Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass

2007 ◽  
Vol 293 (1) ◽  
pp. C35-C44 ◽  
Author(s):  
F. Kawano ◽  
Y. Matsuoka ◽  
Y. Oke ◽  
Y. Higo ◽  
M. Terada ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Muscle Mass ◽  
Mechanical Load ◽  
Domain Size ◽  
Hindlimb Unloading ◽  
Cross Sectional ◽  
Ribosomal Protein S6 ◽  
Myonuclear Domain ◽  
Nucleolar Number ◽  
Integrated Electromyogram

Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1–2 to 3–5) within a myonucleus and myonuclear domain (+27%) compared with the preexperimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+84%) and HSP27 (+28%). Fiber atrophy (−52%), associated with decreased number (−31%) and domain size (−28%) of myonuclei and phosphorylation of S6 (−98%) and HSP27 (−63%), and with increased myonuclear size (+19%) and ubiquitination of myosin heavy chain (+33%, P > 0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (−47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+18%) by addition of synergist ablation, even though the integrated electromyogram level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

1998 ◽  
Vol 84 (4) ◽  
pp. 1407-1412 ◽  
Author(s):  
G. E. McCall ◽  
D. L. Allen ◽  
J. K. Linderman ◽  
R. E. Grindeland ◽  
R. R. Roy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Domain Size ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Igf I ◽  
Myonuclear Domain ◽  
The Difference ◽  
Saline Vehicle

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 ± 8 vs. 123 ± 16 mg. Muscle weight in the FO + GH/IGF-I group (196 ± 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 ± 445 μm2) was increased compared with the Con (2,044 ± 108 μm2) and FO (2,267 ± 301 μm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 ± 15 myonuclei/mm) and FO + GH/IGF-I (217 ± 23 myonuclei/mm) rats compared with Con (155 ± 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

scholarly journals Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoki Kuramoto ◽  
Kazuhiro Nomura ◽  
Daisuke Kohno ◽  
Tadahiro Kitamura ◽  
Gerard Karsenty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Hypertrophy ◽  
Mechanical Load ◽  
Static Condition ◽  
Ribosomal Protein S6 ◽  
Pi3k Signaling Pathway ◽  
Induced Changes

AbstractPhosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β2-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β2-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β2-AR.

Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers

1999 ◽  
Vol 87 (2) ◽  
pp. 634-642 ◽  
Author(s):  
Roland R. Roy ◽  
Steven R. Monke ◽  
David L. Allen ◽  
V. Reggie Edgerton
Keyword(s):  
Fiber Type ◽  
Domain Size ◽  
Cross Sectional Area ◽  
Type I ◽  
Fiber Types ◽  
Sectional Area ◽  
Tight Coupling ◽  
Fiber Volume ◽  
Cross Sectional ◽  
Myonuclear Domain

The effects of 10 wk of functional overload (FO), with and without daily treadmill endurance training, on the cross-sectional area, myonuclear number, and myonuclear domain size of mechanically isolated single fiber segments of the adult rat plantaris were determined. The fibers were typed on the basis of high-resolution gel electrophoresis for separation of specific myosin heavy chain (MHC) isoforms and grouped as type I+ (containing some type I MHC with or without any combination of fast MHCs), type IIa+ (containing some type IIa with or without some type IIx and/or IIb but no type I MHC), and type IIx/b (containing only type IIx and/or IIb MHCs). Type I+ fibers had a higher myonuclear number than did both fast types of fibers in the control and FO, but not in the FO and treadmill trained, rats. All fiber types in both FO groups had a significantly larger (36–90%) cross-sectional area and a significantly higher (61–109%) myonuclear number than did control. The average myonuclear domain size of each fiber type was similar among the three groups, except for a smaller domain size in the type IIx/b fibers of the FO compared with control. In general, these data indicate that during hypertrophy the number of myonuclei increase proportionally to the increase in fiber volume. The maintenance of myonuclear domain size near control values suggests that regulatory mechanisms exist that ensure a tight coupling between the quantity of genetic machinery and the protein requirements of a fiber.

scholarly journals Developmental effects on myonuclear domain size of rat diaphragm fibers

2008 ◽  
Vol 104 (3) ◽  
pp. 787-794 ◽  
Author(s):  
Carlos B. Mantilla ◽  
Rowan V. Sill ◽  
Bharathi Aravamudan ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck
Keyword(s):  
Postnatal Development ◽  
Domain Size ◽  
Diaphragm Muscle ◽  
Fiber Types ◽  
Rat Diaphragm ◽  
Cross Sectional ◽  
Early Postnatal Development ◽  
Fiber Growth ◽  
Myonuclear Domain ◽  
Isoform Expression

During early postnatal development in rat diaphragm muscle (Diam), significant fiber growth and transitions in myosin heavy chain (MHC) isoform expression occur. Similar to other skeletal muscles, Diam fibers are multinucleated, and each myonucleus regulates the gene products within a finite volume: the myonuclear domain (MND). We hypothesized that postnatal changes in fiber cross-sectional area (CSA) are associated with increased number of myonuclei so that the MND size is maintained. The Diam was removed at postnatal days 14 (P-14) and 28 (P-28). MHC isoform expression was determined by SDS-PAGE. Fiber CSA, myonuclear number, and MND size were measured using confocal microscopy. By P-14, significant coexpression of MHC isoforms was present with no fiber displaying singular expression of MHCNeo. By P-28, singular expression was predominant. MND size was not different across fiber types at P-14. Significant fiber growth was evident by P-28 at all fiber types (fiber CSA increased by 61, 93, and 147% at fibers expressing MHCSlow, MHC2A, and MHC2X, respectively). The number of myonuclei per unit of fiber length was similar across fibers at P-14, but it was greater at fibers expressing MHC2X at P-28. The total number of myonuclei per fiber also increased between P-14 and P-28 at all fiber types. Accordingly, MND size increased significantly by P-28 at all fiber types, and it became larger at fibers expressing MHC2X compared with fibers expressing MHCSlow or MHC2A. These results suggest that MND size is not maintained during the considerable fiber growth associated with postnatal development of the Diam.

scholarly journals Identifying the Structural Adaptations that Drive the Mechanical Load-Induced Growth of Skeletal Muscle: A Scoping Review

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1658 ◽  
Author(s):  
Kent W. Jorgenson ◽  
Stuart M. Phillips ◽  
Troy A. Hornberger
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Mechanical Loading ◽  
Skeletal Muscle Mass ◽  
Mechanical Load ◽  
Critical Role ◽  
Ultrastructural Changes ◽  
Clear Understanding ◽  
Cross Sectional

The maintenance of skeletal muscle mass plays a critical role in health and quality of life. One of the most potent regulators of skeletal muscle mass is mechanical loading, and numerous studies have led to a reasonably clear understanding of the macroscopic and microscopic changes that occur when the mechanical environment is altered. For instance, an increase in mechanical loading induces a growth response that is mediated, at least in part, by an increase in the cross-sectional area of the myofibers (i.e., myofiber hypertrophy). However, very little is known about the ultrastructural adaptations that drive this response. Even the most basic questions, such as whether mechanical load-induced myofiber hypertrophy is mediated by an increase in the size of the pre-existing myofibrils and/or an increase in the number myofibrils, have not been resolved. In this review, we thoroughly summarize what is currently known about the macroscopic, microscopic and ultrastructural changes that drive mechanical load-induced growth and highlight the critical gaps in knowledge that need to be filled.

The myonuclear domain is not maintained in skeletal muscle during either atrophy or programmed cell death

2016 ◽  
Vol 311 (4) ◽  
pp. C607-C615 ◽  
Author(s):  
Lawrence M. Schwartz ◽  
Christine Brown ◽  
Kevin McLaughlin ◽  
Wendy Smith ◽  
Carol Bigelow
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Dna Content ◽  
Sectional Area ◽  
Cross Sectional ◽  
Myonuclear Domain ◽  
Nuclear Number

Skeletal muscle mass can increase during hypertrophy or decline dramatically in response to normal or pathological signals that trigger atrophy. Many reports have documented that the number of nuclei within these cells is also plastic. It has been proposed that a yet-to-be-defined regulatory mechanism functions to maintain a relatively stable relationship between the cytoplasmic volume and nuclear number within the cell, a phenomenon known as the “myonuclear domain” hypothesis. While it is accepted that hypertrophy is typically associated with the addition of new nuclei to the muscle fiber from stem cells such as satellite cells, the loss of myonuclei during atrophy has been controversial. The intersegmental muscles from the tobacco hawkmoth Manduca sexta are composed of giant syncytial cells that undergo sequential developmental programs of atrophy and programmed cell death at the end of metamorphosis. Since the intersegmental muscles lack satellite cells or regenerative capacity, the tissue is not “contaminated” by these nonmuscle nuclei. Consequently, we monitored muscle mass, cross-sectional area, nuclear number, and cellular DNA content during atrophy and the early phases of cell death. Despite a ∼75–80% decline in muscle mass and cross-sectional area during the period under investigation, there were no reductions in nuclear number or DNA content, and the myonuclear domain was reduced by ∼85%. These data suggest that the myonuclear domain is not an intrinsic property of skeletal muscle and that nuclei persist through atrophy and programmed cell death.

Influence of brief daily tendon vibration on rat soleus muscle in non-weight-bearing situation

1999 ◽  
Vol 87 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Maurice Falempin ◽  
Soumeya Fodili In-Albon
Keyword(s):  
Relaxation Time ◽  
Muscle Mass ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Hindlimb Unloading ◽  
Tendon Vibration ◽  
Contraction Time ◽  
Constant Frequency ◽  
Cross Sectional

The purpose of this study was to investigate whether tendon vibration could prevent soleus muscle atrophy during hindlimb unloading (HU). Mechanical vibrations with a constant low amplitude (0.3 mm) were applied (192 s/day) with constant frequency (120 Hz) to the Achilles tendon of the unloaded muscle during the 14-day HU period. Significant reductions in muscle mass (−41%), fiber size, maximal twitch (−54%), and tetanic tensions (−73%) as well as changes in fiber type and electrophoretic profiles and twitch-time parameters (−31% in the contraction time and −30% in the half relaxation time) were found after 14 days of HU when compared with the control soleus. Tendon vibration applied during HU significantly attenuated, but did not prevent, 1) the loss of muscle mass (17 vs. 41%); 2) the decrease in the fiber cross-sectional area of type IIA (−28 vs. −50%) and type IIC (−29 vs. −56%) fibers; and 3) the decrease in maximal twitch (−3 vs. −54%) and maximal tetanic tensions (−29 vs. −73%) and the half relaxation time (1 vs. −30%). Changes in the contraction time and in histological and electrophoretical parameters associated with HU were not counteracted. These findings suggest that tendon vibration can be used as a paradigm to counteract the atrophic process observed after HU.

Influence of corticosteroids on myonuclear domain size in the rat diaphragm muscle

2004 ◽  
Vol 97 (5) ◽  
pp. 1715-1722 ◽  
Author(s):  
A. Jeroen Verheul ◽  
Carlos B. Mantilla ◽  
Wen-Zhi Zhan ◽  
Miguel Bernal ◽  
P. N. Richard Dekhuijzen ◽  
...  
Keyword(s):  
Muscle Growth ◽  
Domain Size ◽  
Male Rats ◽  
Diaphragm Muscle ◽  
Gene Products ◽  
Sectional Area ◽  
Rat Diaphragm ◽  
Normal Muscle ◽  
Cross Sectional ◽  
Myonuclear Domain

Skeletal muscle fibers are multinucleated. Each myonucleus regulates gene products and protein expression in only a restricted portion of the muscle fiber, the myonuclear domain (MND). In the rat diaphragm muscle (DIAm), corticosteroid (CoS) treatment causes atrophy of fibers containing myosin heavy chain (MHC): MHC2X and/or MHC2B. We hypothesized that DIAm fiber MND size is maintained during CoS-induced atrophy. Adult male rats received methylprednisolone for 11 days at 1 (CoS-Low, n = 8) or 8 mg·kg−1·day−1 (CoS-High, n = 8). Age-matched (CTL-AgeM, n = 8), sham-operated (SHAM-AgeM, n = 8), and weight-matched (CTL-WtM, n = 8) animals served as controls. In single DIAm fibers, cross-sectional area (CSA), MND size, and MHC expression were determined. Fiber CSA and MND size were similar in CTL-AgeM and SHAM-AgeM groups. Only fibers containing MHCslow or MHC2A displayed smaller CSA in CTL-WtM than in CTL-AgeM and SHAM-AgeM groups, and MND size was reduced in all fibers. Thus fibers containing MHCslow and MHC2A maintain the number of myonuclei, whereas MHC2X or MHC2B fibers show loss of myonuclei during normal muscle growth. Both CoS groups displayed smaller CSA and MND size than CTL-AgeM and SHAM-AgeM groups. However, compared with CTL-WtM DIAm fibers, only fibers containing MHC2X or MHC2B displayed reduced CSA and MND size after CoS treatment. Thus little, if any, loss of myonuclei was associated with CoS-induced atrophy of MHC2X or MHC2B DIAm fibers. In summary, MND size does not appear to be regulated during CoS-induced DIAm atrophy.

scholarly journals Prolonged Immobilization Exacerbates the Loss of Muscle Mass and Function Induced by Cancer-Associated Cachexia through Enhanced Proteolysis in Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 8167
Author(s):  
Laura Mañas-García ◽  
Antonio Penedo-Vázquez ◽  
Adrián López-Postigo ◽  
Jorieke Deschrevel ◽  
Xavier Durán ◽  
...  
Keyword(s):  
Muscle Damage ◽  
Muscle Mass ◽  
Muscle Regeneration ◽  
Troponin I ◽  
Hindlimb Unloading ◽  
Cross Sectional ◽  
Muscle Mass Loss ◽  
Prolonged Immobilization ◽  
And Function ◽  
Fast Twitch

We hypothesized that in mice with lung cancer (LC)-induced cachexia, periods of immobilization of the hindlimb (7 and 15 days) may further aggravate the process of muscle mass loss and function. Mice were divided into seven groups (n = 10/group): (1) non-immobilized control mice, (2) 7-day unloaded mice (7-day I), (3) 15-day unloaded mice (15-day I), (4) 21-day LC-cachexia group (LC 21-days), (5) 30-day LC-cachexia group (LC 30-days), (6) 21-day LC-cachexia group besides 7 days of unloading (LC 21-days + 7-day I), (7) 30-day LC-cachexia group besides 15 days of unloading (LC 30-days + 15-day I). Physiological parameters, body weight, muscle and tumor weights, phenotype and morphometry, muscle damage (including troponin I), proteolytic and autophagy markers, and muscle regeneration markers were identified in gastrocnemius muscle. In LC-induced cachexia mice exposed to hindlimb unloading, gastrocnemius weight, limb strength, fast-twitch myofiber cross-sectional area, and muscle regeneration markers significantly decreased, while tumor weight and area, muscle damage (troponin), and proteolytic and autophagy markers increased. In gastrocnemius of cancer-cachectic mice exposed to unloading, severe muscle atrophy and impaired function was observed along with increased muscle proteolysis and autophagy, muscle damage, and impaired muscle regeneration.

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