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.

Stream habitat and rainbow trout (Oncorhynchus mykiss) physiological stress responses to streamside clear-cut logging in British Columbia

2005 ◽  
Vol 35 (3) ◽  
pp. 541-556 ◽  
Author(s):  
Eric Mellina ◽  
Scott G Hinch ◽  
Edward M Donaldson ◽  
Greg Pearson
Keyword(s):  
British Columbia ◽  
Rainbow Trout ◽  
Chronic Stress ◽  
Stress Responses ◽  
Plasma Cortisol ◽  
Acute Stress ◽  
Physiological Stress ◽  
Stream Habitat ◽  
Clear Cut ◽  
Rainbow Trout Oncorhynchus Mykiss

The impacts associated with streamside clear-cut logging (e.g., increased temperatures and sedimentation, loss of habitat complexity) are potentially stressful to stream-dwelling fish. We examined stream habitat and rainbow trout physiological stress responses to clear-cut logging in north-central British Columbia using 15 streams divided into three categories: old growth (reference), recently logged (clear-cut to both banks 1–9 years prior to the study), and second growth (clear-cut 25–28 years prior to the study). We used plasma cortisol and chloride concentrations as indicators of acute stress, and interrenal nuclear diameters, impairment of the plasma cortisol response, and trout condition and length-at-age estimates as indicators of chronic stress. No statistically significant acute or chronic stress responses to streamside logging were found, despite increases in summertime stream temperatures (daily maxima and diurnal fluctuations) and a reduction in the average overall availability of pool habitat. Our observed stress responses were approximately an order of magnitude lower than what has previously been reported in the literature for a variety of different stressors, and trout interrenal nuclear diameters responses to the onset of winter were approximately five times greater than those to logging. The overall consistency of our results suggests that the impacts of streamside clear-cut logging are not acutely or chronically stressful to rainbow trout in our study area.

scholarly journals Molecular Mechanisms, Therapeutic Targets and Pharmacological Interventions: An Update

2021 ◽  
Author(s):  
Mohit Kwatra ◽  
Sahabuddin Ahmed ◽  
Samir Ranjan Panda ◽  
Vegi Ganga Modi Naidu ◽  
Nitika Gupta
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Therapeutic Targets ◽  
The Body ◽  
Sirtuin 1 ◽  
Pharmacological Interventions ◽  
Ubiquitin Proteasome

Muscles are the enriched reservoir of proteins in the body. During any workout or exercise, the demand in the form of energy is essentially required by the muscle. Energy expenditure of skeletal muscle is more dependent on the type of demand. There is particular homeostasis within the body that avoid surplus energy expenditure and this prevents any muscle loss. Muscle atrophy is termed as the loss of skeletal muscle mass due to immobility, malnutrition, medications, aging, cancer cachexia, variety of injuries or diseases that impact the musculoskeletal or nervous system. Hence, atrophy within the skeletal muscle initiates further cause fatigue, pain, muscle weakness, and disability in human subjects. Therefore, starvation and reduced muscle mass further initiate numerous signaling pathways including inflammatory, antioxidant signaling, mitochondria bio-energetic failure, AMP-activated protein kinase (AMPK), Sirtuin 1(SIRT1), BDNF/TrkB/PKC, Autophagy, ubiquitin-proteasome systems, etc. Here, in this chapter, we will mention molecular mechanisms involved in therapeutic targets and available Pharmacological Interventions with the latest updates.

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.

scholarly journals The Molecular Mechanisms of Calpains Action on Skeletal Muscle Atrophy

2016 ◽  
pp. 547-560 ◽  
Author(s):  
J. HUANG ◽  
X. ZHU
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Therapeutic Interventions ◽  
Skeletal Muscle Atrophy ◽  
Akt Phosphorylation ◽  
Downstream Effects ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Skeletal muscle atrophy is associated with a loss of muscle protein which may result from both increased proteolysis and decreased protein synthesis. Investigations on cell signaling pathways that regulate muscle atrophy have promoted our understanding of this complicated process. Emerging evidence implicates that calpains play key roles in dysregulation of proteolysis seen in muscle atrophy. Moreover, studies have also shown that abnormally activated calpain results muscle atrophy via its downstream effects on ubiquitin-proteasome pathway (UPP) and Akt phosphorylation. This review will discuss the role of calpains in regulation of skeletal muscle atrophy mainly focusing on its collaboration with either UPP or Akt in atrophy conditions in hope to stimulate the interest in development of novel therapeutic interventions for skeletal muscle atrophy.

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.

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 &gt; 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 &lt; 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.

Abstract 3795: Readjusting The Catabolic-anabolic Balance In Heart Failure: Beneficial Effects Of Physical Exercise On Protein Catabolism In The Skeletal Muscle

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephan Gielen ◽  
Marcus Sandri ◽  
Volker Adams ◽  
Norman Mangner ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Vastus Lateralis ◽  
E3 Ligase ◽  
Tnf Alpha ◽  
Control Group ◽  
Vastus Lateralis Muscle ◽  
List Type ◽  
Ubiquitin Proteasome

Background: Progressive muscle wasting frequently occurs in the course of chronic heart failure (CHF) and has recently been identified as independent predictor of mortality in clincal studies. However, the molecular mechanisms that mediate muscle catabolism are still largely unknown and no specific pharmacological agents are available to antagonize the loss of muscle mass. We therefore tested the potential of an established anabolic intervention, i.e. exercise training, to prevent cytokine-induced ubiquitin-proteasome-mediated protein degradation in the skeletal muscle of stable patients with advanced CHF. Methods: 43 CHF-patients and 41 healthy subjects (HS) were prospectively randomized to 4 weeks of supervised bicycle ergometer training at 70% of the heart rate reserve 4 times 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, and skeletal muscle biopsy from the vastus lateralis muscle were performed. Expression of TNF-alpha and the E3 ligase Murf-1, which tags proteins for degradation via the ubiquitin-proteasome system, were quantified by real-time PCR standardized for 18S-rRNA. Results: In CHF patients (age 60.3 ± 2.9 years, BMI 28.9 ± 1.7, LV-EF 27.4 ± 1.7%): training increased VO2max from 14.9 ± 3.3 to 18.1 ± 4.7 mL/min/kg (p<0.01 vs. C), and LV-EF from 26.8 ± 4.6 to 33.1 ± 5.5% (p=0.001 vs. C). At baseline Murf-1 expression was significantly higher as compared to HS. Training decreased Murf-1 expression from 0.49 ± 0.21 to 0.22 ± 0.07 rel. units (p<0.05) and TNF-alpha expression from 79 ± 7.1 to 44.7 ± 5.9 rel. units (p<0.001). In HS (age 64.7 ± 2.7 years, BMI 26.2 ± 0.5, LV-EF 63 ± 0.8%) training increased VO2 max from 20.3 ± 2.1 to 27.9.2 ± 1.3 mL/kg min (p=0.01 vs. C). Murf-1 and TNF-alpha expression remained unchanged versus untrained HS. Conclusions: CHF is associated with local inflammatory and catabolic activation in the skeletal muscle as indicated by higher baseline TNF-alpha and Murf-1 levels. Training cuts the elevated TNF-alpha and E3-ligase expressions by half within only four weeks of intervention. These findings emphasize the role of training for the prevention of muscle atrophy and may provide a novel explanation for the prognostic benefits of exercise in CHF.

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.

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

2012 ◽  
Vol 302 (5) ◽  
pp. R643-R654 ◽  
Author(s):  
Thomas Chaillou ◽  
Nathalie Koulmann ◽  
Nadine Simler ◽  
Adélie Meunier ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Female Rats ◽  
Mrna Levels ◽  
Hypertrophic Response ◽  
Protein Levels ◽  
Skeletal Muscle Hypertrophy

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70S6K and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70S6K pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

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