scholarly journals Decreased specific force and power production of muscle fibers from myostatin-deficient mice are associated with a suppression of protein degradation

2011 ◽  
Vol 111 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Christopher L. Mendias ◽  
Erdan Kayupov ◽  
Joshua R. Bradley ◽  
Susan V. Brooks ◽  
Dennis R. Claflin
Keyword(s):  
Myosin Heavy Chain ◽  
Muscle Mass ◽  
Heavy Chain ◽  
Extensor Digitorum Longus ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Force Production ◽  
Sectional Area ◽  
Cross Sectional ◽  
Maximum Isometric Force

Myostatin ( MSTN) is a member of the transforming growth factor-β superfamily of cytokines and is a negative regulator of skeletal muscle mass. Compared with MSTN+/+ mice, the extensor digitorum longus muscles of MSTN−/− mice exhibit hypertrophy, hyperplasia, and greater maximum isometric force production (Fo), but decreased specific maximum isometric force (sFo; Fo normalized by muscle cross-sectional area). The reason for the reduction in sFo was not known. Studies in myotubes indicate that inhibiting myostatin may increase muscle mass by decreasing the expression of the E3 ubiquitin ligase atrogin-1, which could impact the force-generating capacity and size of muscle fibers. To gain a greater understanding of the influence of myostatin on muscle contractility, we determined the impact of myostatin deficiency on the contractility of permeabilized muscle fibers and on the levels of atrogin-1 and ubiquitinated myosin heavy chain in whole muscle. We hypothesized that single fibers from MSTN−/− mice have a greater Fo, but no difference in sFo, and a decrease in atrogin-1 and ubiquitin-tagged myosin heavy chain levels. The results indicated that fibers from MSTN−/− mice have a greater cross-sectional area, but do not have a greater Fo and have a sFo that is significantly lower than fibers from MSTN+/+ mice. The extensor digitorum longus muscles from MSTN−/− mice also have reduced levels of atrogin-1 and ubiquitinated myosin heavy chain. These findings suggest that myostatin inhibition in otherwise healthy muscle increases the size of muscle fibers and decreases atrogin-1 levels, but does not increase the force production of individual muscle fibers.

Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight

1996 ◽  
Vol 81 (1) ◽  
pp. 145-151 ◽  
Author(s):  
D. L. Allen ◽  
W. Yasui ◽  
T. Tanaka ◽  
Y. Ohira ◽  
S. Nagaoka ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
Muscle Fibers ◽  
Cross Sectional Area ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Fiber Size

The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.

scholarly journals The Effects of Calcium-β-Hydroxy-β-Methylbutyrate on Aging-Associated Apoptotic Signaling and Muscle Mass and Function in Unloaded but Nonatrophied Extensor Digitorum Longus Muscles of Aged Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Brian T. Bennett ◽  
Junaith S. Mohamed ◽  
Stephen E. Alway
Keyword(s):  
Muscle Mass ◽  
Satellite Cells ◽  
Muscle Function ◽  
Extensor Digitorum Longus ◽  
Cross Sectional Area ◽  
Extensor Digitorum ◽  
Aged Rats ◽  
Sectional Area ◽  
Cross Sectional ◽  
Apoptotic Signaling

Beta-hydroxy-beta-methylbutyrate (HMB), a naturally occurring leucine metabolite, has been shown to attenuate plantar flexor muscle loss and increase myogenic stem cell activation during reloading after a period of significant muscle wasting by disuse in old rodents. However, it was less clear if HMB would alter dorsiflexor muscle response to unloading or reloading when there was no significant atrophy that was induced by unloading. In this study, we tested if calcium HMB (Ca-HMB) would improve muscle function and alter apoptotic signaling in the extensor digitorum longus (EDL) of aged animals that were unloaded but did not undergo atrophy. The EDL muscle was unloaded for 14 days by hindlimb suspension (HS) in aged (34-36 mo.) male Fisher 344×Brown Norway rats. The rats were removed from HS and allowed normal cage ambulation for 14 days of reloading (R). Throughout the study, the rats were gavaged daily with 170 mg of Ca-HMB or water 7 days prior to HS, then throughout 14 days of HS and 14 days of recovery after removing HS. The animals’ body weights were significantly reduced by ~18% after 14 days of HS and continued to decline by ~22% during R as compared to control conditions; however, despite unloading, EDL did not atrophy by HS, nor did it increase in mass after R. No changes were observed in EDL twitch contraction time, force production, fatigue resistance, fiber cross-sectional area, or markers of nuclear apoptosis (myonuclei + satellite cells) after HS or R. While HS and R increased the proapoptotic Bax protein abundance, BCL-2 abundance was also increased as was the frequency of TUNEL-positive myonuclei and satellite cells, yet muscle mass and fiber cross-sectional area did not change and Ca-HMB treatment had no effect reducing apoptotic signaling. These data indicate that (i) increased apoptotic signaling preceded muscle atrophy or occurred without significant EDL atrophy and (ii) that Ca-HMB treatment did not improve EDL signaling, muscle mass, or muscle function in aged rats, when HS and R did not impact mass or function.

scholarly journals Effects of inhaled fluticasone propionate on extrinsic tongue muscles in rats

2020 ◽  
Vol 128 (3) ◽  
pp. 576-585
Author(s):  
Christopher Setzke ◽  
Oleg Broytman ◽  
John A. Russell ◽  
Natalie Morel ◽  
Michelle Sonsalla ◽  
...  
Keyword(s):  
Fluticasone Propionate ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Inhaled Corticosteroids ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Tetanic Force ◽  
Obstructive Sleep ◽  
Tongue Muscles

Obstructive sleep apnea (OSA) is more common in patients with asthma, and inhaled corticosteroids may contribute to OSA pathogenesis in these patients. This study tested the effects of orally inhaled fluticasone propionate (FP) on extrinsic tongue muscles. Unanesthetized rats were treated with FP or placebo for 28 days. On day 29, tongue retrusive and protrusive functions were tested via hypoglossal nerve stimulation under a state of anesthesia, followed by genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscle extraction, after euthanasia, for histology [myosin heavy chain (MHC) fibers and laminin content reflecting extracellular matrix (ECM)]. On protrusive testing, FP increased percent maximum tetanic force at 40 Hz ( P = 0.03 vs. placebo) and endurance index ( P = 0.029 vs. placebo). On retrusive testing, FP increased maximum twitch ( P = 0.026 vs. placebo) and tetanic forces ( P = 0.02 vs. placebo) with no effect on endurance index. On histology, FP increased GG cross-sectional area of MHC type IIa ( P = 0.036 vs. placebo) and tended to increase type IIb ( P = 0.057 vs. placebo) fibers and HG MHC IIx fibers ( P = 0.065). The FP group had significantly increased laminin-stained areas, of greatest magnitude in the HG muscle. FP affects tongue protrusive and retrusive functions differently, concurrent with a shift in MHC fibers and increased ECM accumulation. These differential alterations may destabilize the tongue’s “muscle hydrostat” during sleep and promote collapse. NEW & NOTEWORTHY The effects of inhaled corticosteroid on upper airway may contribute to OSA pathogenesis in asthma. In this study, we tested the effects of orally inhaled fluticasone propionate on tongue protrusive and retrusive functions and on tongue extrinsic muscle fiber composition and molecular properties. We found that fluticasone treatment: 1) increased protrusive endurance and retrusive maximum twitch and tetanic force; and 2) on histology, increased cross-sectional area of myosin heavy chain (MHC) type IIa fibers and tended to increase cross-sectional area of MHC type IIb fibers in the protrusive muscle and of MHC IIx fibers in the retrusors. It also increased laminin-stained areas, across extrinsic tongue muscles, of greatest magnitude in the retrusors; and 3) reduced protein degradation and activated pathways associated with increased protein synthesis in the protrusor. These differential effects on the protrusors and retrusors may destabilize the tongue’s “muscle hydrostat” properties during sleep and promote collapse.

Mechanical deficit persists during long-term muscle hypertrophy

1990 ◽  
Vol 69 (3) ◽  
pp. 861-867 ◽  
Author(s):  
S. C. Kandarian ◽  
T. P. White
Keyword(s):  
Isometric Force ◽  
Force Production ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Plantaris Muscle ◽  
Cross Sectional ◽  
Control Value ◽  
Muscle Cross Sectional Area ◽  
Synergistic Muscle

Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production.

scholarly journals Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function

2015 ◽  
Vol 308 (11) ◽  
pp. C932-C943 ◽  
Author(s):  
Damien M. Callahan ◽  
Timothy W. Tourville ◽  
Mark S. Miller ◽  
Sarah B. Hackett ◽  
Himani Sharma ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Mitochondrial Content ◽  
Cross Sectional ◽  
Muscle Structure ◽  
Muscle Disuse

In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n = 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls ( n = 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in cross-sectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men. Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems.

Der Zusammenhang von dynamischen und isometrischen Maximalkraftparametern und Muskelquerschnitt bzw. Muskelvolumen

2014 ◽  
Vol 62 (1) ◽  
Keyword(s):  
Muscle Mass ◽  
Isometric Force ◽  
Body Height ◽  
Strength Test ◽  
Cross Sectional Area ◽  
Morphological Data ◽  
Morphological Parameters ◽  
Sectional Area ◽  
Maximal Strength ◽  
Cross Sectional

The aim of the study was the evaluation of the correlation between maximal strength and muscle mass depending on the kind of analysis which was used. Two different methods of strength evaluation and several morphological parameters were used. 77 male participants (age: 27,2 ± 6,6 years; body height: 179,9 ± 4,0 cm; body weight: 82,5 ± 10,4 kg) joined the study. Maximal strength was tested by measuring the isometric force (MIF) and analysing the one repetition maximum (1RM). The morphological data was captured by magnetic resonance imaging. The volume of the muscle (VOL), the biggest cross sectional area (QSMAX), the cross sectional area of the upper (QS30), middle (QS60) and lower (QS90) third of the scanned area of the arm flexors were examined. After analysing the data for normal distribution with the Kolmogorov-Smirnov-Test, the Pearson product moment correlation was used to quantify the correlation of the parameters. Significance level was set at 1%. The results of the study showed high correlations between the dynamic strength test and the morphological parameters (r = 0,77-0,82; p < 0,01) and moderate correlations between the isometric strength test and the morphological data (r = 0,46-0,53; p < 0,01). In addition, the two different parameters for maximal strength correlated moderately (r = 0,55; p < 0,01). The results of the study show that different morphological parameters can be used to describe the correlation between maximal strength and muscle mass. It should be recognised that the way of measuring maximal strength seems to be a substantial variable, which influences the apparent correlations.

Slow myosin heavy chain expression in the absence of muscle activity

2009 ◽  
Vol 296 (1) ◽  
pp. C205-C214 ◽  
Author(s):  
O. Agbulut ◽  
A. Vignaud ◽  
C. Hourde ◽  
E. Mouisel ◽  
F. Fougerousse ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Citrate Synthase ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Mouse Strains ◽  
Maximal Velocity ◽  
Slow Myosin ◽  
Relative Expression ◽  
Slow Myosin Heavy Chain

Innervation has been generally accepted to be a major factor involved in both triggering and maintaining the expression of slow myosin heavy chain (MHC-1) in skeletal muscle. However, previous findings from our laboratory have suggested that, in the mouse, this is not always the case ( 30 ). Based on these results, we hypothesized that neurotomy would not markedly reduced the expression of MHC-1 protein in the mouse soleus muscles. In addition, other cellular, biochemical, and functional parameters were also studied in these denervated soleus muscles to complete our study. Our results show that denervation reduced neither the relative amount of MHC-1 protein, nor the percentage of muscle fibers expressing MHC-1 protein ( P > 0.05). The fact that MHC-1 protein did not respond to muscle inactivity was confirmed in three different mouse strains (129/SV, C57BL/6, and CD1). In contrast, all of the other histological, biochemical, and functional muscle parameters were markedly altered by denervation. Cross-sectional area (CSA) of muscle fibers, maximal tetanic isometric force, maximal velocity of shortening, maximal power, and citrate synthase activity were all reduced in denervated muscles compared with innervated muscles ( P < 0.05). Contraction and one-half relaxation times of the twitch were also increased by denervation ( P < 0.05). Addition of tenotomy to denervation had no further effect on the relative expression of MHC-1 protein ( P > 0.05), despite a greater reduction in CSA and citrate synthase activity ( P < 0.05). In conclusion, a deficit in neural input leads to marked atrophy and reduction in performance in mouse soleus muscles. However, the maintenance of the relative expression of slow MHC protein is independent of neuromuscular activity in mice.

Advantage of normalizing force production to myofibrillar protein in skeletal muscle cross-sectional area

1994 ◽  
Vol 76 (2) ◽  
pp. 974-978 ◽  
Author(s):  
J. A. Taylor ◽  
S. C. Kandarian
Keyword(s):  
Soleus Muscle ◽  
Protein Concentration ◽  
Isometric Force ◽  
Force Production ◽  
Myofibrillar Protein ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Edl Muscle ◽  
Muscle Cross Sectional Area

When maximum isometric force (Po) is normalized to muscle cross-sectional area (CSA), intrinsic differences in force production among muscles may be masked by alterations in myofibrillar protein concentration or extracellular space. We tested the hypothesis that there is a greater deficit in Po when normalized to the average whole muscle CSA than when normalized to the myofibrillar protein CSA under conditions known to alter the concentration of myofibrils or connective tissue protein or interstitial fluid volume. Rats underwent either hindlimb unweighting (HU) to induce atrophy in the soleus muscle, sciatic nerve denervation to induce atrophy in the soleus and extensor digitorum longus (EDL) muscles, or ablation of gastrocnemius and plantaris muscles to induce hypertrophy in the soleus muscle. Po of the soleus muscle normalized to the muscle CSA (specific Po) was 58, 25, and 72% of control muscles with HU, denervation, and hypertrophy, respectively, whereas denervated EDL muscle specific Po was 60% of control muscles (P < 0.05). Soleus muscle Po normalized to the myofibrillar CSA was 80, 53, and 75% of control muscles with HU, denervation, and hypertrophy, respectively, whereas the denervated EDL muscle value was 82% of control muscles (P < 0.05). Both approaches to normalizing Po show force deficits, but normalization to the average myofibrillar protein in the muscle cross section gives values substantially closer to control values for HU and denervated muscles only. Data support the hypothesis because myofibrillar protein concentration is decreased in HU and denervation and interstitial space is increased in HU but neither parameter is altered with hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway smooth muscle contraction at birth: in vivo versus in vitro comparisons to the adult

1992 ◽  
Vol 70 (4) ◽  
pp. 590-596 ◽  
Author(s):  
John T. Fisher
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Airway Smooth Muscle ◽  
Heavy Chain ◽  
Force Generation ◽  
Sectional Area ◽  
Cross Sectional ◽  
Maximal Force

It is clear from the literature that considerable postnatal development occurs in the contractile properties of skeletal and cardiac muscle. Nevertheless, few studies have focused on developmental changes in airway smooth muscle or on the functional capabilities of airway innervation in the newborn. Conclusions about force generation, based on measurements of pulmonary mechanics during stimulation of the vagus nerves, suggest that the newborn possesses a reduced capability to narrow airway diameter relative to the adult. This reduced in vivo response is accompanied by a reduction in maximal force generating capabilities when compared on the basis of force per unit tissue cross-sectional area (stress) in vitro. However, studies of porcine airways suggest that such a finding may simply reflect a reduction in the relative amount of contractile protein (myosin heavy chain) as seen in fetal or preterm smooth muscle. Thus, comparisons based on force normalized per cross-sectional area of myosin alter conclusions from one in which fetal tracheal smooth muscle generates less maximal force than the adult, to one in which the fetal trachea has greater contractile capabilities. Interestingly, comparisons of maximal isometric force in bronchial smooth muscle between different age groups remain unaffected when myosin heavy chain normalization is applied. Finally, there appears to be an age at which maximal force is significantly greater than at any other age, independent of the amount of smooth muscle (determined morphologically), smooth muscle myosin content, or myosin isoform. Whether this enhanced in vitro response is reflected in vivo, or is counteracted by other physiological mechanisms, remains to be seen.Key words: development, airway smooth muscle, lung resistance, force generation, normalization, myosin.

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