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.

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 PO-121 Influence of HDAC1 inhibitor on the E3-ligases expression in rat soleus during hindlimb unloading

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Svetlana Belova ◽  
Ekaterina Mochalova ◽  
Boris Shenkman ◽  
Tatiana Nemirovskaya
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Early Stage ◽  
Hindlimb Unloading ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
Russian Science ◽  
E3 Ligases ◽  
Histone Deacetylase 1 ◽  
Muscle Unloading

Objective Muscle unloading leads to its atrophy development. The MuRF-1 and MAFbx E3-ligases expression is increasing under this condition. FOXO3 was considered to be the only transcription factor that triggers E3-ligases expression. Beharry A.W. et al pinpoints HDAC1 as a primary regulator of FoxO in skeletal muscle that is both sufficient and required for skeletal muscle atrophy. We aimed to determine the role of histone deacetylase 1 (HDAC1) proteins in activation of MuRF-1 and MAFbx E3-ligases expression at the early stage of muscle unloading. Methods We investigate it by CI-994 (inhibitor of HDAC1) administration in male Wistar rats (180-200 g) upon 3-day hindlimb suspension. The method of hindlimb suspension was described in Morey-Holton E & Globus R (2002). 24 animals were divided into 3 groups (n=8 in each): C-control, CI - hindlimb suspension with CI-994 (i.p. 1 mg/kg/day), or placebo (HS group) administration. The animals were anaesthetized with an i.p. injection of tribromoethanol (240 mg/kg), soleus muscles were surgically excised, frozen in liquid nitrogen. The Western blot and RT-PCR analyzes were done. The statistical analysis was performed using REST 2009 v.2.0.12 and Bio-Rad CFX Manager programs at the significance level set at 0.05. The significant differences between groups were statistically analyzed using Mann-Whitney test. Results The evaluation of the levels of mRNA expression of MuRF-1 and MAFbx showed that CI-994 treatment inhibited unloading induced up-regulation of MAFbx in CI group but had no effect on mRNA expression of MuRF-1. After unloading, mRNA expression of MAFbx increased 2.12-fold (p < 0.05) in HS group. There were statistically significant differences in MAFbx mRNA expression between HS and CI groups. When compared with the control, unloading increased MuRF-1 mRNA expression  1.67- and 1.56-fold in HS and CI groups, respectively. CI-994 treatment also inhibited unloading-induced upregulation of mRNA expression of ubiquitin. The levels of ubiquitin mRNA expression when compared with the control were 4.21- and 2.32-fold in HS and CI groups, respectively. We did not find any differences in the content of phosphorylated anabolic signaling system components (Akt/mTOR/S6k) between both suspended groups (CI and HS). Conclusions Therefore, HDAC1 inhibiting prevented hindlimb suspension-induced up-regulation of MAFbx and ubiquitin, but did not any effect MuRF-1expression. This work was supported by Russian Science Foundation (grant № 18-15-00062).

scholarly journals Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ekaterina P. Mochalova ◽  
Svetlana P. Belova ◽  
Timur M. Mirzoev ◽  
Boris S. Shenkman ◽  
Tatiana L. Nemirovskaya
Keyword(s):  
Mrna Expression ◽  
Histone Deacetylase ◽  
Soleus Muscle ◽  
Hindlimb Unloading ◽  
Histone Deacetylase 1 ◽  
Rat Soleus Muscle

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.

Excitation-induced activation of the Na(+)-K+ pump in rat skeletal muscle

1994 ◽  
Vol 266 (4) ◽  
pp. C925-C934 ◽  
Author(s):  
M. E. Everts ◽  
T. Clausen
Keyword(s):  
Soleus Muscle ◽  
Contractile Activity ◽  
Activation Mechanism ◽  
Rat Skeletal Muscle ◽  
Ouabain Binding ◽  
Direct Stimulation ◽  
Rat Soleus Muscle ◽  
Fold Stimulation ◽  
86Rb Influx ◽  
Stimulation Of

The stimulating effect of excitation on the Na(+)-K+ pump was characterized in measurements of 22Na efflux, intracellular Na+ content, 86Rb influx, and [3H]ouabain binding in isolated rat soleus muscle. Direct stimulation (10 V, 1 ms, 2 Hz) rapidly increased 22Na efflux and 86Rb influx about twofold. These effects were blocked by tetracaine and ouabain, were not associated with any significant increase in intracellular Na+, and could not be attributed to a rise in extracellular K+. The stimulation of 22Na efflux was unaffected by tubocurarine, dantrolene, trifluoperazine, or bumetanide. Stimulation at 2 Hz increased the rate of [3H]ouabain binding by approximately 120% within 1 min, indicating an early specific activation of the Na(+)-K+ pump. Stimulation at 60 Hz for 10 s increased intracellular Na+ content by 58%. Reextrusion of Na+ was complete in 2 min and could be prevented by ouabain (10(-4) M) or by cooling to 0 degrees C. It is concluded that, in rat soleus muscle, excitation leads to a rapid and pronounced (up to 15-fold) stimulation of the Na(+)-K+ pump, even at modest increases in intracellular Na+. This activation mechanism may be essential for the maintenance of transmembrane Na(+)-K+ gradients and prompt recovery of excitability during contractile activity.

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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