinine laboratory tests. We divided patients into two groups based on low (<0.7 mg/dL for male and <0.5 mg/dL for female) or normal creatinine levels. We compared body mass index (BMI), psoas muscle cross-sectional area, adipose tissue area and complete blood counts between groups.Results: Male and female NSCLC patients with low serum creatinine levels had low muscle cross-sectional area as compared to patients with normal serum creatinine levels. Male NSCLC patients with low serum creatinine also displayed reduced BMI, reduced adipose tissue area, and elevated systemic inflammation compared to NSCLC patients with normal serum creatinine levels. There were no significant differences between female groups for BMI, adipose tissue area and inflammatory markers.Conclusions: Serum creatinine is a potential prognostic biomarker of skeletal muscle atrophy in NSCLC patients. Since serum creatinine is a simple and accessible measurement, we suggest that it should be monitored in longitudinal follow-up of NSCLC patients as a biomarker of 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.

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.

scholarly journals The TWEAK–Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice

2010 ◽  
Vol 188 (6) ◽  
pp. 833-849 ◽  
Author(s):  
Ashwani Mittal ◽  
Shephali Bhatnagar ◽  
Akhilesh Kumar ◽  
Estelle Lach-Trifilieff ◽  
Sandrine Wauters ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Fiber Type ◽  
Nuclear Factor Κb ◽  
Skeletal Muscle Atrophy ◽  
Muscle Proteins ◽  
Cross Sectional ◽  
Transgenic Expression ◽  
Genetic Ablation ◽  
Skeletal Muscle Wasting

Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor–inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor κB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK–Fn14 system is an important target for preventing skeletal muscle wasting.

scholarly journals Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3267 ◽  
Author(s):  
Chun Chen ◽  
Jai-Sing Yang ◽  
Chi-Cheng Lu ◽  
Yu-Jen Chiu ◽  
Hung-Che Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Fruits And Vegetables ◽  
Cell Injury ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Protective Effects ◽  
Cross Sectional ◽  
Hydroxyl Free Radical ◽  
C2c12 Skeletal Muscle Cells

Glucocorticoids are widely used anti-inflammatory drugs in clinical settings. However, they can induce skeletal muscle atrophy by reducing fiber cross-sectional area and myofibrillar protein content. Studies have proven that antioxidants can improve glucocorticoid-induced skeletal muscle atrophy. Quercetin is a potent antioxidant flavonoid widely distributed in fruits and vegetables and has shown protective effects against dexamethasone-induced skeletal muscle atrophy. In this study, we demonstrated that dexamethasone significantly inhibited cell growth and induced cell apoptosis by stimulating hydroxyl free radical production in C2C12 skeletal muscle cells. Our results evidenced that quercetin increased C2C12 skeletal cell viability and exerted antiapoptotic effects on dexamethasone-treated C2C12 cells by regulating mitochondrial membrane potential (ΔΨm) and reducing oxidative species. Quercetin can protect against dexamethasone-induced muscle atrophy by regulating the Bax/Bcl-2 ratio at the protein level and abnormal ΔΨm, which leads to the suppression of apoptosis.

scholarly journals HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenjing Ma ◽  
Yong Cai ◽  
Yuntian Shen ◽  
Xin Chen ◽  
Lilei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Underlying Mechanism ◽  
Skeletal Muscle Atrophy ◽  
Regulation Mechanism ◽  
Type I ◽  
Muscle Adaptation ◽  
Cross Sectional

Denervation can activate the catabolic pathway in skeletal muscle and lead to progressive skeletal muscle atrophy. At present, there is no effective treatment for muscle atrophy. Histone deacetylase 4 (HDAC4) has recently been found to be closely related to muscle atrophy, but the underlying mechanism of HDAC4 in denervation-induced muscle atrophy have not been described clearly yet. In this study, we found that the expression of HDAC4 increased significantly in denervated skeletal muscle. HDAC4 inhibition can effectively diminish denervation-induced muscle atrophy, reduce the expression of muscle specific E3 ubiquitin ligase (MuRF1 and MAFbx) and autophagy related proteins (Atg7, LC3B, PINK1 and BNIP3), inhibit the transformation of type I fibers to type II fibers, and enhance the expression of SIRT1 and PGC-1 α. Transcriptome sequencing and bioinformatics analysis was performed and suggested that HDAC4 may be involved in denervation-induced muscle atrophy by regulating the response to denervation involved in the regulation of muscle adaptation, cell division, cell cycle, apoptotic process, skeletal muscle atrophy, and cell differentiation. STRING analysis showed that HDAC4 may be involved in the process of muscle atrophy by directly regulating myogenin (MYOG), cell cycle inhibitor p21 (CDKN1A) and salt induced kinase 1 (SIK1). MYOG was significantly increased in denervated skeletal muscle, and MYOG inhibition could significantly alleviate denervation-induced muscle atrophy, accompanied by the decreased MuRF1 and MAFbx. MYOG overexpression could reduce the protective effect of HDAC4 inhibition on denervation-induced muscle atrophy, as evidenced by the decreased muscle mass and cross-sectional area of muscle fibers, and the increased mitophagy. Taken together, HDAC4 inhibition can alleviate denervation-induced muscle atrophy by reducing MYOG expression, and HDAC4 is also directly related to CDKN1A and SIK1 in skeletal muscle, which suggests that HDAC4 inhibitors may be a potential drug for the treatment of neurogenic muscle atrophy. These results not only enrich the molecular regulation mechanism of denervation-induced muscle atrophy, but also provide the experimental basis for HDAC4-MYOG axis as a new target for the prevention and treatment of muscular atrophy.

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 Investigation of niclosamide as a repurposing agent for skeletal muscle atrophy

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252135
Author(s):  
Hyun-Jun Kim ◽  
Ji-Hyung Lee ◽  
Seon-Wook Kim ◽  
Sang-Hoon Lee ◽  
Da-Woon Jung ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Cancer Metastasis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Atrophy ◽  
Differentiation Markers ◽  
Cross Sectional

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle.

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.

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