Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm

1993 ◽  
Vol 265 (3) ◽  
pp. C834-C841 ◽  
Author(s):  
B. J. Petrof ◽  
H. H. Stedman ◽  
J. B. Shrager ◽  
J. Eby ◽  
H. L. Sweeney ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Contractile Function ◽  
Isometric Tension ◽  
Energy Requirements ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Type I ◽  
Muscle Degeneration ◽  
Cellular Energy

The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements.

scholarly journals ProNGF/p75NTR Axis Drives Fiber Type Specification by Inducing the Fast-Glycolytic Phenotype in Mouse Skeletal Muscle Cells

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2232
Author(s):  
Valentina Pallottini ◽  
Mayra Colardo ◽  
Claudia Tonini ◽  
Noemi Martella ◽  
Georgios Strimpakos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myogenic Differentiation ◽  
Fiber Type ◽  
Pcr Analysis ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Muscle Physiology

Despite its undisputable role in the homeostatic regulation of the nervous system, the nerve growth factor (NGF) also governs the relevant cellular processes in other tissues and organs. In this study, we aimed at assessing the expression and the putative involvement of NGF signaling in skeletal muscle physiology. To reach this objective, we employed satellite cell-derived myoblasts as an in vitro culture model. In vivo experiments were performed on Tibialis anterior from wild-type mice and an mdx mouse model of Duchenne muscular dystrophy. Targets of interest were mainly assessed by means of morphological, Western blot and qRT-PCR analysis. The results show that proNGF is involved in myogenic differentiation. Importantly, the proNGF/p75NTR pathway orchestrates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain and that of oxidative markers. Concurrently, proNGF/p75NTR activation facilitates the induction of fast myosin heavy chain and of fast/glycolytic markers. Furthermore, we also provided evidence that the oxidative metabolism is impaired in mdx mice, and that these alterations are paralleled by a prominent buildup of proNGF and p75NTR. These findings underline that the proNGF/p75NTR pathway may play a crucial role in fiber type determination and suggest its prospective modulation as an innovative therapeutic approach to counteract muscle disorders.

scholarly journals A screen for genetic loci required for body-wall muscle development during embryogenesis in Caenorhabditis elegans.

Genetics ◽  
1994 ◽  
Vol 137 (2) ◽  
pp. 483-498
Author(s):  
J Ahnn ◽  
A Fire
Keyword(s):  
Caenorhabditis Elegans ◽  
Myosin Heavy Chain ◽  
Muscle Cell ◽  
Heavy Chain ◽  
Body Wall ◽  
Muscle Development ◽  
Contractile Function ◽  
The Body ◽  
Body Wall Muscle ◽  
Genetic Loci

Abstract We have used available chromosomal deficiencies to screen for genetic loci whose zygotic expression is required for formation of body-wall muscle cells during embryogenesis in Caenorhabditis elegans. To test for muscle cell differentiation we have assayed for both contractile function and the expression of muscle-specific structural proteins. Monoclonal antibodies directed against two myosin heavy chain isoforms, the products of the unc-54 and myo-3 genes, were used to detect body-wall muscle differentiation. We have screened 77 deficiencies, covering approximately 72% of the genome. Deficiency homozygotes in most cases stain with antibodies to the body-wall muscle myosins and in many cases muscle contractile function is observed. We have identified two regions showing distinct defects in myosin heavy chain gene expression. Embryos homozygous for deficiencies removing the left tip of chromosome V fail to accumulate the myo-3 and unc-54 products, but express antigens characteristic of hypodermal, pharyngeal and neural development. Embryos lacking a large region on chromosome III accumulate the unc-54 product but not the myo-3 product. We conclude that there exist only a small number of loci whose zygotic expression is uniquely required for adoption of a muscle cell fate.

Force-velocity and force-power properties of single muscle fibers from elite master runners and sedentary men

1996 ◽  
Vol 271 (2) ◽  
pp. C676-C683 ◽  
Author(s):  
J. J. Widrick ◽  
S. W. Trappe ◽  
D. L. Costill ◽  
R. H. Fitts
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Power Output ◽  
Peak Power ◽  
Isometric Force ◽  
Peak Force ◽  
Peak Power Output ◽  
Type I ◽  
Shortening Velocity ◽  
Force Velocity

Gastrocnemius muscle fiber bundles were obtained by needle biopsy from five middle-aged sedentary men (SED group) and six age-matched endurance-trained master runners (RUN group). A single chemically permeabilized fiber segment was mounted between a force transducer and a position motor, subjected to a series of isotonic contractions at maximal Ca2+ activation (15 degrees C), and subsequently run on a 5% polyacrylamide gel to determine myosin heavy chain composition. The Hill equation was fit to the data obtained for each individual fiber (r2 > or = 0.98). For the SED group, fiber force-velocity parameters varied (P < 0.05) with fiber myosin heavy chain expression as follows: peak force, no differences: peak tension (force/fiber cross-sectional area), type IIx > type IIa > type I; maximal shortening velocity (Vmax, defined as y-intercept of force-velocity relationship), type IIx = type IIa > type I; a/Pzero (where a is a constant with dimensions of force and Pzero is peak isometric force), type IIx > type IIa > type I. Consequently, type IIx fibers produced twice as much peak power as type IIa fibers, whereas type IIa fibers produced about five times more peak power than type I fibers. RUN type I and IIa fibers were smaller in diameter and produced less peak force than SED type I and IIa fibers. The absolute peak power output of RUN type I and IIa fibers was 13 and 27% less, respectively, than peak power of similarly typed SED fibers. However, type I and IIa Vmax and a/Pzero were not different between the SED and RUN groups, and RUN type I and IIa power deficits disappeared after power was normalized for differences in fiber diameter. Thus the reduced absolute peak power output of the type I and IIa fibers from the master runners was a result of the smaller diameter of these fibers and a corresponding reduction in their peak isometric force production. This impairment in absolute peak power production at the single fiber level may be in part responsible for the reduced in vivo power output previously observed for endurance-trained athletes.

scholarly journals The Drosophila indirect flight muscle myosin heavy chain isoform is insufficient to transform the jump muscle into a highly stretch-activated muscle type

2017 ◽  
Vol 312 (2) ◽  
pp. C111-C118 ◽  
Author(s):  
Cuiping Zhao ◽  
Douglas M. Swank
Keyword(s):  
Power Generation ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Flight Muscle ◽  
Fold Increase ◽  
Isometric Tension ◽  
Indirect Flight Muscle ◽  
Muscle Type ◽  
Myosin Heavy Chain Isoform ◽  
Muscle Types

Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production ( FSA), whereas the jump muscle produces only minimal FSA. We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher FSA, we substituted the IFM MHC isoform (IFI) into the jump muscle. Surprisingly, we found that IFI only caused a 1.7-fold increase in FSA, less than half the increase previously observed with EMB, and only at a high Pi concentration, 16 mM. This IFI-induced FSA is much less than what occurs in IFM, relative to isometric tension, and did not enable positive cyclical power generation by the jump muscle. Both isometric tension and FSA of control fibers decreased with increasing Pi concentration. However, for IFI-expressing fibers, only isometric tension decreased. The rate of FSA generation was ~1.5-fold faster for IFI fibers than control fibers, and both rates were Pi dependent. We conclude that MHC isoforms can alter FSA and hence cyclical power generation but that isoforms can only endow a muscle type with moderate FSA. Highly SA muscle types, such as IFM, likely use a different or additional mechanism.

Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers

1996 ◽  
Vol 81 (6) ◽  
pp. 2540-2546 ◽  
Author(s):  
Robert J. Talmadge ◽  
Roland R. Roy ◽  
V. Reggie Edgerton
Keyword(s):  
Myosin Heavy Chain ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
De Novo ◽  
Weight Bearing ◽  
Muscle Fibers ◽  
Myosin Heavy Chain Isoforms ◽  
Hindlimb Suspension ◽  
Type I ◽  
Rat Soleus Muscle

Talmadge, Robert J., Roland R. Roy, and V. Reggie Edgerton.Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers. J. Appl. Physiol. 81(6): 2540–2546, 1996.—The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.

Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia

2001 ◽  
Vol 90 (6) ◽  
pp. 2508-2513 ◽  
Author(s):  
Thomas L. Clanton ◽  
Valerie P. Wright ◽  
Peter J. Reiser ◽  
Paul F. Klawitter ◽  
Nanduri R. Prabhakar
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Intermittent Hypoxia ◽  
Contractile Function ◽  
Myosin Heavy Chain Isoforms ◽  
Adaptive Responses ◽  
Low Frequencies ◽  
Myosin Heavy Chain Isoform ◽  
Obstructive Sleep

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20–36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress ( P < 0.005), twitch half-relaxation time ( P < 0.02), and tetanic stress at 20 or 30 Hz ( P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals ( P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans

1997 ◽  
Vol 273 (4) ◽  
pp. E790-E800 ◽  
Author(s):  
P. Balagopal ◽  
Olav E. Rooyackers ◽  
Deborah B. Adey ◽  
Philip A. Ades ◽  
K. Sreekumaran Nair
Keyword(s):  
Myosin Heavy Chain ◽  
Old Age ◽  
Muscle Mass ◽  
Heavy Chain ◽  
Contractile Function ◽  
Contractile Protein ◽  
Whole Body ◽  
Synthesis Rate ◽  
Sarcoplasmic Protein ◽  
Chain Synthesis

A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synthesis of this protein decreases in sarcopenia. The fractional synthesis rate of myosin heavy chain was measured simultaneously with rates of mixed muscle and sarcoplasmic proteins from the increment of [13C]leucine in these proteins purified from serial needle biopsy samples taken from 24 subjects (age: from 20 to 92 yr) during a primed continuous infusion ofl-[1-13C]leucine. A decline in synthesis rate of mixed muscle protein ( P < 0.01) and whole body protein ( P < 0.01) was observed from young to middle age with no further change with advancing age. An age-related decline of myosin heavy-chain synthesis rate was also observed ( P < 0.01), with progressive decline occurring from young, through middle, to old age. However, sarcoplasmic protein synthesis did not decline with age. Myosin heavy-chain synthesis rate was correlated with measures of muscle strength ( P < 0.05), circulating insulin-like growth factor I ( P < 0.01), and dehydroepiandrosterone sulfate ( P < 0.05) in men and women and free testosterone levels in men ( P < 0.01). A decline in the synthesis rate of myosin heavy chain implies a decreased ability to remodel this important muscle contractile protein and likely contributes to the declining muscle mass and contractile function in the elderly.

Myosin heavy chain composition of skeletal muscles in young rats growing under hypobaric hypoxia conditions

2000 ◽  
Vol 88 (2) ◽  
pp. 479-486 ◽  
Author(s):  
A. X. Bigard ◽  
H. Sanchez ◽  
O. Birot ◽  
B. Serrurier
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Wheel Running ◽  
Barometric Pressure ◽  
Major Influence ◽  
Type I ◽  
Running Activity ◽  
Equivalent Quantity ◽  
Chain Composition ◽  
Myosin Heavy Chain Composition

This study investigated the effects of voluntary wheel running on the myosin heavy chain (MHC) composition of the soleus (Sol) and plantaris muscles (Pla) in rats developing under hypobaric choronic hypoxia (CH) conditions during 4 wk in comparison with those of control rats maintained under local barometric pressure conditions (C) or rats pair-fed an equivalent quantity of food to that consumed by CH animals (PF). Compared with C animals, sedentary rats subjected to CH conditions showed a significant decrease in type I MHC in Sol (−12%, P < 0.01). Although strongly decreased under hypoxia, spontaneous running activity increased the expression of type I MHC ( P < 0.01) so that no difference in the MHC profile of Sol was shown between CH active and C active rats. The MHC distribution in Sol of PF rats was not significantly different from that found in C animals. CH resulted in a significant decrease in type I ( P < 0.01) and type IIA ( P < 0.005) MHC, concomitant with an increase in type IIB MHC in Pla ( P < 0.001), compared with C and PF animals. In contrast to results in Sol muscle, this slow-to-fast shift in the MHC profile was unaffected by spontaneous running activity. These results suggest that running exercise suppresses the hypoxia-induced slow-to-fast transition in the MHC expression in Sol muscles only. The hypoxia-induced decrease in food intake has no major influence on MHC expression in developing rats.

Role of USF1 phosphorylation on cardiac α-myosin heavy chain promoter activity

2002 ◽  
Vol 283 (1) ◽  
pp. H213-H219 ◽  
Author(s):  
Qianxun Xiao ◽  
Agnes Kenessey ◽  
Kaie Ojamaa
Keyword(s):  
Protein Kinase ◽  
Myosin Heavy Chain ◽  
Molecular Mechanism ◽  
Heavy Chain ◽  
Promoter Activity ◽  
Cardiac Myocyte ◽  
Contractile Function ◽  
Contractile Activity ◽  
Cell Mass ◽  
Two Dimensional Gel Electrophoresis

Contractile activity of the cardiac myocyte is required for maintaining cell mass and phenotype, including expression of the cardiac-specific α-myosin heavy chain (α-MHC) gene. An E-box hemodynamic response element (HME) located at position −47 within the α-MHC promoter is both necessary and sufficient to confer contractile responsiveness to the gene and has been shown to bind upstream stimulatory factor-1 (USF1). When studied in spontaneously contracting cardiac myocytes, there is enhanced binding of USF1 to the HME compared with quiescent cells, which correlates with a threefold increase in α-MHC promoter activity. A molecular mechanism by which contractile function modulates α-MHC transcriptional activity may involve signaling via phosphorylation of USF1. The present studies showed that purified rat USF1 was phosphorylated in vitro by protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) but not casein kinase II. Phosphorylated USF1 by either PKC or PKA had increased DNA binding activity to the HME. PKC-mediated phosphorylation also leads to the formation of USF1 multimers as assessed by gel shift assay. Analysis of in vivo phosphorylated nuclear proteins from cultured ventricular myocytes showed that USF1 was phosphorylated, and resolution by two-dimensional gel electrophoresis identified at least two distinct phosphorylated USF1 molecules. These results suggest that endogenous kinases can covalently modify USF1 and provide a potential molecular mechanism by which the contractile stimulus mediates changes in myocyte gene transcription.

Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice

1996 ◽  
Vol 271 (3) ◽  
pp. R688-R695 ◽  
Author(s):  
J. L. Wiedenman ◽  
G. L. Tsika ◽  
L. Gao ◽  
J. J. McCarthy ◽  
I. D. Rivera-Rivera ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Specific Activity ◽  
Fiber Type ◽  
Regulatory Element ◽  
Histochemical Staining ◽  
Regulatory Sequences ◽  
Type I ◽  
Adult Mice ◽  
Mechanical Overload

The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of mechanical overload have not been identified as yet. To delineate regulatory sequences that are required for mechanical overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by mechanical overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by mechanical overload in fast- and slow-twitch muscles.

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