Influence of overload on phenotypic remodeling in regenerated skeletal muscle

2001 ◽  
Vol 281 (5) ◽  
pp. C1686-C1694 ◽  
Author(s):  
A. X. Bigard ◽  
J. Zoll ◽  
F. Ribera ◽  
P. Mateo ◽  
H. Sanchez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Lactate Dehydrogenase ◽  
Sarcoplasmic Reticulum ◽  
Heavy Chain ◽  
Type I ◽  
Similar Extent ◽  
Surgical Ablation ◽  
Control Of Gene Expression ◽  
Mechanical Overload

We studied the effects of 10 wk of functional overload on the expression of myosin heavy chain (MHC), sarcoplasmic reticulum Ca2+-ATPase isoforms (SERCA), and the activity of several metabolic enzymes in sham and regenerated plantaris muscles. Overload was accomplished by bilateral surgical ablation of its synergists 4 wk after right plantaris muscles regenerated after myotoxic infiltration. The overload-induced muscle enlargement was slightly less in regenerated than in sham muscles [28% ( P < 0.005) and 43% ( P < 0.001), respectively]. Overload led to an increase in type I MHC expression ( P < 0.01) to a similar extent in sham and regenerated plantaris, while the expected shift from type IIb to type IIa MHC was less marked in regenerated than in sham plantaris. The overload-induced decrease in the expression of the fast SERCA isoform and in the activity of the M subunit of lactate dehydrogenase occurred to a similar extent in sham and regenerated plantaris [66% ( P < 0.01) and 27% ( P < 0.005), respectively]. In conclusion, the lesser responses of muscle mass and fast MHC composition of regenerated plantaris to mechanical overload suggest an alteration of the transcriptional, translational, and/or posttranslational control of gene expression in regenerated muscle.

scholarly journals Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle

2009 ◽  
Vol 297 (4) ◽  
pp. R1037-R1048 ◽  
Author(s):  
Clay E. Pandorf ◽  
Weihua H. Jiang ◽  
Anqi X. Qin ◽  
Paul W. Bodell ◽  
Kenneth M. Baldwin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Fiber Type ◽  
Hindlimb Suspension ◽  
Chain Gene ◽  
Type I ◽  
Thyroid State

The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T3)] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T3 was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg·kg−1·day−1) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T3 ( P < 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression.

Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

2001 ◽  
Vol 90 (1) ◽  
pp. 345-357 ◽  
Author(s):  
Kenneth M. Baldwin ◽  
Fadia Haddad
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Motor Proteins ◽  
Weight Bearing ◽  
Activity Level ◽  
Type I ◽  
Mechanical Stimuli ◽  
Energy Deprivation

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T3, 3,5,3′-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T3/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the β-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T3 or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T3 and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.

scholarly journals Sp3 Proteins Negatively Regulate β Myosin Heavy Chain Gene Expression during Skeletal Muscle Inactivity

2004 ◽  
Vol 24 (24) ◽  
pp. 10777-10791 ◽  
Author(s):  
Gretchen Tsika ◽  
Juan Ji ◽  
Richard Tsika
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Weight Bearing ◽  
C2c12 Myotubes ◽  
Type I ◽  
Adult Skeletal Muscle ◽  
Nuclear Extracts ◽  
Muscle Inactivity

ABSTRACT In adult skeletal muscle, β myosin heavy chain (βMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression is down-regulated in response to muscle inactivity. Little is known about the signaling pathways and transcription factors that mediate this important functional response. This study demonstrates that increased binding of Sp3 to GC-rich elements in theβ MyHC promoter is a critical event in down-regulation ofβ MyHC gene expression under non-weight-bearing conditions. Conversely, binding of Sp3 to these elements decreased while Sp1 binding increased with nuclear extracts from plantaris muscle exposed to mechanical overload, a stimulus that increases βMyHC gene expression. In addition, these experiments revealed the existence of an Sp4-DNA binding complex when using adult skeletal muscle nuclear extract was used but not when nuclear extracts from cultured myotubes were used. Sp3 proteins are competitive inhibitors of Sp1-mediatedβ MyHC reporter gene transactivation in both Drosophila SL-2 and mouse C2C12 myotubes. Sp4 is a weak activator of βMyHC gene expression in SL-2 cells, which lack endogenous Sp1 activity, but does not activate βMyHC gene expression in C2C12 myotubes, which have high levels of Sp1. These results suggest that competitive binding of Sp family proteins regulate βMyHC gene transcription in response to altered neuromuscular activity.

scholarly journals Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthieu Dos Santos ◽  
Stéphanie Backer ◽  
Benjamin Saintpierre ◽  
Brigitte Izac ◽  
Muriel Andrieu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Neuromuscular Junction ◽  
Heavy Chain ◽  
Transcriptional Activity ◽  
Rna Seq ◽  
Hybrid Fibers ◽  
Adult Mice ◽  
Single Nucleus

Abstract Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. Here we show by snRNA-seq and snATAC-seq that slow, fast, myotendinous and neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states and combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one of the three fast isoforms of Myosin heavy chain (MYH) proteins, while a small number of hybrid fibers can express more than one MYH. By snRNA-seq and FISH, we show that the majority of myonuclei within a myofiber are synchronized, coordinately expressing only one fast Myh isoform with a preferential panel of muscle-specific genes. Importantly, this coordination of expression occurs early during post-natal development and depends on innervation. These findings highlight a previously undefined mechanism of coordination of gene expression in a syncytium.

scholarly journals Regulation of endocrine and paracrine sources of Igfs and Gh receptor during compensatory growth in hybrid striped bass (Morone chrysops×Morone saxatilis)

2008 ◽  
Vol 199 (1) ◽  
pp. 81-94 ◽  
Author(s):  
Matthew E Picha ◽  
Marc J Turano ◽  
Christian K Tipsmark ◽  
Russell J Borski
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Striped Bass ◽  
Compensatory Growth ◽  
Morone Saxatilis ◽  
Type I ◽  
Hybrid Striped Bass ◽  
Morone Chrysops ◽  
Gh Receptor ◽  
Catabolic State

Compensatory growth (CG) is a period of growth acceleration that exceeds normal rates after animals are alleviated of certain growth-stunting conditions. In hybrid striped bass (HSB, Morone chrysops×Morone saxatilis), 3 weeks of complete feed restriction results in a catabolic state that, when relieved, renders a subsequent phase of CG. The catabolic state was characterized by depressed levels of hepatic Type I and II GH receptor (ghr1, ghr2) and igf1 mRNA, along with considerable decreases in plasma Igf1. The state of catabolism also resulted in significant declines in hepatic igf2 mRNA and in circulating 40 kDa Igf-binding protein (Igfbp). Skeletal muscle expression of ghr2 mRNA was significantly increased. Upon realimentation, specific growth rates (SGRs) were significantly higher than sized-matched controls, indicating a period of CG. Hepatic ghr1, ghr2, igf1 and igf2 mRNA levels along with plasma Igf1 and 40 kDa Igfbp increased rapidly during realimentation. Plasma Igf1 and total hepatic igf2 mRNA were significantly correlated to SGR throughout the study. Skeletal muscle igf1 mRNA also increased tenfold during CG. These data suggest that endocrine and paracrine/autocrine components of the GH–Igf axis, namely igf1, igf2, and ghr1 and ghr2, may be involved in CG responses in HSB, with several of the gene expression variables exceeding normal levels during CG. We also demonstrate that normalization of hepatic mRNA as a function of total liver production, rather than as a fraction of total RNA, may be a more biologically appropriate method of quantifying hepatic gene expression when using real-time PCR.

scholarly journals Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle

2018 ◽  
Vol 125 (5) ◽  
pp. 1536-1554 ◽  
Author(s):  
Mette Flindt Heisterberg ◽  
Jesper L. Andersen ◽  
Peter Schjerling ◽  
Alberte Lund ◽  
Simone Dalskov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Angiotensin Ii ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Satellite Cells ◽  
Type I ◽  
Elderly Men ◽  
Fiber Area ◽  
Heavy Resistance Exercise

Our purpose here was to investigate the potential of blocking the angiotensin II type I receptor (AT1R) on the hypertrophy response of elderly human skeletal muscle to 4 mo of heavy-resistance exercise training. Fifty-eight healthy elderly men (+65 yr) were randomized into three groups, consuming either AT1R blocker (losartan, 100 mg/day) or placebo for 4 mo. Two groups performed resistance training (RT) and were treated with either losartan or placebo, and one group did not train but was treated with losartan. Quadriceps muscle biopsies, MR scans, and strength tests were performed at baseline and after 8 and 16 wk. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells, capillaries, fiber type distribution, and fiber area. Gene expression levels of myostatin, connective tissue, and myogenic signaling pathways were determined by real-time RT-PCR. Four months of heavy-resistance training led in both training groups to expected improvements in quadriceps (∼3–4%) and vastus lateralis (∼5–6%), cross-sectional area, and type II fiber area (∼10–18%), as well as dynamic (∼13%) and isometric (∼19%) quadriceps peak force, but with absolutely no effect of losartan on these outcomes. Furthermore, no changes were seen in satellite cell number with training, and most gene targets failed to show any changes induced by training or losartan treatment. We conclude that there does not appear to be any effect of AT1R blocking in elderly men during 4 mo of resistance training. Therefore, we do not find any support for using AT1R blockers for promoting muscle adaptation to training in humans. NEW & NOTEWORTHY Animal studies have suggested that blocking angiotensin II type I receptor (AT1R) enhances muscle regeneration and prevents disuse atrophy, but studies in humans are limited. Focusing on hypertrophy, satellite cells, and gene expression, we found that AT1R blocking did not result in any greater responses with 4 mo of resistance training. These results do not support previous findings and question the value of blocking AT1R in the context of preserving aging human muscle.

Skeletal Muscle Sarcoplasmic Reticulum Ca 2+ -ATPase Gene Expression in Congestive Heart Failure

1997 ◽  
Vol 81 (5) ◽  
pp. 703-710 ◽  
Author(s):  
David G. Peters ◽  
Heather L. Mitchell ◽  
Sylvia A. McCune ◽  
Sonhee Park ◽  
Jay H. Williams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Congestive Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Atpase Gene

MHC and sarcoplasmic reticulum protein isoforms in functionally overloaded cat plantaris muscle fibers

1996 ◽  
Vol 80 (4) ◽  
pp. 1296-1303 ◽  
Author(s):  
R. J. Talmadge ◽  
R. R. Roy ◽  
G. R. Chalmers ◽  
V. R. Edgerton
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Heavy Chain ◽  
Muscle Fibers ◽  
Protein Isoforms ◽  
Type I ◽  
Single Muscle ◽  
Plantaris Muscle ◽  
Plasmic Reticulum ◽  
Deep Region ◽  
Isoform Expression

To determine whether the adaptations in myosin heavy chain (MHC) isoform expression after functional overload (FO) are accompanied by commensurate adaptations in protein isoforms responsible for relaxation [sarco(endo)plasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (SERCA) and phospholamban (PHL)] in single muscle fibers, the isoforms of MHC and SERCA and the presence or absence of PHL were determined for cat plantaris fibers 3 mo after FO. In control plantaris the relative MHC isoform composition was 23% type I, 21% type IIa, and 56% type IIb. FO resulted in a shift toward slower isoforms (33% type I, 44% type IIa, and 23% type IIb). In the deep region of the plantaris the proportions of type I MHC and hybrid MHC fibers (containing type I and II MHCs) were 40 and 200% greater in FO cats, respectively. FO resulted in a 47% increase in the proportion of fibers containing only the slow SERCA isoform (SERCA2) and a 41% increase in the proportion of fibers containing PHL. The proportions of fibers containing type I MHC, SERCA2, and PHL in control and FO plantaris were linearly correlated. These data show that adaptations in MHC isoform expression are accompanied by commensurate adaptations in sarcoplasmic reticulum protein isoforms in single muscle fibers after FO.

scholarly journals Properties of skeletal muscle in the teleost Sternopygus macrurus are unaffected by short-term electrical inactivity

2016 ◽  
Vol 48 (9) ◽  
pp. 699-710 ◽  
Author(s):  
Robert Güth ◽  
Alexander Chaidez ◽  
Manoj P. Samanta ◽  
Graciela A. Unguez
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Electrical Activity ◽  
Muscle Fiber ◽  
Model Systems ◽  
Control Fish ◽  
Type I ◽  
Fiber Types ◽  
Spinal Transection ◽  
Fiber Size

Skeletal muscle is distinguished from other tissues on the basis of its shape, biochemistry, and physiological function. Based on mammalian studies, fiber size, fiber types, and gene expression profiles are regulated, in part, by the electrical activity exerted by the nervous system. To address whether similar adaptations to changes in electrical activity in skeletal muscle occur in teleosts, we studied these phenotypic properties of ventral muscle in the electric fish Sternopygus macrurus following 2 and 5 days of electrical inactivation by spinal transection. Our data show that morphological and biochemical properties of skeletal muscle remained largely unchanged after these treatments. Specifically, the distribution of type I and type II muscle fibers and the cross-sectional areas of these fiber types observed in control fish remained unaltered after each spinal transection survival period. This response to electrical inactivation was generally reflected at the transcript level in real-time PCR and RNA-seq data by showing little effect on the transcript levels of genes associated with muscle fiber type differentiation and plasticity, the sarcomere complex, and pathways implicated in the regulation of muscle fiber size. Data from this first study characterizing the acute influence of neural activity on muscle mass and sarcomere gene expression in a teleost are discussed in the context of comparative studies in mammalian model systems and vertebrate species from different lineages.

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