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 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.

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.

Running during recovery from hindlimb suspension induces transient muscle injury

1990 ◽  
Vol 68 (2) ◽  
pp. 533-539 ◽  
Author(s):  
C. E. Kasper ◽  
T. P. White ◽  
L. C. Maxwell
Keyword(s):  
Soleus Muscle ◽  
Recovery Period ◽  
Morphological Characteristics ◽  
Cross Sectional Area ◽  
Hindlimb Suspension ◽  
Type I ◽  
Sectional Area ◽  
Cross Sectional ◽  
Female Wistar Rats ◽  
Type I Fibers

The objectives were to study morphological adaptations of soleus muscle to decreased loading induced by hindlimb suspension and the effect of run training during the subsequent recovery period. Adult female Wistar rats were kept for 28 days with hindlimbs suspended. For the next 28 days, rats were assigned to a cage-sedentary or daily running group. Compared with control soleus muscles, 28 days of hindlimb suspension reduced the mass and fiber cross-sectional area to 58 and 53% of control values, respectively, and decreased type I fibers from 92 +/- 2 to 81 +/- 2%. During recovery, clusters of damaged fibers were observed in the soleus muscle, and this observation was more pronounced in trained animals. Type IIc fibers appeared transiently during recovery, and their presence was exacerbated with training, as IIc fibers increased to approximately 20% of the total by day 14 of recovery and were no longer evident at day 28. Although muscle wet mass does not differ as a result of mode of recovery at day 14, training transiently decreased the overall fiber area compared with sedentary recovery at this point. By day 28 of recovery the morphological characteristics of soleus muscle in the trained group did not differ from control muscle, whereas in the sedentary group muscle mass and overall fiber cross-sectional area were approximately 14% less than control values.

Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension

1994 ◽  
Vol 77 (1) ◽  
pp. 290-297 ◽  
Author(s):  
B. A. St Pierre ◽  
J. G. Tidball
Keyword(s):  
Soleus Muscle ◽  
Weight Bearing ◽  
Recovery Process ◽  
Wistar Rat ◽  
Hindlimb Suspension ◽  
Muscle Necrosis ◽  
Macrophage Subpopulations ◽  
Rat Soleus Muscle ◽  
Developmental Myosin Heavy Chain ◽  
Immunohistochemical Techniques

The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells was similar to that of control. Ia+ macrophages decreased to 240/mm2 at 4 days but after 7 days rose above control values to 429/mm2. ED2+ macrophages in 4- and 7-day reloaded soleus increased 70–80% in the interstitial spaces compared with control but were not observed to infiltrate necrotic muscle fibers at any time points. Immunohistochemistry and immunoblots using a monoclonal anti-dMHC antibody demonstrate a greater proportion of myofibers expressing dMHC isoforms after 4 and 7 days of reloading. These findings indicate that macrophage subpopulations are associated with distinct stages during the recovery process from hindlimb suspension: ED1+ macrophages are associated with muscle necrosis, whereas ED2+ cells are associated with muscle regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Whole body and muscle respiratory capacity with dobutamine and hindlimb suspension

1991 ◽  
Vol 71 (6) ◽  
pp. 2419-2424 ◽  
Author(s):  
D. Desplanches ◽  
R. Favier ◽  
B. Sempore ◽  
H. Hoppeler
Keyword(s):  
Soleus Muscle ◽  
Metabolic Response ◽  
Volume Density ◽  
Hindlimb Suspension ◽  
Whole Body ◽  
Capillary Length ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Beneficial Effects ◽  
Mitochondrial Volume

The effects of repeated injections of dobutamine, a synthetic catecholamine, were studied in control and tail-suspended rats to determine whether this drug could improve the metabolic response to unweighting. Dobutamine prevented the decrease in maximal oxygen uptake (VO2max) induced by hindlimb suspension. Furthermore, VO2max was 12% greater in dobutamine-treated animals than in saline-treated control animals. Soleus muscle weight and mean fiber cross-sectional area were decreased by 60 and 75%, respectively, in saline- and dobutamine-treated suspended rats. Total capillary length was unaffected by unweighting and increased 21% in all animals receiving dobutamine. The drug prevented the increase in total mitochondrial volume density (+30%) induced by unweighting but did not change total mitochondrial volume. Our results suggest that 1) dobutamine is useful to prevent the decrease of total aerobic capacity during hindlimb suspension, 2) dobutamine increases VO2max in control rats, and 3) total capillary length in soleus muscle is increased by the drug in all groups, although no beneficial effects on mitochondria can be detected.

Rat soleus muscle ultrastructure after hindlimb suspension

1990 ◽  
Vol 69 (2) ◽  
pp. 504-508 ◽  
Author(s):  
D. Desplanches ◽  
S. R. Kayar ◽  
B. Sempore ◽  
R. Flandrois ◽  
H. Hoppeler
Keyword(s):  
Soleus Muscle ◽  
Capillary Density ◽  
Volume Density ◽  
Hindlimb Suspension ◽  
Tail Suspension ◽  
Cross Sectional ◽  
Muscle Ultrastructure ◽  
Rat Soleus Muscle ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density

The aim of the present investigation was to determine, by quantitative electron microscopy, the effects of a 5-wk tail-suspension period on rat soleus muscle ultrastructure. A marked decline (-60%) in muscle mass occurred. The mean fiber cross-sectional area decreased to a greater extent (-75%) than the capillary-to-fiber ratio (-37%), leading to a higher capillary density (+148%) after hypokinesia. The total mitochondrial volume density remained unchanged, whereas the volume density of myofibrils was slightly but significantly reduced (-6%). A shift from subsarcolemmal to interfibrillar mitochondria occurred. Interfibrillar mitochondrial volume density was highest near the fiber border and decreased toward the fiber center. An increase in volume density of satellite cells suggested muscle regenerative events. Soleus atrophy with tail suspension greatly decreases the muscular volume but leaves the ultrastructural composition of muscle fibers relatively unaffected.

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