scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

scholarly journals Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome

2020 ◽  
Vol 129 (2) ◽  
pp. 272-282 ◽  
Author(s):  
Sue C. Bodine
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Single Gene ◽  
Skeletal Muscle Atrophy ◽  
Protein Breakdown ◽  
E3 Ligases ◽  
The Past

Skeletal muscle atrophy continues to be a serious consequence of many diseases and conditions for which there is no treatment. Our understanding of the mechanisms regulating skeletal muscle mass has improved considerably over the past two decades. For many years it was known that skeletal muscle atrophy resulted from an imbalance between protein synthesis and protein breakdown, with the net balance shifting toward protein breakdown. However, the molecular and cellular mechanisms underlying the increased breakdown of myofibrils was unknown. Over the past two decades, numerous reports have identified novel genes and signaling pathways that are upregulated and activated in response to stimuli such as disuse, inflammation, metabolic stress, starvation and others that induce muscle atrophy. This review summarizes the discovery efforts performed in the identification of several pathways involved in the regulation of skeletal muscle mass: the mammalian target of rapamycin (mTORC1) and the ubiquitin proteasome pathway and the E3 ligases, MuRF1 and MAFbx. While muscle atrophy is a common outcome of many diseases, it is doubtful that a single gene or pathway initiates or mediates the breakdown of myofibrils. Interestingly, however, is the observation that upregulation of the E3 ligases, MuRF1 and MAFbx, is a common feature of many divergent atrophy conditions. The challenge for the field of muscle biology is to understand how all of the various molecules, transcription factors, and signaling pathways interact to produce muscle atrophy and to identify the critical factors for intervention.

Activation of the CRF 2 receptor modulates skeletal muscle mass under physiological and pathological conditions

2003 ◽  
Vol 285 (4) ◽  
pp. E889-E898 ◽  
Author(s):  
Richard T. Hinkle ◽  
Elizabeth Donnelly ◽  
David B. Cody ◽  
Steven Samuelsson ◽  
Jana S. Lange ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Nerve Damage ◽  
Skeletal Muscle Atrophy ◽  
Function Loss ◽  
Selective Agonists ◽  
And Function ◽  
First Time

Two receptors activated by the corticotropin-releasing factor (CRF) family of peptides have been identified, the CRF 1 receptor (CRF1R) and the CRF 2 receptor (CRF2R). Of these, the CRF2R is expressed in skeletal muscle. To understand the role of the CRF2R in skeletal muscle, we utilized CRFR knockout mice and CRF2R-selective agonists to modulate nerve damage and corticosteroid- and disuse-induced skeletal muscle atrophy in mice. These analyses demonstrated that activation of the CRF2R decreased nerve damage and corticosteroid- and disuse-induced skeletal muscle mass and function loss. In addition, selective activation of the CRF2R increased nonatrophy skeletal muscle mass. Thus we describe for the first time a novel activity of the CRF2R, modulation of skeletal muscle mass.

Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force

2005 ◽  
Vol 98 (2) ◽  
pp. 655-662 ◽  
Author(s):  
Richard T. Hinkle ◽  
Elizabeth Donnelly ◽  
David B. Cody ◽  
Russell J. Sheldon ◽  
Robert J. Isfort
Keyword(s):  
Skeletal Muscle ◽  
Vasoactive Intestinal Peptide ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Skeletal Muscle Atrophy ◽  
Physiological Control ◽  
Corticosteroid Administration ◽  
Skeletal Muscle Wasting ◽  
Selective Agonist

Of the two known vasoactive intestinal peptide receptors (VPAC1R and VPAC2R), the VPAC2R is expressed in skeletal muscle. To evaluate the function of the VPAC2R in the physiological control of skeletal muscle mass, we utilized the VPAC1R selective agonist [K15,R16,L27]VIP(1-7) GRF(8-27)-NH2 and the VPAC2R selective agonist Ro-25-1553 to treat mice and rats undergoing either nerve damage-, corticosteroid-, or disuse-induced skeletal muscle atrophy. These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles. These studies indicate that VPAC2R agonists may have utility for the treatment of skeletal muscle-wasting diseases.

Maintenance of muscle mass is not dependent on the calcineurin-NFAT pathway

2002 ◽  
Vol 282 (6) ◽  
pp. C1387-C1395 ◽  
Author(s):  
Esther E. Dupont-Versteegden ◽  
Micheal Knox ◽  
Cathy M. Gurley ◽  
John D. Houlé ◽  
Charlotte A. Peterson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Muscle Size ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
Activated T Cells ◽  
Beneficial Effects ◽  
The Face ◽  
Calcineurin Activity

In this study, the role of the calcineurin pathway in skeletal muscle atrophy and atrophy-reducing interventions was investigated in rat soleus muscles. Because calcineurin has been suggested to be involved in skeletal and cardiac muscle hypertrophy, we hypothesized that blocking calcineurin activity would eliminate beneficial effects of interventions that maintain muscle mass in the face of atrophy-inducing stimuli. Hindlimb suspension and spinal cord transection were used to induce atrophy, and intermittent reloading and exercise were used to reduce atrophy. Cyclosporin (CsA, 25 mg · kg−1 · day−1) was administered to block calcineurin activity. Soleus muscles were studied 14 days after the onset of atrophy. CsA administration did not inhibit the beneficial effects of the two muscle-maintaining interventions, nor did it change muscle mass in control or atrophied muscles, suggesting that calcineurin does not play a role in regulating muscle size during atrophy. However, calcineurin abundance was increased in atrophied soleus muscles, and this was associated with nuclear localization of NFATc1 (a nuclear factor of activated T cells). Therefore, results suggest that calcineurin may be playing opposing roles during skeletal muscle atrophy and under muscle mass-maintaining conditions.

scholarly journals Swim training affects Akt signaling and ameliorates loss of skeletal muscle mass in a mouse model of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karol Cieminski ◽  
Damian Jozef Flis ◽  
Katarzyna Dzik ◽  
Jan Jacek Kaczor ◽  
Emilia Czyrko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Tibialis Anterior Muscle ◽  
Akt Signaling ◽  
The Body ◽  
Skeletal Muscle Atrophy ◽  
Akt Signaling Pathway

AbstractWe tested the hypothesis that swim training reverses the impairment of Akt/FOXO3a signaling, ameliorating muscle atrophy in ALS mice. Transgenic male mice B6SJL-Tg (SOD1G93A) 1Gur/J were used as the ALS model (n = 35), with wild-type B6SJL (WT) mice as controls (n = 7). ALS mice were analyzed before ALS onset, at ALS onset, and at terminal ALS. Levels of insulin/Akt signaling pathway proteins were determined, and the body and tibialis anterior muscle mass and plasma creatine kinase. Significantly increased levels of FOXO3a in ALS groups (from about 13 to 21-fold) compared to WT mice were observed. MuRF1 levels in the ONSET untrained group (12.0 ± 1.7 AU) were significantly higher than in WT mice (1.12 ± 0.2 AU) and in the BEFORE ALS group (3.7 ± 0.9 AU). This was associated with body mass and skeletal muscle mass reduction. Swim training significantly ameliorated the reduction of skeletal muscle mass in both TERMINAL groups (p < 0.001) and partially reversed changes in the levels of Akt signaling pathway proteins. These findings shed light on the swimming-induced attenuation of skeletal muscle atrophy in ALS with possible practical implications for anti-cachexia approaches.

scholarly journals Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 323
Author(s):  
Jiling Liang ◽  
Hu Zhang ◽  
Zhengzhong Zeng ◽  
Liangwen Wu ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Exercise ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Critical Role ◽  
Treadmill Running ◽  
Skeletal Muscle Atrophy

Sarcopenia is an aging-induced syndrome characterized by a progressive reduction of skeletal muscle mass and strength. Increasing evidence has attested that appropriate and scientific exercise could induce autophagy or optimize the functional status of autophagy, which plays a critical role in senescent muscular dystrophy. As a publicly recognized strategy for extending lifespan and improving the health of the elderly, the underlying mechanisms of lifelong regular aerobic exercise for the prevention of sarcopenia have not been fully elucidated. To explore the role of lifelong aerobic exercise in the beneficial regulation of autophagic signaling pathways in senescent skeletal muscle, the natural aging mice were used as the sarcopenia model and subjected to lifelong treadmill running to evaluate corresponding parameters related to skeletal muscle atrophy and autophagic signaling pathways. Compared with the young control mice, the aged mice showed a significant reduction in skeletal muscle mass, gastrocnemius muscle weight/body weight (GMW/BW) ratio, and cross-sectional areas (CSA) of skeletal muscle fibers (p < 0.01). In contrast, lifelong aerobic exercise effectively rescued these reduced biomarkers associated with muscle atrophy. Moreover, as shown in the activated AMPK/PGC-1α signaling pathway, lifelong aerobic exercise successfully prevented the aging-induced impairment of the ubiquitin-proteasome system (UPS), excessive apoptosis, defective autophagy, and mitochondrial dysfunction. The exercise-induced autophagy suppressed the key regulatory components of the UPS, inhibited excessive apoptosis, and optimized mitochondrial quality control, thereby preventing and delaying aging-induced skeletal muscle atrophy.

scholarly journals Tail suspension is useful as a sarcopenia model in rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Akira Nemoto ◽  
Toru Goyagi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Experimental Model ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Whole Body ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

High altitude mediated skeletal muscle atrophy: Protective role of curcumin

Biochimie ◽  
2019 ◽  
Vol 156 ◽  
pp. 138-147 ◽  
Author(s):  
Pooja Chaudhary ◽  
Yogendra Kumar Sharma ◽  
Shivani Sharma ◽  
Som Nath Singh ◽  
Geetha Suryakumar
Keyword(s):  
Skeletal Muscle ◽  
High Altitude ◽  
Muscle Atrophy ◽  
Protective Role ◽  
Skeletal Muscle Atrophy

Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin

2003 ◽  
Vol 285 (4) ◽  
pp. E876-E888 ◽  
Author(s):  
Suzanne Reisz-Porszasz ◽  
Shalender Bhasin ◽  
Jorge N. Artaza ◽  
Ruoqing Shen ◽  
Indrani Sinha-Hikim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Fluorescent Protein ◽  
Male Mice ◽  
Wild Type ◽  
Specific Expression ◽  
Muscle Weight ◽  
Myostatin Gene

Mutations in the myostatin gene are associated with hypermuscularity, suggesting that myostatin inhibits skeletal muscle growth. We postulated that increased tissue-specific expression of myostatin protein in skeletal muscle would induce muscle loss. To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA. Transgenic mice harboring these MCK promoters linked to enhanced green fluorescent protein (EGFP) expressed the reporter protein only in skeletal and cardiac muscles (MCK) or in skeletal muscle alone (MCK-3E). Seven-week-old animals were genotyped by PCR of tail DNA or by Southern blot analysis of liver DNA. Myostatin mRNA and protein, measured by RT-PCR and Western blot, respectively, were significantly higher in gastrocnemius, quadriceps, and tibialis anterior of MCK/Mst-transgenic mice compared with wild-type mice. Male MCK/Mst-transgenic mice had 18–24% lower hind- and forelimb muscle weight and 18% reduction in quadriceps and gastrocnemius fiber cross-sectional area and myonuclear number (immunohistochemistry) than wild-type male mice. Male transgenic mice with mutated MCK-3E promoter showed similar effects on muscle mass. However, female transgenic mice with either type of MCK promoter did not differ from wild-type controls in either body weight or skeletal muscle mass. In conclusion, increased expression of myostatin in skeletal muscle is associated with lower muscle mass and decreased fiber size and myonuclear number, decreased cardiac muscle mass, and increased fat mass in male mice, consistent with its role as an inhibitor of skeletal muscle mass. The mechanism of gender specificity remains to be clarified.

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