scholarly journals Evidences of apoptosis during the early phases of soleus muscle atrophy in hindlimb suspended mice

2008 ◽  
pp. 601-611
Author(s):  
R Ferreira ◽  
MJ Neuparth ◽  
R Vitorino ◽  
HJ Appell ◽  
F Amado ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Protein Concentration ◽  
Time Course ◽  
Hindlimb Suspension ◽  
Phagocytic Cells ◽  
P53 Expression ◽  
Wet Weight ◽  
Apoptosis Inducing Factor ◽  
Early Phases

The purpose of this study was to investigate the occurrence and time-course of apoptosis in soleus skeletal muscle during the first 48 hours of unloading. Fifty Charles River mice were randomly divided into five groups (n=10 each) according to the time of hindlimb suspension (HS). Mice were suspended for 0 (Control), 6 (6HS), 12 (12HS), 24 (24HS), and 48 hours (48HS). Soleus muscle atrophy was confirmed by a significant decrease of 20 % in muscle-wet weight and of 5 % in the ratio protein concentration/muscle wet-weight observed after 48 hours of unloading. The apoptotic index, the AIF (apoptosis-inducing factor) and p53 expression presented their uppermost value (304 %, 241 % and 246 %, respectively) at 24HS, and were preceded by the highest activity of caspase-3 and -8 at 12HS (170 % and 218 %, respectively) and of Bax/Bcl-2 content at 6HS (160 %). There were no marked ultrastructural alterations until 24 hours of simulated weightlessness. Lysosomal autophagic activity and infiltration of phagocytic cells were observed at 24HS and 48HS and might have contributed to the degenerative changes noticed in both groups. Though not consistently supported by morphological evidences, the biochemical parameters sustain the concept that the occurrence of apoptosis parallels the soleus atrophic response in its early phase.

scholarly journals Modulation of Muscle Atrophy, Fatigue and MLC Phosphorylation by MuRF1 as Indicated by Hindlimb Suspension Studies on MuRF1-KO Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Siegfried Labeit ◽  
Christine H. Kohl ◽  
Christian C. Witt ◽  
Dittmar Labeit ◽  
Jeong Jung ◽  
...  
Keyword(s):  
Muscle Fatigue ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Coiled Coil ◽  
Hindlimb Suspension ◽  
Twitch Potentiation ◽  
Muscle Tissues ◽  
Mlc Phosphorylation ◽  
First Time ◽  
Muscle Unloading

MuRF1 is a member of the TRIM/RBCC superfamily, a gene family that encompasses a large variety of proteins, all sharing the conserved TRIM (TripartiteMotive) sequential array ofRING,B-box, and coiled-coil domains. Within this family, MuRF1(also named TRIM63) is a specialized member that contributes to the development of muscle atrophy and sarcopenia. Here we studied MuRF1's role in muscle atrophy during muscle unloading induced by hindlimb suspension. Consistent with previous studies, we found that MuRF1 inactivation leads to an attenuated muscle atrophy response. The amount of protection was higher as compared to the denervation model, and within the 10 day-suspension period the soleus muscle was spared from atrophy in MuRF1-KO mice. Contractility studies on hindlimb suspended muscle tissues suggested that MuRF1's functions extend beyond muscle trophicity and implicate MuRF1 in muscle fatigue and MLC phosphorylation control: soleus muscle from MuRF1-KO mice fatigued significantly faster and in addition showed a reduced posttetanic twitch potentiation. Thus the present work further established the role of MuRF1 in muscle atrophy and for the first time shows that MuRF1 plays a role in muscle fatigue and twitch potentiation.

An E-box within the MHC IIB gene is bound by MyoD and is required for gene expression in fast muscle

1999 ◽  
Vol 276 (5) ◽  
pp. C1069-C1078 ◽  
Author(s):  
Matthew T. Wheeler ◽  
Emily C. Snyder ◽  
Melissa N. Patterson ◽  
Steven J. Swoap
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Soleus Muscle ◽  
Time Course ◽  
De Novo ◽  
Hindlimb Suspension ◽  
Causative Role ◽  
Dependent Manner ◽  
E Box ◽  
Mhc Iib

The myosin heavy chain (MHC) IIB gene is selectively expressed in skeletal muscles, imparting fast contractile kinetics. Why the MHC IIB gene product is expressed in muscles like the tibialis anterior (TA) and not expressed in muscles like the soleus is currently unclear. It is shown here that the mutation of an E-box within the MHC IIB promoter decreased reporter gene activity in the fast-twitch TA muscle 90-fold as compared with the wild-type promoter. Reporter gene expression within the TA required this E-box for activation of a heterologous construct containing upstream regulatory regions of the MHC IIB promoter linked to the basal 70-kDa heat shock protein TATA promoter. Electrophoretic mobility shift assays demonstrated that mutation of the E-box prevented the binding of both MyoD and myogenin to this element. In cotransfected C2C12myotubes and Hep G2 cells, MyoD preferentially activated the MHC IIB promoter in an E-box-dependent manner, whereas myogenin activated the MHC IIB promoter to a lesser extent, and in an E-box-independent manner. A time course analysis of hindlimb suspension demonstrated that the unweighted soleus muscle activated expression of MyoD mRNA before the de novo expression of MHC IIB mRNA. These data suggest a possible causative role for MyoD in the observed upregulation of MHC IIB in the unweighted soleus muscle.

Effects of torbafylline on muscle atrophy: prevention and recovery

1992 ◽  
Vol 70 (6) ◽  
pp. 814-820 ◽  
Author(s):  
Souad Aboudrar ◽  
Dominique Desplanches ◽  
Fränzi Graber-von Bergen ◽  
Roland Favier ◽  
Ismahan Okyayuz-Baklouti ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Extensor Digitorum Longus ◽  
Recovery Period ◽  
Recovery Process ◽  
Hindlimb Suspension ◽  
Structural And Functional Properties ◽  
Mitochondrial Volume ◽  
Ultrastructural Characteristics ◽  
Baseline Values

The effects of torbafylline on the prevention of and the recovery from 5 weeks of hindlimb suspension induced atrophy were analyzed in rat soleus and extensor digitorum longus muscles. Muscle alterations were investigated by determining a suite of electrophysiological, histochemical, and muscle ultrastructural characteristics. Administration of torbafylline during the suspension period was ineffective in preventing any of the observed muscle atrophic changes. Application of torbafylline during the recovery period resulted in a faster recovery of some soleus muscle structural and functional properties. Mitochondrial volume densities and capillary to fiber ratios returned towards baseline values earlier in the recovery process with torbafylline. Furthermore, the drug significantly improved soleus muscle fatigue resistance 4 weeks after cessation of hindlimb suspension.Key words: xanthine, rat muscle contraction, histocytochemistry, mitochondria, capillaries.

scholarly journals Evidence of MyomiR network regulation of β-myosin heavy chain gene expression during skeletal muscle atrophy

2009 ◽  
Vol 39 (3) ◽  
pp. 219-226 ◽  
Author(s):  
John J. McCarthy ◽  
Karyn A. Esser ◽  
Charlotte A. Peterson ◽  
Esther E. Dupont-Versteegden
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
Hindlimb Suspension ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene

There is a growing recognition that noncoding RNAs (ncRNA) play an important role in the regulation of gene expression. A class of small (19–22 nt) ncRNAs, known as microRNAs (miRs), have received a great deal of attention lately because of their ability to repress gene expression through a unique posttranscriptional 3′-untranslated region (UTR) mechanism. The objectives of the current study were to identify miRs expressed in the rat soleus muscle and determine if their expression was changed in response to hindlimb suspension. Comprehensive profiling revealed 151 miRs were expressed in the soleus muscle and expression of 18 miRs were significantly ( P < 0.01) changed after 2 and/or 7 days of hindlimb suspension. The significant decrease (16%) in expression of muscle-specific miR-499 in response to hindlimb suspension was confirmed by RT-PCR and suggested activation of the recently proposed miR encoded by myosin gene (MyomiR) network during atrophy. Further analysis of soleus muscle subjected to hindlimb suspension for 28 days provided evidence consistent with MyomiR network repression of β-myosin heavy chain gene (β-MHC) expression. The significant downregulation of network components miR-499 and miR-208b by 40 and 60%, respectively, was associated with increased expression of Sox6 (2.2-fold) and Purβ (23%), predicted target genes of miR-499 and known repressors of β-MHC expression. A Sox6 3′-UTR reporter gene confirmed Sox6 is a target gene of miR-499. These results further expand the role of miRs in adult skeletal muscle and are consistent with a model in which the MyomiR network regulates slow myosin expression during muscle atrophy.

scholarly journals Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Violetta V. Kravtsova ◽  
Vladimir V. Matchkov ◽  
Elena V. Bouzinova ◽  
Alexander N. Vasiliev ◽  
Irina A. Razgovorova ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Hindlimb Suspension ◽  
Resting Membrane Potential ◽  
Membrane Localization ◽  
Specific Effects ◽  
Contractile Parameters ◽  
Mrna Content ◽  
Rat Soleus Muscle

This study examines the isoform-specific effects of short-term hindlimb suspension (HS) on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24–72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP) of muscle fibers; the electrogenic activity, protein, and mRNA content of theα1 andα2 Na,K-ATPase; the functional activity and plasma membrane localization of theα2 Na,K-ATPase. Our results indicate that 24–72 h of HS specifically decreases the electrogenic activity of the Na,K-ATPaseα2 isozyme and the RMP of soleus muscle fibers. This decrease occurs prior to muscle atrophy or any change in contractile parameters. Theα2 mRNA and protein content increased after 24 h of HS and returned to initial levels at 72 h; however, even the increased content was not able to restoreα2 enzyme activity in the disused soleus muscle. There was no change in the membrane localization ofα2 Na,K-ATPase. Theα1 Na,K-ATPase electrogenic activity, protein and mRNA content did not change. Our findings suggest that skeletal muscle use is absolutely required forα2 Na,K-ATPase transport activity and provide the first evidence that Na,K-ATPase alterations precede HS-induced muscle atrophy.

scholarly journals Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

Nutrients ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 1100 ◽  
Author(s):  
Gabriel Nasri Marzuca-Nassr ◽  
Gilson Masahiro Murata ◽  
Amanda Roque Martins ◽  
Kaio Fernando Vitzel ◽  
Amanda Rabello Crisma ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Hindlimb Suspension ◽  
Balanced Diet

Elevated interstitial fluid volume in soleus muscles unweighted by spaceflight or suspension

1993 ◽  
Vol 75 (4) ◽  
pp. 1650-1653 ◽  
Author(s):  
E. J. Henriksen ◽  
M. E. Tischler ◽  
C. R. Woodman ◽  
K. A. Munoz ◽  
C. S. Stump ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Interstitial Fluid ◽  
Fluid Volume ◽  
Female Rats ◽  
Hindlimb Suspension ◽  
Microgravity Environment ◽  
Muscle Weight ◽  
Interstitial Fluid Volume ◽  
Significant Difference ◽  
Wet Weight

Recent evidence by Kandarian et al. (J. Appl. Physiol. 71: 910#x2013;914, 1991) indicates that prolonged (28 days) unweighting of the rat soleus by hindlimb suspension results in a substantial increase in interstitial fluid volume (IFV), as defined by the inulin space. The lack of any significant difference in absolute IFV values between unweighted and control groups suggested that this elevated IFV was a consequence of muscle atrophy. Using young female rats, we directly tested this hypothesis by comparing the early responses of soleus muscle weight and IFV with unweighting by tail-cast suspension or actual exposure to microgravity during spaceflight. Significant differences from control were first observed after 3 days of suspension unweighting for soleus wet weight (-14%; P < 0.01) and IFV (+35%; P < 0.01) and increased further after 6 days (-32% and +53%, respectively; both P < 0.001). After 5.4 days of spaceflight, soleus wet weight was 38% less and IFV was 52% greater than control (both P < 0.001). A highly significant negative correlation between soleus wet weight and IFV for all groups was observed (r = -0.70, P < 0.001). These data indicate that elevated soleus IFV develops at an early time point during unweighting and that there is a direct relationship between the magnitude of this increase in IFV and the extent of muscle atrophy. This relationship also exists in soleus muscles unweighted by exposure to a microgravity environment.

Glycogen supercompensation in rat soleus muscle during recovery from nonweight bearing

1989 ◽  
Vol 66 (6) ◽  
pp. 2782-2787 ◽  
Author(s):  
E. J. Henriksen ◽  
C. R. Kirby ◽  
M. E. Tischler
Keyword(s):  
Soleus Muscle ◽  
Enzyme Activities ◽  
Glycogen Phosphorylase ◽  
Time Course ◽  
Glycogen Synthase ◽  
Hindlimb Suspension ◽  
Phosphorylase Activity ◽  
Rat Soleus Muscle ◽  
Made In

The time course of glycogen changes in soleus muscle recovering from 3 days of nonweight bearing by hindlimb suspension was investigated. Within 15 min and up to 2 h, muscle glycogen decreased. Coincidentally, muscle glucose 6-phosphate and the fractional activity of glycogen phosphorylase, measured at the fresh muscle concentrations of AMP, increased. Increased fractional activity of glycogen synthase during this time was likely the result of greater glucose 6-phosphate and decreased glycogen. From 2 to 4 h, when the synthase activity remained elevated and the phosphorylase activity declined, glycogen levels increased (glycogen supercompensation). A further increase of glycogen up to 24 h did not correlate with the enzyme activities. Between 24 and 72 h, glycogen decreased to control values, possibly initiated by high phosphorylase activity at 24 h. At 12 and 24 h, the inverse relationship between glycogen concentration and the synthase activity ratio was lost, indicating that reloading transiently uncoupled glycogen control of this enzyme. These data suggest that the activities of glycogen synthase and phosphorylase, when measured at physiological effector levels, likely provide the closest approximation to the actual enzyme activities in vivo. Measurements made in this way effectively explained the majority of the changes in the soleus glycogen content during recovery from nonweight bearing.

Temporal alterations in protein signaling cascades during recovery from muscle atrophy

2003 ◽  
Vol 285 (2) ◽  
pp. C391-C398 ◽  
Author(s):  
Thomas E. Childs ◽  
Espen E. Spangenburg ◽  
Dharmesh R. Vyas ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Time Course ◽  
Glycogen Synthase ◽  
Early Time ◽  
Protein Translation ◽  
Skeletal Muscle Atrophy ◽  
Time Points

Currently, the repertoire of cellular and molecular pathways that control skeletal muscle atrophy and hypertrophy are not well defined. It is possible that intracellular regulatory signaling pathways are active at different times during the muscle hypertrophy process. The hypothesis of the given experiments was that cellular signals related to protein translation would be active at early time points of skeletal muscle regrowth, whereas transcriptional signals would be active at later time points of skeletal muscle regrowth. The phosphorylation status of p38 MAPK and JNK increased at the end of limb immobilization but returned to control values at recovery day 3. Transient increases in phosphorylation and in protein concentration occurred during recovery of soleus muscle mass. Phosphorylation of Akt, p70S6k, and signal transducer and activator of transcription 3 (STAT3) peaked on recovery day 3 compared with day 0. Glycogen synthase kinase (GSK)-3β phosphorylation was increased on the sixth and fifteenth recovery day. In addition, transient peaks in seven protein concentrations occurred at different times of recovery: STAT3, calcineurin A (CaNA), CaNB, and β4E-BP1 protein concentrations peaked on the third recovery day; p70S6k, STAT3, Akt, and GSK3-β peaked on the sixth recovery day; and GSK3-β peaked on the fifteenth recovery day. The apexes of STAT3 and GSK3-β protein concentrations remained elevated for two recovery time points. Thus the time course of increase in molecules of signaling pathways differed as the young rat soleus muscle regrew from an atrophied state.

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