scholarly journals Plantar mechanical stimulation attenuates protein synthesis decline in disused skeletal muscle via modulation of nitric oxide level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sergey A. Tyganov ◽  
Ekaterina Mochalova ◽  
Svetlana Belova ◽  
Kristina Sharlo ◽  
Sergey Rozhkov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathways ◽  
Soleus Muscle ◽  
Mechanical Stimulation ◽  
No Synthase ◽  
28S Rrna ◽  
Slow Type ◽  
Rat Soleus Muscle ◽  
Type Fiber

AbstractBoth research conducted under microgravity conditions and ground-based space analog studies have shown that air pump-based plantar mechanical stimulation (PMS) of cutaneous mechanoreceptors of the sole of the foot is able to increase neuromuscular activity in the musculature of the lower limbs. This type of stimulation is able to attenuate unloading-induced skeletal muscle atrophy and impaired muscle function. The aim of the present study was to evaluate the effects of PMS on anabolic signaling pathways in rat soleus muscle following 7-day hindlimb suspension (HS) and to elucidate if the effects of PMS on anabolic processes would be NO-dependent. The soles of the feet were stimulated with a frequency of 1-s inflation/1-s deflation with a total of 20 min followed by 10 min rest. This cycle was repeated for 4 h each day. We observed a decrease in the soleus muscle mass after 7-day HS, which was not prevented by PMS. We also observed a decrease in slow-type fiber cross-sectional area (CSA) by 56%, which significantly exceeded a decrease (–22%) in fast-type fiber CSA. PMS prevented a reduction in slow-twitch fiber CSA, but had no effect on fast-twitch fiber CSA. PMS prevented a 63% decrease in protein synthesis after 7-day HS as well as changes in several key anabolic signaling regulators, such as p70S6k, 4E-BP1, GSK3β, eEF-2, p90RSK. PMS also prevented a decrease in the markers of translational capacity (18S and 28S rRNA, c-myc, 45S pre-rRNA). Some effects of PMS on anabolic signaling were altered due to NO-synthase inhibitor (L-NAME) administration. Thus, PMS is able to partially prevent atrophic processes in rat soleus muscle during 7-day HS, affecting slow-type muscle fibers. This effect is mediated by alterations in anabolic signaling pathways and may depend on NO-synthase activity.

scholarly journals Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading

2016 ◽  
Vol 39 (3) ◽  
pp. 1011-1020 ◽  
Author(s):  
Timur Mirzoev ◽  
Sergey Tyganov ◽  
Natalia Vilchinskaya ◽  
Yulia Lomonosova ◽  
Boris Shenkman
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathways ◽  
Soleus Muscle ◽  
Ribosome Biogenesis ◽  
Hindlimb Unloading ◽  
Hindlimb Suspension ◽  
28S Rrna ◽  
Early Stages ◽  
Global Rate ◽  
Rat Soleus Muscle

Background/Aims: The purpose of the study was to assess the amount of rRNA and phosphorylation status of the key markers of mTORC1-dependent (70s6k, 4E-BP1) and mTORC1-independent (GSK-3β, AMPK) signaling pathways controlling protein synthesis in rat soleus during early stages of mechanical unloading (hindlimb suspension (HS) for 1-, 3- and 7 days). Methods: The content of the key signaling molecules of various anabolic signaling pathways was determined by Western-blotting. The amount of 28S rRNA was evaluated by RT-PCR. The rate of protein synthesis was assessed using in-vivo SUnSET technique. Results: HS for 3 and 7 days induced a significant (p<0.05) decrease in the rate of global protein synthesis in soleus muscle in comparison with control. HS within 24 hours resulted in a significant (p<0.05) decrease in p-4E-BP1 content, p-AMPK content and increase in p-p70s6k content in rat soleus muscle. Following three days of HS the content of p-AKT was decreased (p<0.05). After 7 days of HS the phosphorylation level of AKT and GSK-3beta was significantly reduced (p<0.05) compared to control. We also observed a significant decrease in the amount of 28S rRNA in rat soleus following 1, 3 and 7 days of HS. Conclusion: Taken together, the results of our study suggest that a decline in the global rate of protein synthesis in rat soleus during early stages of simulated microgravity is associated with impaired ribosome biogenesis as well as reduced activity of mTORC1-independent signaling pathways.

Signaling Pathways Regulating Protein Synthesis in the Rat Soleus Muscle in the Early Period of Gravitational Unloading

2017 ◽  
Vol 47 (3) ◽  
pp. 359-365
Author(s):  
T. M. Mirzoev ◽  
S. A. Tyganov ◽  
Yu. N. Lomonosova ◽  
P. E. Musienko ◽  
B. S. Shenkman
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathways ◽  
Soleus Muscle ◽  
Early Period ◽  
Gravitational Unloading ◽  
Rat Soleus Muscle

Mechanical signal transduction in skeletal muscle growth and adaptation

2005 ◽  
Vol 98 (5) ◽  
pp. 1900-1908 ◽  
Author(s):  
James G. Tidball
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Mechanical Activation ◽  
Signaling Pathways ◽  
Mechanical Stimulation ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Mechanical Signal ◽  
Igf I

The adaptability of skeletal muscle to changes in the mechanical environment has been well characterized at the tissue and system levels, but the mechanisms through which mechanical signals are transduced to chemical signals that influence muscle growth and metabolism remain largely unidentified. However, several findings have suggested that mechanical signal transduction in muscle may occur through signaling pathways that are shared with insulin-like growth factor (IGF)-I. The involvement of IGF-I-mediated signaling for mechanical signal transduction in muscle was originally suggested by the observations that muscle releases IGF-I on mechanical stimulation, that IGF-I is a potent agent for promoting muscle growth and affecting phenotype, and that IGF-I can function as an autocrine hormone in muscle. Accumulating evidence shows that at least two signaling pathways downstream of IGF-I binding can influence muscle growth and adaptation. Signaling via the calcineurin/nuclear factor of activated T-cell pathway has been shown to have a powerful influence on promoting the slow/type I phenotype in muscle but can also increase muscle mass. Neural stimulation of muscle can activate this pathway, although whether neural activation of the pathway can occur independent of mechanical activation or independent of IGF-I-mediated signaling remains to be explored. Signaling via the Akt/mammalian target of rapamycin pathway can also increase muscle growth, and recent findings show that activation of this pathway can occur as a response to mechanical stimulation applied directly to muscle cells, independent of signals derived from other cells. In addition, mechanical activation of mammalian target of rapamycin, Akt, and other downstream signals is apparently independent of autocrine factors, which suggests that activation of the mechanical pathway occurs independent of muscle-mediated IGF-I release.

Development of leptin resistance in rat soleus muscle in response to high-fat diets

2000 ◽  
Vol 279 (6) ◽  
pp. E1374-E1382 ◽  
Author(s):  
Greg R. Steinberg ◽  
David J. Dyck
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Soleus Muscle ◽  
Leptin Resistance ◽  
Safflower Oil ◽  
High Fat ◽  
Muscle Lipid ◽  
High Fat Diets ◽  
Rat Soleus Muscle ◽  
Fat Diets

Direct evidence for leptin resistance in peripheral tissues such as skeletal muscle does not exist. Therefore, we investigated the effects of different high-fat diets on lipid metabolism in isolated rat soleus muscle and specifically explored whether leptin's stimulatory effects on muscle lipid metabolism would be reduced after exposure to high-fat diets. Control (Cont, 12% kcal fat) and high-fat [60% kcal safflower oil (n-6) (HF-Saff); 48% kcal safflower oil plus 12% fish oil (n-3)] diets were fed to rats for 4 wk. After the dietary treatments, muscle lipid turnover and oxidation in the presence and absence of leptin was measured using pulse-chase procedures in incubated resting soleus muscle. In the absence of leptin, phospholipid, diacylglycerol, and triacylglycerol (TG) turnover were unaffected by the high-fat diets, but exogenous palmitate oxidation was significantly increased in the HF-Saff group. In Cont rats, leptin increased exogenous palmitate oxidation (21.4 ± 5.7 vs. 11.9 ± 1.61 nmol/g, P = 0.019) and TG breakdown (39.8 ± 5.6 vs. 27.0 ± 5.2 nmol/g, P = 0.043) and decreased TG esterification (132.5 ± 14.6 vs. 177.7 ± 29.6 nmol/g, P = 0.043). However, in both high-fat groups, the stimulatory effect of leptin on muscle lipid oxidation and hydrolysis was eliminated. Partial substitution of fish oil resulted only in the restoration of leptin's inhibition of TG esterification. Thus we hypothesize that, during the development of obesity, skeletal muscle becomes resistant to the effects of leptin, resulting in the accumulation of intramuscular TG. This may be an important initiating step in the development of insulin resistance common in obesity.

scholarly journals Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro

1998 ◽  
Vol 139 (1) ◽  
pp. 118-122 ◽  
Author(s):  
G Dimitriadis ◽  
B Leighton ◽  
M Parry-Billings ◽  
C Tountas ◽  
S Raptis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Transport Process ◽  
Glucose Utilization ◽  
Glucose Disposal ◽  
Rat Soleus Muscle ◽  
Lactate Formation

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.

Insulin increases a biochemically distinct pool of diacylglycerol in the rat soleus muscle

1994 ◽  
Vol 266 (3) ◽  
pp. E479-E485 ◽  
Author(s):  
K. S. Chen ◽  
S. J. Heydrick ◽  
M. L. Brown ◽  
J. C. Friel ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Molecular Species ◽  
Rat Skeletal Muscle ◽  
Glucose Carbon ◽  
Species Analysis ◽  
Rat Soleus Muscle ◽  
Molecular Species Analysis ◽  
Total Muscle ◽  
Do So

Insulin stimulates the incorporation of glucose-carbon into diacylglycerol (DAG) in rat skeletal muscle, and its ability to do so is enhanced severalfold after the muscle is denervated (S. J. Heydrick, N. B. Ruderman, T. J. Kurowski, H. A. Adams, and K. S. Chen. Diabetes 40: 1707-1711, 1991). The present studies were carried out to assess the nature of this newly synthesized DAG and to identify factors other than insulin that determine its rate of appearance in the incubated rat soleus muscle. In control muscles, incubated at a medium glucose concentration of 6-7.5 mM, insulin (10 mU/ml) increased DAG content (mass) by 20-25% and increased the incorporation of a 14C label from extracellular [14C]glucose into DAG by 200-300%. The labeling of DAG reached a plateau within 20 min, at which time the labeled DAG comprised a very small percentage of total muscle DAG. Molecular species analysis revealed that DAG species having fatty acids of 18:2/20:4 and 18:2/18:2 each constituted approximately 2% of total DAG content but contained 20 and 15%, respectively, of the glucose-derived label in DAG. In contrast, 16:0/18:1 accounted for > 80% of total DAG content but only 18% of the total label incorporated into DAG. Insulin did not alter this pattern. Denervation also did not alter the molecular species profiles of the labeled DAGs or DAG analyzed by mass. An increased incorporation of glucose-carbon into DAG was observed in muscles incubated with 30 mM glucose in place of the usual 7.5-mM concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

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