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.

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.

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

scholarly journals HDAC4 Is Indispensable for Reduced Slow Myosin Expression at the Early Stage of Hindlimb Unloading in Rat Soleus Muscle

2021 ◽  
Vol 14 (11) ◽  
pp. 1167
Author(s):  
Inna I. Paramonova ◽  
Natalia A. Vilchinskaya ◽  
Boris S. Shenkman
Keyword(s):  
Mrna Expression ◽  
Soleus Muscle ◽  
Early Stage ◽  
Contractile Activity ◽  
Hindlimb Unloading ◽  
Hindlimb Suspension ◽  
Nuclear Accumulation ◽  
Myhc Isoforms ◽  
Rat Soleus Muscle ◽  
Slow Myhc

It is well known that reduced contractile activity of the main postural soleus muscle during long-term bedrest, immobilization, hindlimb unloading, and space flight leads to increased expression of fast isoforms and decreased expression of the slow isoform of myosin heavy chain (MyHC). The signaling cascade such as HDAC4/MEF2-D pathway is well-known to take part in regulating MyHC I gene expression. Earlier, we found a significant increase of HDAC4 in myonuclei due to AMPK dephosphorylation during 24 h of hindlimb unloading via hindlimb suspension (HU) and it had a significant impact on the expression of MyHC isoforms in rat soleus causing a decrease in MyHC I(β) pre-mRNA and mRNA expression as well as MyHC IIa mRNA expression. We hypothesized that dephosphorylated HDAC4 translocates into the nuclei and can lead to a reduced expression of slow MyHC. To test this hypothesis, Wistar rats were treated with HDAC4 inhibitor (Tasquinimod) for 7 days before HU as well as during 24 h of HU. We discovered that Tasquinimod treatment prevented a decrease in pre-mRNA expression of MyHC I. Furthermore, 24 h of hindlimb suspension resulted in HDAC4 nuclear accumulation of rat soleus but Tasquinimod pretreatment prevented this accumulation. The results of the study indicate that HDAC4 after 24 h of HU had a significant impact on the precursor MyHC I mRNA expression in rat soleus.

Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers

1996 ◽  
Vol 81 (6) ◽  
pp. 2540-2546 ◽  
Author(s):  
Robert J. Talmadge ◽  
Roland R. Roy ◽  
V. Reggie Edgerton
Keyword(s):  
Myosin Heavy Chain ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
De Novo ◽  
Weight Bearing ◽  
Muscle Fibers ◽  
Myosin Heavy Chain Isoforms ◽  
Hindlimb Suspension ◽  
Type I ◽  
Rat Soleus Muscle

Talmadge, Robert J., Roland R. Roy, and V. Reggie Edgerton.Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers. J. Appl. Physiol. 81(6): 2540–2546, 1996.—The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.

Lactate dehydrogenase expression at the onset of altered loading in rat soleus muscle

2004 ◽  
Vol 97 (4) ◽  
pp. 1424-1430 ◽  
Author(s):  
Tyrone A. Washington ◽  
James M. Reecy ◽  
Raymond W. Thompson ◽  
Larry L. Lowe ◽  
Joseph M. McClung ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Enzymatic Activity ◽  
Soleus Muscle ◽  
High Energy ◽  
Northern Blotting ◽  
Mrna Abundance ◽  
Hindlimb Suspension ◽  
Sprague Dawley ◽  
Muscle Lactate ◽  
Rat Soleus Muscle

Both functional overload and hindlimb disuse induce significant energy-dependent remodeling of skeletal muscle. Lactate dehydrogenase (LDH), an important enzyme involved in anaerobic glycolysis, catalyzes the interconversion of lactate and pyruvate critical for meeting rapid high-energy demands. The purpose of this study was to determine rat soleus LDH-A and -B isoform expression, mRNA abundance, and enzymatic activity at the onset of increased or decreased loading in the rat soleus muscle. The soleus muscles from male Sprague-Dawley rats were functionally overloaded for up to 3 days by a modified synergist ablation or subjected to disuse by hindlimb suspension for 3 days. LDH mRNA concentration was determined by Northern blotting, LDH protein isoenzyme composition was determined by zymogram analysis, and LDH enzymatic activity was determined spectrophotometrically. LDH-A mRNA abundance increased by 372%, and LDH-B mRNA abundance decreased by 43 and 31% after 24 h and 3 days of functional overload, respectively, compared with that in control rats. LDH protein expression demonstrated a shift by decreasing LDH-B isoforms and increasing LDH-A isoforms. LDH-B activity decreased 80% after 3 days of functional overload. Additionally, LDH-A activity increased by 234% following 3 days of hindlimb suspension. However, neither LDH-A or LDH-B mRNA abundance was affected following 3 days of hindlimb suspension. In summary, the onset of altered loading induced a differential expression of LDH-A and -B in the rat soleus muscle, favoring rapid energy production. Long-term altered loading is associated with myofiber conversion; however, the rapid changes in LDH at the onset of altered loading may be involved in other physiological processes.

scholarly journals Sex differences in forkhead box O3a signaling response to hindlimb unloading in rat soleus muscle

2018 ◽  
Vol 69 (2) ◽  
pp. 235-244 ◽  
Author(s):  
Toshinori Yoshihara ◽  
Toshiharu Natsume ◽  
Takamasa Tsuzuki ◽  
Shuo-wen Chang ◽  
Ryo Kakigi ◽  
...  
Keyword(s):  
Sex Differences ◽  
Soleus Muscle ◽  
Hindlimb Unloading ◽  
Forkhead Box ◽  
Rat Soleus Muscle ◽  
Forkhead Box O3a

Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading

1999 ◽  
Vol 87 (1) ◽  
pp. 386-390 ◽  
Author(s):  
Christopher P. Ingalls ◽  
Gordon L. Warren ◽  
R. B. Armstrong
Keyword(s):  
Soleus Muscle ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Hindlimb Unloading ◽  
Hindlimb Suspension ◽  
Confocal Laser ◽  
Specific Force ◽  
Activity Maximum ◽  
Tetanic Force ◽  
Intracellular Ca

The objective of this study was to determine whether altered intracellular Ca2+ handling contributes to the specific force loss in the soleus muscle after unloading and/or subsequent reloading of mouse hindlimbs. Three groups of female ICR mice were studied: 1) unloaded mice ( n = 11) that were hindlimb suspended for 14 days, 2) reloaded mice ( n = 10) that were returned to their cages for 1 day after 14 days of hindlimb suspension, and 3) control mice ( n = 10) that had normal cage activity. Maximum isometric tetanic force (Po) was determined in the soleus muscle from the left hindlimb, and resting free cytosolic Ca2+ concentration ([Ca2+]i), tetanic [Ca2+]i, and 4-chloro- m-cresol-induced [Ca2+]iwere measured in the contralateral soleus muscle by confocal laser scanning microscopy. Unloading and reloading increased resting [Ca2+]iabove control by 36% and 24%, respectively. Although unloading reduced Po and specific force by 58% and 24%, respectively, compared with control mice, there was no difference in tetanic [Ca2+]i. Po, specific force, and tetanic [Ca2+]iwere reduced by 58%, 23%, and 23%, respectively, in the reloaded animals compared with control mice; however, tetanic [Ca2+]iwas not different between unloaded and reloaded mice. These data indicate that although hindlimb suspension results in disturbed intracellular Ca2+ homeostasis, changes in tetanic [Ca2+]ido not contribute to force deficits. Compared with unloading, 24 h of physiological reloading in the mouse do not result in further changes in maximal strength or tetanic [Ca2+]i.

Myosin and troponin changes in rat soleus muscle after hindlimb suspension

1993 ◽  
Vol 74 (3) ◽  
pp. 1156-1160 ◽  
Author(s):  
M. Campione ◽  
S. Ausoni ◽  
C. Y. Guezennec ◽  
S. Schiaffino
Keyword(s):  
Soleus Muscle ◽  
Troponin I ◽  
Troponin T ◽  
High Mobility ◽  
Calcium Sensitivity ◽  
Hindlimb Suspension ◽  
Type I ◽  
Maximal Velocity ◽  
Rat Soleus Muscle ◽  
Fast Twitch

We examined the myosin heavy-chain (MHC), troponin T (TnT), and troponin I (TnI) isoform composition in the rat soleus muscle after 21 days of hindlimb suspension using electrophoretic and immunoblotting analysis with specific monoclonal antibodies. The suspended soleus showed a shift in the MHC isoform distribution with a marked increase (from 1.0 to 33%) in the relative amount of type IIa and IIx MHC and a corresponding decrease in type I MHC. However, type IIb MHC, which represents a major component in fast-twitch muscles, was not detected in suspended soleus muscles. TnT and TnI isoform composition was also changed with the appearance of fast-type TnI and TnT bands. However, a high-mobility TnT band, which represents a major component in fast-twitch muscles, was not expressed in suspended soleus. These isoform transitions may be related to the increased maximal velocity of shortening and higher calcium sensitivity previously reported in the rat soleus after hindlimb suspension.

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