scholarly journals Absence of Desmin Results in Impaired Adaptive Response to Mechanical Overloading of Skeletal Muscle

2021 ◽  
Vol 9 ◽  
Author(s):  
Pierre Joanne ◽  
Yeranuhi Hovhannisyan ◽  
Maximilien Bencze ◽  
Marie-Thérèse Daher ◽  
Ara Parlakian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Adaptive Response ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Muscle Growth ◽  
Clinical Manifestations ◽  
Plantaris Muscle ◽  
Surgical Ablation ◽  
Control Muscle

Background: Desmin is a muscle-specific protein belonging to the intermediate filament family. Desmin mutations are linked to skeletal muscle defects, including inherited myopathies with severe clinical manifestations. The aim of this study was to examine the role of desmin in skeletal muscle remodeling and performance gain induced by muscle mechanical overloading which mimics resistance training.Methods: Plantaris muscles were overloaded by surgical ablation of gastrocnemius and soleus muscles. The functional response of plantaris muscle to mechanical overloading in desmin-deficient mice (DesKO, n = 32) was compared to that of control mice (n = 36) after 7-days or 1-month overloading. To elucidate the molecular mechanisms implicated in the observed partial adaptive response of DesKO muscle, we examined the expression levels of genes involved in muscle growth, myogenesis, inflammation and oxidative energetic metabolism. Moreover, ultrastructure and the proteolysis pathway were explored.Results: Contrary to control, absolute maximal force did not increase in DesKO muscle following 1-month mechanical overloading. Fatigue resistance was also less increased in DesKO as compared to control muscle. Despite impaired functional adaptive response of DesKO mice to mechanical overloading, muscle weight and the number of oxidative MHC2a-positive fibers per cross-section similarly increased in both genotypes after 1-month overloading. However, mechanical overloading-elicited remodeling failed to activate a normal myogenic program after 7-days overloading, resulting in proportionally reduced activation and differentiation of muscle stem cells. Ultrastructural analysis of the plantaris muscle after 1-month overloading revealed muscle fiber damage in DesKO, as indicated by the loss of sarcomere integrity and mitochondrial abnormalities. Moreover, the observed accumulation of autophagosomes and lysosomes in DesKO muscle fibers could indicate a blockage of autophagy. To address this issue, two main proteolysis pathways, the ubiquitin-proteasome system and autophagy, were explored in DesKO and control muscle. Our results suggested an alteration of proteolysis pathways in DesKO muscle in response to mechanical overloading.Conclusion: Taken together, our results show that mechanical overloading increases the negative impact of the lack of desmin on myofibril organization and mitochondria. Furthermore, our results suggest that under these conditions, the repairing activity of autophagy is disturbed. Consequently, force generation is not improved despite muscle growth, suggesting that desmin is required for a complete response to resistance training in skeletal muscle.

scholarly journals Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt

2009 ◽  
Vol 297 (5) ◽  
pp. 1124-1132 ◽  
Author(s):  
Michael R. Morissette ◽  
Stuart A. Cook ◽  
Cattleya Buranasombati ◽  
Michael A. Rosenberg ◽  
Anthony Rosenzweig
Keyword(s):  
Skeletal Muscle ◽  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Dominant Negative ◽  
Negative Regulator ◽  
C2c12 Myotubes ◽  
Akt Phosphorylation ◽  
Igf I

Myostatin is a highly conserved negative regulator of skeletal muscle growth. Loss of functional myostatin in cattle, mice, sheep, dogs, and humans results in increased muscle mass. The molecular mechanisms responsible for this increase in muscle growth are not fully understood. Previously, we have reported that phenylephrine-induced cardiac muscle growth and Akt activation are enhanced in myostatin knockout mice compared with controls. Here we report that skeletal muscle from myostatin knockout mice show increased Akt protein expression and overall activity at baseline secondary to an increase in Akt mRNA. We examined the functional role of myostatin modulation of Akt in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy. Adenoviral overexpression of myostatin attenuated the insulin-like growth factor-I (IGF-I)-mediated increase in myotube diameter, as well as IGF-I-stimulated Akt phosphorylation. Inhibition of myostatin by overexpression of the NH2-terminal portion of myostatin was sufficient to increase myotube diameter and Akt phosphorylation. Coexpression of myostatin and constitutively active Akt (myr-Akt) restored the increase in myotube diameter. Conversely, expression of dominant negative Akt (dn-Akt) with the inhibitory myostatin propeptide blocked the increase in myotube diameter. Of note, ribosomal protein S6 phosphorylation and atrogin-1/muscle atrophy F box mRNA were increased in skeletal muscle from myostain knockout mice. Together, these data suggest myostatin regulates muscle growth at least in part through regulation of Akt.

Resident stem cells are not required for exercise-induced fiber-type switching and angiogenesis but are necessary for activity-dependent muscle growth

2006 ◽  
Vol 290 (6) ◽  
pp. C1461-C1468 ◽  
Author(s):  
Ping Li ◽  
Takayuki Akimoto ◽  
Mei Zhang ◽  
R. Sanders Williams ◽  
Zhen Yan
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Intraperitoneal Injection ◽  
Fiber Type ◽  
Muscle Growth ◽  
Plantaris Muscle ◽  
Voluntary Running ◽  
Exercise Induced ◽  
Activity Dependent

Skeletal muscle undergoes active remodeling in response to endurance exercise training, and the underlying mechanisms of this remodeling remain to be defined fully. We have recently obtained evidence that voluntary running induces cell cycle gene expression and cell proliferation in mouse plantaris muscles that undergo fast-to-slow fiber-type switching and angiogenesis after long-term exercise. To ascertain the functional role of cell proliferation in skeletal muscle adaptation, we performed in vivo 5-bromo-2′-deoxyuridine (BrdU) pulse labeling (a single intraperitoneal injection), which demonstrated a phasic increase (5- to 10-fold) in BrdU-positive cells in plantaris muscle between days 3 and 14 during 4 wk of voluntary running. Daily intraperitoneal injection of BrdU for 4 wk labeled 2.0% and 15.4% of the nuclei in plantaris muscle in sedentary and trained mice, respectively, and revealed the myogenic and angiogenic fates of the majority of proliferative cells. Ablation of resident stem cell activity by X-ray irradiation did not prevent voluntary running-induced increases of type IIa myofibers and CD31-positive endothelial cells but completely blocked the increase in muscle mass. These findings suggest that resident stem cell proliferation is not required for exercise-induced type IIb-to-IIa fiber-type switching and angiogenesis but is required for activity-dependent muscle growth. The origin of the angiogenic cells in this physiological exercise model remains to be determined.

scholarly journals The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth

2004 ◽  
Vol 91 (3) ◽  
pp. 331-339 ◽  
Author(s):  
Stéphanie Bayol ◽  
Doiran Jones ◽  
Geoffrey Goldspink ◽  
Neil C. Stickland
Keyword(s):  
Skeletal Muscle ◽  
Growth Rate ◽  
Muscle Growth ◽  
Postnatal Growth ◽  
Nuclear Antigen ◽  
Control Group ◽  
Muscle Fibres ◽  
Control Muscle ◽  
Expression Of Genes ◽  
Ad Libitum

We examined the effects of two levels of gestational undernutrition (50% and 40% of ad libitum) on postnatal growth rate, skeletal muscle cellularity and the expression of genes that control muscle growth, in the offspring at weaning. The results showed that the rat pups born to mothers fed the 50% diet during gestation and a control diet during lactation had an increased postnatal growth rate compared with the pups fed the more restricted diet (40% of ad libitum). Surprisingly, the growth rate of the control group (ad libitum) was intermediate between the 50% and 40% groups. The restricted diets did not alter the number of muscle fibres in the semitendinosus muscle of the offspring but the number of muscle nuclei was reduced by 16% in the 40% group compared with the control group. In the 50% group, the lightest pups at birth (L) had elevated muscle insulin-like growth factor (IGF)-1, IGF binding protein (BP)-5 and proliferating cell nuclear antigen (PCNA) mRNA compared with the L pups from both the control and 40% groups. The heaviest pups at birth (H) in the 50% group had increased levels of IGFBP-4, PCNA and M-cadherin mRNA compared with both the control and 40% groups. Levels of IGF-1 receptor, myostatin and MyoD mRNA did not correlate with postnatal growth. Both H and L pups from the 40% group had reduced muscle IGF-1 mRNA but all other transcripts examined were similar to control levels. The results suggest that the increased postnatal growth rate, which accompanied milder fetal undernutrition (50%), may be due to a more active local muscle IGF system and increased muscle-cell proliferation.

scholarly journals Acute effects of insulin on skeletal muscle growth and differentiation genes in men with type 2 diabetes

2019 ◽  
Vol 181 (6) ◽  
pp. K55-K59 ◽  
Author(s):  
Sandeep Dhindsa ◽  
Husam Ghanim ◽  
Kelly Green ◽  
Sanaa Abuaysheh ◽  
Manav Batra ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Hypogonadotropic Hypogonadism ◽  
Muscle Growth ◽  
Quadriceps Muscle ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Potent Effect ◽  
Myogenic Regulatory Factor

Aims Insulin has anabolic effects on skeletal muscle. However, there is limited understanding of the molecular mechanisms underlying this effect in humans. We evaluated whether the skeletal muscle expression of satellite cell activator fibroblast growth factor 2 (FGF2) and muscle growth and differentiation factors are modulated acutely by insulin during euglycemic–hyperinsulinemic clamp (EHC). Design and methods This is a secondary investigation and analysis of samples obtained from a previously completed trial investigating the effect of testosterone replacement in males with hypogonadotropic hypogonadism and type 2 diabetes. Twenty men with type 2 diabetes underwent quadriceps muscle biopsies before and after 4 h of EHC. Results The infusion of insulin during EHC raised the expression of myogenic growth factors, myogenin (by 72 ± 20%) and myogenin differentiation protein (MyoD; by 81 ± 22%). Insulin reduced the expression of muscle hypertrophy suppressor, myogenic regulatory factor 4 (MRF4) by 34 ± 14%. In addition, there was an increase in expression of FGF receptor 2, but not FGF2, following EHC. The expression of myostatin did not change. Conclusions Insulin has an acute potent effect on expression of genes that can stimulate muscle differentiation and growth.

scholarly journals DLL4 and PDGF-BB regulate migration of human iPSC-derived skeletal myogenic progenitors

2021 ◽  
Author(s):  
Giulia Ferrari ◽  
SungWoo Choi ◽  
Louise Anne Moyle ◽  
Kirsty Mackinlay ◽  
Naira Naouar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Cell Migration ◽  
Negative Impact ◽  
Muscle Growth ◽  
Differentiation Potential ◽  
Cell Therapies ◽  
Muscle Gene

Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limited in vitro amplification and in vivo migration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscle groups such as muscular dystrophies. Several protocols have been established to derive progenitor cells similar to MuSCs from human induced pluripotent stem cells (hiPSCs), in order to establish a source of myogenic cells with controllable proliferation and differentiation capacity. However, currently available hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we provide evidence that activation of NOTCH and PDGF pathways with DLL4 and PDGF-BB improves migration of hiPSC-derived myogenic progenitors in vitro. Transcriptomic and functional analyses demonstrate that this property is conserved across species and multiple hiPSC lines, including genetically-corrected hiPSC derivatives from a patient with Duchenne muscular dystrophy. DLL4 and PDGF-BB treatment had no negative impact on cell proliferation; cells maintained their myogenic memory, with differentiation fully rescued by NOTCH inhibition. RNAseq analysis indicate that pathways involved in cell migration are modulated in treated myogenic progenitors, consistent with results from functional profiling of cell motility at single cell resolution. Notably, treated cells also showed enhanced trans-endothelial migration in transwell assays. Enhancing extravasation is a key translational milestone for intravascular delivery of hiPSC myogenic derivatives: our study establishes the foundations of a transgene-free, developmentally inspired strategy to achieve this goal, moving hiPSCs one step closer to future muscle gene and cell therapies.

PSV-13 Understanding the role of zinc and manganese in proliferation and protein synthesis of primary bovine satellite cells

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 308-308
Author(s):  
Anthony F Alberto ◽  
Laura A Smith ◽  
Caleb C Reichhardt ◽  
Stephanie L Hansen ◽  
Kara J Thornton
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
The Body ◽  
Trace Minerals ◽  
Trace Mineral ◽  
Bovine Skeletal Muscle ◽  
Free Media ◽  
And Control

Abstract Trace minerals are vital for the health and growth of livestock, supporting multiple biochemical processes in the body. There are several different signaling pathways that may be affected by trace minerals, ultimately altering growth of skeletal muscle. However, it is currently unknown how trace minerals specifically impact growth of skeletal muscle. As such, the objective of this study was to determine how zinc (Zn) and manganese (Mn) affect proliferation and protein synthesis of primary bovine satellite cell (BSC) cultures. Cultures were grown to 80% confluency and treated in 1% fetal bovine serum (control), 0.05, 0.10 or 0.25 µM of Mn, or 10, 20 or 40 µM of Zn to assess proliferation. Additionally, the above treatments were applied to fused BSC cultures in serum free media (control) to measure protein synthesis. The trace mineral concentrations chosen were based off known ranges of circulating concentrations of Zn or Mn. A series of contrasts were constructed to determine whether growth of BSC cultures was different between the treated and control cultures. Treatment with 10 µM Zn increased (P = 0.03) proliferation when compared to control cultures. However, treatment with Mn at the tested concentration did not (P > 0.12) result in proliferation rates that were different than the control cultures. Treatment with 10 µM Zn, 20 µM Zn, or 0.5 µM Mn increased (P < 0.05) protein synthesis compared to control cultures. These results indicate Zn is capable of increasing proliferation and both Zn and Mn increase protein synthesis of BSC cultures. Additional research is needed to couple trace mineral nutrition with knowledge of BSC biology to elucidate the molecular mechanisms by which trace minerals may function to support bovine skeletal muscle growth.

scholarly journals Chronic stress inhibits growth and induces proteolytic mechanisms through two different nonoverlapping pathways in the skeletal muscle of a teleost fish

2018 ◽  
Vol 314 (1) ◽  
pp. R102-R113 ◽  
Author(s):  
Cristián A. Valenzuela ◽  
Rodrigo Zuloaga ◽  
Luis Mercado ◽  
Ingibjörg Eir Einarsdottir ◽  
Björn Thrandur Björnsson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Chronic Stress ◽  
Stress Responses ◽  
Plasma Cortisol ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Igf System ◽  
Apoptosis Pathways ◽  
Ubiquitin Proteasome ◽  
Proteolytic Pathways

Chronic stress detrimentally affects animal health and homeostasis, with somatic growth, and thus skeletal muscle, being particularly affected. A detailed understanding of the underlying endocrine and molecular mechanisms of how chronic stress affects skeletal muscle growth remains lacking. To address this issue, the present study assessed primary (plasma cortisol), secondary (key components of the GH/IGF system, muscular proteolytic pathways, and apoptosis), and tertiary (growth performance) stress responses in fine flounder ( Paralichthys adspersus) exposed to crowding chronic stress. Levels of plasma cortisol, glucocorticoid receptor 2 ( gr2), and its target genes ( klf15 and redd1) mRNA increased significantly only at 4 wk of crowding ( P < 0.05). The components of the GH/IGF system, including ligands, receptors, and their signaling pathways, were significantly downregulated at 7 wk of crowding ( P < 0.05). Interestingly, chronic stress upregulated the ubiquitin-proteasome pathway and the intrinsic apoptosis pathways at 4wk ( P < 0.01), whereas autophagy was only significantly activated at 7 wk ( P < 0.05), and meanwhile the ubiquitin-proteasome and the apoptosis pathways returned to control levels. Overall growth was inhibited in fish in the 7-wk chronic stress trial ( P < 0.05). In conclusion, chronic stress directly affects muscle growth and downregulates the GH/IGF system, an action through which muscular catabolic mechanisms are promoted by two different and nonoverlapping proteolytic pathways. These findings provide new information on molecular mechanisms involved in the negative effects that chronic stress has on muscle anabolic/catabolic signaling balance.

scholarly journals Revisiting the roles of protein synthesis during skeletal muscle hypertrophy induced by exercise

2019 ◽  
Vol 317 (5) ◽  
pp. R709-R718 ◽  
Author(s):  
Vandré Casagrande Figueiredo
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Muscle Hypertrophy ◽  
Current Model ◽  
Muscle Growth ◽  
Exercise Session ◽  
Skeletal Muscle Hypertrophy ◽  
Resistance Exercise Session

Protein synthesis is deemed the underpinning mechanism enhancing protein balance required for skeletal muscle hypertrophy in response to resistance exercise. The current model of skeletal muscle hypertrophy induced by resistance training states that the acute increase in the rates of protein synthesis after each bout of resistance exercise is the basis for muscle growth. Within this paradigm, each resistance exercise session would add a specific amount of muscle mass; therefore, muscle hypertrophy could be defined as the result of intermittent and short-lived increases in muscle protein synthesis rates following each resistance exercise session. Although a substantial amount of data has accumulated in the last decades regarding the acute changes in protein synthesis (or translational efficiency) following resistance exercise, considerable gaps on the mechanism of muscle growth still exist. Ribosome biogenesis and translational capacity have emerged as important mediators of skeletal muscle hypertrophy. Recent advances in the field have demonstrated that skeletal muscle hypertrophy is associated with markers of translational capacity and long-term changes in protein synthesis under resting conditions. This review will discuss the caveats of the current model of skeletal muscle hypertrophy induced by resistance training while proposing a working model that takes into consideration the novel data generated by independent laboratories utilizing different methodologies. It is argued, herein, that the role of protein synthesis in the current model of muscle hypertrophy warrants revisiting.

scholarly journals Molecular Mechanisms of Skeletal Muscle Hypertrophy

2020 ◽  
pp. 1-15
Author(s):  
Stefano Schiaffino ◽  
Carlo Reggiani ◽  
Takayuki Akimoto ◽  
Bert Blaauw
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Hypertrophy ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Transcriptional Level ◽  
Ribosomal Biogenesis ◽  
Skeletal Muscle Hypertrophy ◽  
Positive Regulators ◽  
Exercise Muscle

Skeletal muscle hypertrophy can be induced by hormones and growth factors acting directly as positive regulators of muscle growth or indirectly by neutralizing negative regulators, and by mechanical signals mediating the effect of resistance exercise. Muscle growth during hypertrophy is controlled at the translational level, through the stimulation of protein synthesis, and at the transcriptional level, through the activation of ribosomal RNAs and muscle-specific genes. mTORC1 has a central role in the regulation of both protein synthesis and ribosomal biogenesis. Several transcription factors and co-activators, including MEF2, SRF, PGC-1α4, and YAP promote the growth of the myofibers. Satellite cell proliferation and fusion is involved in some but not all muscle hypertrophy models.

scholarly journals Genome-Wide Identification, Characterization and Expression Profiling of myosin Family Genes in Sebastes schlegelii

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 808
Author(s):  
Chaofan Jin ◽  
Mengya Wang ◽  
Weihao Song ◽  
Xiangfu Kong ◽  
Fengyan Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Muscle Growth ◽  
Myoblast Differentiation ◽  
Growth Stages ◽  
Marine Teleost ◽  
Black Rockfish ◽  
Skeletal Muscle Growth ◽  
Sebastes Schlegelii

Myosins are important eukaryotic motor proteins that bind actin and utilize the energy of ATP hydrolysis to perform a broad range of functions such as muscle contraction, cell migration, cytokinesis, and intracellular trafficking. However, the characterization and function of myosin is poorly studied in teleost fish. In this study, we identified 60 myosin family genes in a marine teleost, black rockfish (Sebastes schlegelii), and further characterized their expression patterns. myosin showed divergent expression patterns in adult tissues, indicating they are involved in different types and compositions of muscle fibers. Among 12 subfamilies, S. schlegelii myo2 subfamily was significantly expanded, which was driven by tandem duplication events. The up-regulation of five representative genes of myo2 in the skeletal muscle during fast-growth stages of juvenile and adult S. schlegelii revealed their active role in skeletal muscle fiber synthesis. Moreover, the expression regulation of myosin during the process of myoblast differentiation in vitro suggested that they contribute to skeletal muscle growth by involvement of both myoblast proliferation and differentiation. Taken together, our work characterized myosin genes systemically and demonstrated their diverse functions in a marine teleost species. This lays foundation for the further studies of muscle growth regulation and molecular mechanisms of indeterminate skeletal muscle growth of large teleost fishes.

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