To see the other types of publications on this topic, follow the link: Skeletal muscle myocytes.
Journal articles on the topic 'Skeletal muscle myocytes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Skeletal muscle myocytes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Raeker, Maide Ö., and Mark W. Russell. "Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos." Journal of Biomedicine and Biotechnology 2011 (2011): 1–15. http://dx.doi.org/10.1155/2011/479135.
Full textAbstract:
During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues.
2
Powers, Scott K. "Exercise: Teaching myocytes new tricks." Journal of Applied Physiology 123, no. 2 (August 1, 2017): 460–72. http://dx.doi.org/10.1152/japplphysiol.00418.2017.
Full textAbstract:
Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial function due to increased mitochondrial protein expression and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as “exercise preconditioning.” As few as 3–5 consecutive days of endurance exercise training result in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion-induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of cardiac and skeletal muscle fibers; these studies are important, because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the development of exercise-induced protection of cardiac myocytes and skeletal muscle fibers and highlights the putative mechanisms responsible for exercise-induced protection in the heart and skeletal muscles.
3
Himeda, Charis L., Jeffrey A. Ranish, and Stephen D. Hauschka. "Quantitative Proteomic Identification of MAZ as a Transcriptional Regulator of Muscle-Specific Genes in Skeletal and Cardiac Myocytes." Molecular and Cellular Biology 28, no. 20 (August 18, 2008): 6521–35. http://dx.doi.org/10.1128/mcb.00306-08.
Full textAbstract:
ABSTRACT We identified a conserved sequence within the Muscle creatine kinase (MCK) promoter that is critical for high-level activity in skeletal and cardiac myocytes (MCK Promoter Element X [MPEX]). After selectively enriching for MPEX-binding factor(s) (MPEX-BFs), ICAT-based quantitative proteomics was used to identify MPEX-BF candidates, one of which was MAZ (Myc-associated zinc finger protein). MAZ transactivates the MCK promoter and binds the MPEX site in vitro, and chromatin immunoprecipitation analysis demonstrates enrichment of MAZ at the endogenous MCK promoter and other muscle gene promoters (Skeletal α-actin, Desmin, and α-Myosin heavy chain) in skeletal and cardiac myocytes. Consistent with its role in muscle gene transcription, MAZ transcripts and DNA-binding activity are upregulated during skeletal myocyte differentiation. Furthermore, MAZ was shown to bind numerous sequences (e.g., CTCCTCCC and CTCCACCC) that diverge from the GA box binding motif. Alternate motifs were identified in many muscle promoters, including Myogenin and MEF2C, and one motif was shown to be critical for Six4 promoter activity in both skeletal and cardiac myocytes. Interestingly, MAZ occupies and is able to transactivate the Six4 promoter in skeletal but not cardiac myocytes. Taken together, these findings are consistent with a previously unrecognized role for MAZ in muscle gene regulation.
4
Amin, Rajesh H., Suresh T. Mathews, Heidi S. Camp, Liyun Ding, and Todd Leff. "Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance." American Journal of Physiology-Endocrinology and Metabolism 298, no. 1 (January 2010): E28—E37. http://dx.doi.org/10.1152/ajpendo.00446.2009.
Full textAbstract:
The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ plays a key role in regulating whole body glucose homeostasis and insulin sensitivity. Although it is expressed most highly in adipose, it is also present at lower levels in many tissues, including skeletal muscle. The role muscle PPARγ plays in metabolic regulation and in mediating the antidiabetic effects of the thiazolidinediones is not understood. The goal of this work was to examine the molecular and physiological effects of PPARγ activation in muscle cells. We found that pharmacological activation of PPARγ in primary cultured myocytes, and genetic activation of muscle PPARγ in muscle tissue of transgenic mice, induced the production of adiponectin directly from muscle cells. This muscle-produced adiponectin was functional and capable of stimulating adiponectin signaling in myocytes. In addition, elevated skeletal muscle PPARγ activity in transgenic mice provided a significant protection from high-fat diet-induced insulin resistance and associated changes in muscle phenotype, including reduced myocyte lipid content and an increase in the proportion of oxidative muscle fiber types. Our findings demonstrate that PPARγ activation in skeletal muscle can have a significant protective effect on whole body glucose homeostasis and insulin resistance and that myocytes can produce and secrete functional adiponectin in a PPARγ-dependent manner. We propose that activation of PPARγ in myocytes induces a local production of adiponectin that acts on muscle tissue to improve insulin sensitivity.
5
Bers, D. M., and V. M. Stiffel. "Ratio of ryanodine to dihydropyridine receptors in cardiac and skeletal muscle and implications for E-C coupling." American Journal of Physiology-Cell Physiology 264, no. 6 (June 1, 1993): C1587—C1593. http://dx.doi.org/10.1152/ajpcell.1993.264.6.c1587.
Full textAbstract:
We measured dihydropyridine receptor (DHPR) and ryanodine receptor (RYR) density in isolated ventricular myocytes from rabbits, rats, ferrets, and guinea pigs and also from rabbit ventricular homogenate, skeletal muscle homogenate, and isolated triads. In skeletal muscle homogenate and triads the RYR/DHPR ratio was 0.7 and 0.52, respectively. This stoichiometry is reasonably consistent with excitation-contraction (E-C) coupling models in skeletal muscle where the DHPR molecule itself may transmit the signal for Ca release to the sarcoplasmic reticulum (SR) and with the molecular arrangement proposed for toadfish swimbladder from ultrastructural studies by B. A. Block, T. Imagawa, K. P. Campbell, and C. Franzini-Armstrong. (J. Cell Biol. 107: 2587-2600, 1988). That is, there could be approximately two RYR for each four DHPR or two RYR feet per DHPR tetrad in an organized array (assuming 1 high-affinity RYR/foot and 4 DHPR/tetrad). The fraction of rabbit ventricular protein that is cardiac myocyte protein was also estimated (< or = 55-62%), assuming that RYR and DHPR are useful but not exclusive markers for myocytes in the ventricle. In cardiac myocytes the RYR/DHPR was much higher than in skeletal muscle and varied among different mammalian myocytes. The RYR/DHPR ratios were 3.7 in rabbit, 4.3 in guinea pig, 7.3 in rat, and 10.2 in ferret myocytes. In contrast to skeletal muscle, these results indicate that there are many more RYR feet per DHPR in cardiac muscle, and this ratio depends on species (i.e., 4-10 times and would be 4 times higher still per putative DHPR tetrad if that structure exists in mammalian heart).(ABSTRACT TRUNCATED AT 250 WORDS)
6
Dubé, John J., Mitch T. Sitnick, Gabriele Schoiswohl, Rachel C. Wills, Mahesh K. Basantani, Lingzhi Cai, Thomas Pulinilkunnil, and Erin E. Kershaw. "Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice." American Journal of Physiology-Endocrinology and Metabolism 308, no. 10 (May 15, 2015): E879—E890. http://dx.doi.org/10.1152/ajpendo.00530.2014.
Full textAbstract:
Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triacylglycerol hydrolysis in virtually all cells, including adipocytes and skeletal myocytes, and hence, plays a critical role in mobilizing fatty acids. Global ATGL deficiency promotes skeletal myopathy and exercise intolerance in mice and humans, and yet the tissue-specific contributions to these phenotypes remain unknown. The goal of this study was to determine the relative contribution of ATGL-mediated triacylglycerol hydrolysis in adipocytes vs. skeletal myocytes to acute exercise performance. To achieve this goal, we generated murine models with adipocyte- and skeletal myocyte-specific targeted deletion of ATGL. We then subjected untrained mice to acute peak and submaximal exercise interventions and assessed exercise performance and energy substrate metabolism. Impaired ATGL-mediated lipolysis within adipocytes reduced peak and submaximal exercise performance, reduced peripheral energy substrate availability, shifted energy substrate preference toward carbohydrate oxidation, and decreased HSL Ser660 phosphorylation and mitochondrial respiration within skeletal muscle. In contrast, impaired ATGL-mediated lipolysis within skeletal myocytes was not sufficient to reduce peak and submaximal exercise performance or peripheral energy substrate availability and instead tended to enhance metabolic flexibility during peak exercise. Furthermore, the expanded intramyocellular triacylglycerol pool in these mice was reduced following exercise in association with preserved HSL phosphorylation, suggesting that HSL may compensate for impaired ATGL action in skeletal muscle during exercise. These data suggest that adipocyte rather than skeletal myocyte ATGL-mediated lipolysis plays a greater role during acute exercise in part because of compensatory mechanisms that maintain lipolysis in muscle, but not adipose tissue, when ATGL is absent.
7
Hara, Mie, Shinsuke Yuasa, Kenichiro Shimoji, Takeshi Onizuka, Nozomi Hayashiji, Yohei Ohno, Takahide Arai, et al. "G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation." Journal of Experimental Medicine 208, no. 4 (March 21, 2011): 715–27. http://dx.doi.org/10.1084/jem.20101059.
Full textAbstract:
After skeletal muscle injury, neutrophils, monocytes, and macrophages infiltrate the damaged area; this is followed by rapid proliferation of myoblasts derived from muscle stem cells (also called satellite cells). Although it is known that inflammation triggers skeletal muscle regeneration, the underlying molecular mechanisms remain incompletely understood. In this study, we show that granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is expressed in developing somites. G-CSFR and G-CSF were expressed in myoblasts of mouse embryos during the midgestational stage but not in mature myocytes. Furthermore, G-CSFR was specifically but transiently expressed in regenerating myocytes present in injured adult mouse skeletal muscle. Neutralization of endogenous G-CSF with a blocking antibody impaired the regeneration process, whereas exogenous G-CSF supported muscle regeneration by promoting the proliferation of regenerating myoblasts. Furthermore, muscle regeneration was markedly impaired in G-CSFR–knockout mice. These findings indicate that G-CSF is crucial for skeletal myocyte development and regeneration and demonstrate the importance of inflammation-mediated induction of muscle regeneration.
8
Asakura, Atsushi, Patrick Seale, Adele Girgis-Gabardo, and Michael A. Rudnicki. "Myogenic specification of side population cells in skeletal muscle." Journal of Cell Biology 159, no. 1 (October 14, 2002): 123–34. http://dx.doi.org/10.1083/jcb.200202092.
Full textAbstract:
Skeletal muscle contains myogenic progenitors called satellite cells and muscle-derived stem cells that have been suggested to be pluripotent. We further investigated the differentiation potential of muscle-derived stem cells and satellite cells to elucidate relationships between these two populations of cells. FACS® analysis of muscle side population (SP) cells, a fraction of muscle-derived stem cells, revealed expression of hematopoietic stem cell marker Sca-1 but did not reveal expression of any satellite cell markers. Muscle SP cells were greatly enriched for cells competent to form hematopoietic colonies. Moreover, muscle SP cells with hematopoietic potential were CD45 positive. However, muscle SP cells did not differentiate into myocytes in vitro. By contrast, satellite cells gave rise to myocytes but did not express Sca-1 or CD45 and never formed hematopoietic colonies. Importantly, muscle SP cells exhibited the potential to give rise to both myocytes and satellite cells after intramuscular transplantation. In addition, muscle SP cells underwent myogenic specification after co-culture with myoblasts. Co-culture with myoblasts or forced expression of MyoD also induced muscle differentiation of muscle SP cells prepared from mice lacking Pax7 gene, an essential gene for satellite cell development. Therefore, these data document that satellite cells and muscle-derived stem cells represent distinct populations and demonstrate that muscle-derived stem cells have the potential to give rise to myogenic cells via a myocyte-mediated inductive interaction.
9
Murray, Jennifer, and Janice M. Huss. "Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway." American Journal of Physiology-Cell Physiology 301, no. 3 (September 2011): C630—C645. http://dx.doi.org/10.1152/ajpcell.00033.2011.
Full textAbstract:
Myocyte differentiation involves complex interactions between signal transduction pathways and transcription factors. The estrogen-related receptors (ERRs) regulate energy substrate uptake, mitochondrial respiration, and biogenesis and may target structural gene programs in striated muscle. However, ERRα's role in regulating myocyte differentiation is not known. ERRα and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) are coordinately upregulated with metabolic and skeletal muscle-specific genes early in myogenesis. We analyzed effects of ERRα overexpression and loss of function in myogenic models. In C2C12 myocytes ERRα overexpression accelerated differentiation, whereas XCT790 treatment delayed myogenesis and resulted in myotubes with fewer mitochondria and disorganized sarcomeres. ERRα−/− primary myocytes showed delayed myogenesis, resulting in structurally immature myotubes with reduced sarcomeric assembly and mitochondrial function. However, sarcomeric and metabolic gene expression was unaffected or upregulated in ERRα−/− cells. Instead, ERRα−/− myocytes exhibited aberrant ERK activation early in myogenesis, consistent with delayed myotube formation. XCT790 treatment also increased ERK phosphorylation in C2C12, whereas ERRα overexpression decreased early ERK activation, consistent with the opposing effects of these treatments on differentiation. The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα−/− myocytes and in XCT790-treated C2C12. The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5′ regulatory region during early differentiation in C2C12 myocytes. Finally, treatment of ERRα−/− myocytes with MEK inhibitors rescued normal ERK signaling and myogenesis. Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling.
10
Clegg, C. H., and S. D. Hauschka. "Heterokaryon analysis of muscle differentiation: regulation of the postmitotic state." Journal of Cell Biology 105, no. 2 (August 1, 1987): 937–47. http://dx.doi.org/10.1083/jcb.105.2.937.
Full textAbstract:
MM14 mouse myoblasts withdraw irreversibly from the cell cycle and become postmitotic within a few hours of being deprived of fibroblast growth factor (Clegg, C. H., T. A. Linkhart, B. B. Olwin, and S. D. Hauschka, 1987, J. Cell Biol., 105:949-956). To examine the mechanisms that may regulate this developmental state of skeletal muscle, we tested the mitogen responsiveness of various cell types after their polyethylene glycol-mediated fusion with post-mitotic myocytes. Heterokaryons containing myocytes and quiescent nonmyogenic cells such as 3T3, L cell, and a differentiation-defective myoblast line (DD-1) responded to mitogen-rich medium by initiating DNA synthesis. Myonuclei replicated DNA and reexpressed thymidine kinase. In contrast, (myocyte x G1 myoblast) heterokaryons failed to replicate DNA in mitogen-rich medium and became postmitotic. This included cells with a nuclear ratio of three myoblasts to one myocyte. Proliferation dominance in (myocyte x 3T3 cell) and (myocyte x DD-1) heterokaryons was conditionally regulated by the timing of mitogen treatment; such cells became postmitotic when mitogen exposure was delayed for as little as 6 h after cell fusion. In addition, (myocyte x DD-1) heterokaryons expressed a muscle-specific trait and lost epidermal growth factor receptors when they became postmitotic. These results demonstrate that DNA synthesis is not irreversibly blocked in skeletal muscle; myonuclei readily express proliferation-related functions when provided with a mitogenic signal. Rather, myocyte-specific repression of DNA synthesis in heterokaryons argues that the postmitotic state of skeletal muscle is regulated by diffusible factors that inhibit processes of cellular mitogenesis.
11
Herring, B. Paul, Shelley Dixon, and Patricia J. Gallagher. "Smooth muscle myosin light chain kinase expression in cardiac and skeletal muscle." American Journal of Physiology-Cell Physiology 279, no. 5 (November 1, 2000): C1656—C1664. http://dx.doi.org/10.1152/ajpcell.2000.279.5.c1656.
Full textAbstract:
The purpose of this study was to characterize myosin light chain kinase (MLCK) expression in cardiac and skeletal muscle. The only classic MLCK detected in cardiac tissue, purified cardiac myocytes, and in a cardiac myocyte cell line (AT1) was identical to the 130-kDa smooth muscle MLCK (smMLCK). A complex pattern of MLCK expression was observed during differentiation of skeletal muscle in which the 220-kDa-long or “nonmuscle” form of MLCK is expressed in undifferentiated myoblasts. Subsequently, during myoblast differentiation, expression of the 220-kDa MLCK declines and expression of this form is replaced by the 130-kDa smMLCK and a skeletal muscle-specific isoform, skMLCK in adult skeletal muscle. These results demonstrate that the skMLCK is the only tissue-specific MLCK, being expressed in adult skeletal muscle but not in cardiac, smooth, or nonmuscle tissues. In contrast, the 130-kDa smMLCK is ubiquitous in all adult tissues, including skeletal and cardiac muscle, demonstrating that, although the 130-kDa smMLCK is expressed at highest levels in smooth muscle tissues, it is not a smooth muscle-specific protein.
12
Amacher, S. L., J. N. Buskin, and S. D. Hauschka. "Multiple regulatory elements contribute differentially to muscle creatine kinase enhancer activity in skeletal and cardiac muscle." Molecular and Cellular Biology 13, no. 5 (May 1993): 2753–64. http://dx.doi.org/10.1128/mcb.13.5.2753-2764.1993.
Full textAbstract:
We have used transient transfections in MM14 skeletal muscle cells, newborn rat primary ventricular myocardiocytes, and nonmuscle cells to characterize regulatory elements of the mouse muscle creatine kinase (MCK) gene. Deletion analysis of MCK 5'-flanking sequence reveals a striated muscle-specific, positive regulatory region between -1256 and -1020. A 206-bp fragment from this region acts as a skeletal muscle enhancer and confers orientation-dependent activity in myocardiocytes. A 110-bp enhancer subfragment confers high-level expression in skeletal myocytes but is inactive in myocardiocytes, indicating that skeletal and cardiac muscle MCK regulatory sites are distinguishable. To further delineate muscle regulatory sequences, we tested six sites within the MCK enhancer for their functional importance. Mutations at five sites decrease expression in skeletal muscle, cardiac muscle, and nonmuscle cells. Mutations at two of these sites, Left E box and MEF2, cause similar decreases in all three cell types. Mutations at three sites have larger effects in muscle than nonmuscle cells; an A/T-rich site mutation has a pronounced effect in both striated muscle types, mutations at the MEF1 (Right E-box) site are relatively specific to expression in skeletal muscle, and mutations at the CArG site are relatively specific to expression in cardiac muscle. Changes at the AP2 site tend to increase expression in muscle cells but decrease it in nonmuscle cells. In contrast to reports involving cotransfection of 10T1/2 cells with plasmids expressing the myogenic determination factor MyoD, we show that the skeletal myocyte activity of multimerized MEF1 sites is 30-fold lower than that of the 206-bp enhancer. Thus, MyoD binding sites alone are not sufficient for high-level expression in skeletal myocytes containing endogenous levels of MyoD and other myogenic determination factors.
13
Amacher, S. L., J. N. Buskin, and S. D. Hauschka. "Multiple regulatory elements contribute differentially to muscle creatine kinase enhancer activity in skeletal and cardiac muscle." Molecular and Cellular Biology 13, no. 5 (May 1993): 2753–64. http://dx.doi.org/10.1128/mcb.13.5.2753.
Full textAbstract:
We have used transient transfections in MM14 skeletal muscle cells, newborn rat primary ventricular myocardiocytes, and nonmuscle cells to characterize regulatory elements of the mouse muscle creatine kinase (MCK) gene. Deletion analysis of MCK 5'-flanking sequence reveals a striated muscle-specific, positive regulatory region between -1256 and -1020. A 206-bp fragment from this region acts as a skeletal muscle enhancer and confers orientation-dependent activity in myocardiocytes. A 110-bp enhancer subfragment confers high-level expression in skeletal myocytes but is inactive in myocardiocytes, indicating that skeletal and cardiac muscle MCK regulatory sites are distinguishable. To further delineate muscle regulatory sequences, we tested six sites within the MCK enhancer for their functional importance. Mutations at five sites decrease expression in skeletal muscle, cardiac muscle, and nonmuscle cells. Mutations at two of these sites, Left E box and MEF2, cause similar decreases in all three cell types. Mutations at three sites have larger effects in muscle than nonmuscle cells; an A/T-rich site mutation has a pronounced effect in both striated muscle types, mutations at the MEF1 (Right E-box) site are relatively specific to expression in skeletal muscle, and mutations at the CArG site are relatively specific to expression in cardiac muscle. Changes at the AP2 site tend to increase expression in muscle cells but decrease it in nonmuscle cells. In contrast to reports involving cotransfection of 10T1/2 cells with plasmids expressing the myogenic determination factor MyoD, we show that the skeletal myocyte activity of multimerized MEF1 sites is 30-fold lower than that of the 206-bp enhancer. Thus, MyoD binding sites alone are not sufficient for high-level expression in skeletal myocytes containing endogenous levels of MyoD and other myogenic determination factors.
14
Ojuka, Edward O., Terry E. Jones, Lorraine A. Nolte, May Chen, Brian R. Wamhoff, Michael Sturek, and John O. Holloszy. "Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+." American Journal of Physiology-Endocrinology and Metabolism 282, no. 5 (May 1, 2002): E1008—E1013. http://dx.doi.org/10.1152/ajpendo.00512.2001.
Full textAbstract:
There is evidence suggesting that adaptive increases in GLUT4 and mitochondria in skeletal muscle occur in parallel. It has been reported that raising cytosolic Ca2+ in myocytes induces increases in mitochondrial enzymes. In this study, we tested the hypothesis that an increase in cytosolic Ca2+ induces an increase in GLUT4. We found that raising cytosolic Ca2+ by exposing L6 myotubes to 5 mM caffeine for 3 h/day for 5 days induced increases in GLUT4 protein and in myocyte enhancer factor (MEF)2A and MEF2D, which are transcription factors involved in regulating GLUT4 expression. The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca2+ release, and completely blocked by KN93, an inhibitor of Ca2+-calmodulin-dependent protein kinase (CAMK). Caffeine also induced increases in MEF2A, MEF2D, and GLUT4 in rat epitrochlearis muscles incubated with caffeine in culture medium. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), which activates AMP-activated protein kinase (AMPK), also induced approximately twofold increases in GLUT4, MEF2A, and MEF2D in L6 myocytes. Our results provide evidence that increases in cytosolic Ca2+and activation of AMPK, both of which occur in exercising muscle, increase GLUT4 protein in myocytes and skeletal muscle. The data suggest that this effect of Ca2+ is mediated by activation of CAMK and indicate that MEF2A and MEF2D are involved in this adaptive response.
15
Nishizawa, Hitoshi, Morihiro Matsuda, Yukio Yamada, Kenichiro Kawai, Emi Suzuki, Makoto Makishima, Toshio Kitamura, and Iichiro Shimomura. "Musclin, a Novel Skeletal Muscle-derived Secretory Factor." Journal of Biological Chemistry 279, no. 19 (March 24, 2004): 19391–95. http://dx.doi.org/10.1074/jbc.c400066200.
Full textAbstract:
Skeletal muscle is involved in the homeostasis of glucose and lipid metabolism. We hypothesized that the skeletal muscle produces and secretes bioactive factor(s), similar to adipocytokines secreted by fat tissue. Here, we report the identification of a novel secretory factor, musclin, by signal sequence trap of mouse skeletal muscle cDNAs. Musclin cDNA encoded 130 amino acids, including NH2-terminal 30-amino acid signal sequence. Musclin protein contained a region homologous to natriuretic peptide family, and KKKR, a putative serine protease cleavage site, similar to the natriuretic peptide family. Full-length musclin protein and KKKR-dependent cleaved form were secreted in media of musclin cDNA-transfected mammalian cell cultures. Musclin mRNA was expressed almost exclusively in the skeletal muscle of mice. Musclin mRNA levels in skeletal muscle were markedly low in fasted, increased upon re-feeding, and were low in streptozotocin-treated insulin-deficient mice. Musclin mRNA expression was induced at late stage in the differentiation of C2C12 myocytes. In myocytes, insulin increased, while epinephrine, isoproterenol, and forskolin reduced musclin mRNA, all of which are known to increase the cellular content of cyclic AMP, a counter-regulator to insulin. Pathologically, overexpression of musclin mRNA was noted in the muscles of obese insulin-resistant KKAy mice. Functionally, recombinant musclin significantly attenuated insulin-stimulated glucose uptake and glycogen synthesis in myocytes. In conclusion, we identified musclin, a novel skeletal muscle-derived secretory factor. Musclin expression level is tightly regulated by nutritional changes and its physiological role could be linked to glucose metabolism.
16
VITADELLO, Maurizio, Pierangelo COLPO, and Luisa GORZA. "Rabbit cardiac and skeletal myocytes differ in constitutive and inducible expression of the glucose-regulated protein GRP94." Biochemical Journal 332, no. 2 (June 1, 1998): 351–59. http://dx.doi.org/10.1042/bj3320351.
Full textAbstract:
The glucose-regulated protein GRP94 is a stress-inducible glycoprotein that is known to be constitutively and ubiquitously expressed in the endoplasmic reticulum of mammalian cells. From a rabbit heart cDNA library we isolated four overlapping clones coding for the rabbit homologue of GRP94 mRNA. Northern blot analysis shows that a 3200 nt mRNA species corresponding to GRP94 mRNA is detectable in several tissues and it is 5-fold more abundant in the heart than in the skeletal muscle. Hybridization analysis in situ shows that GRP94 mRNA accumulates in cardiac myocytes, whereas in skeletal muscles it is not detectable in myofibres. A monoclonal antibody raised by using a 35 kDa recombinant GRP94 polypeptide as immunogen detects a single reactive polypeptide of 94 kDa in a Western blot of liver and heart homogenates and does not react with skeletal muscle homogenates. Conversely, GRP94 mRNA and protein are detectable in both cardiac and skeletal muscle myocytes of fetal and neonatal rabbits. After 24 h of endotoxin administration to adult rabbits, GRP94 mRNA accumulation increases 3-fold in both heart and skeletal muscle and it is followed by a comparable increase in protein accumulation. However, hybridization and immunohistochemistry in situ do not reveal any change in the expression of GRP94 mRNA and protein in skeletal muscle myocytes after endotoxin treatment. Thus skeletal muscle fibres display a unique regulation of the GRP94 gene, which is up-regulated during perinatal development, whereas in the adult animal it is apparently silent and not responsive to endotoxin treatment.
17
Testa, Marco, Bianca Rocca, Lucia Spath, Franco O. Ranelletti, Giovanna Petrucci, Giovanni Ciabattoni, Fabio Naro, Stefano Schiaffino, Massimo Volpe, and Carlo Reggiani. "Expression and activity of cyclooxygenase isoforms in skeletal muscles and myocardium of humans and rodents." Journal of Applied Physiology 103, no. 4 (October 2007): 1412–18. http://dx.doi.org/10.1152/japplphysiol.00288.2007.
Full textAbstract:
Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins (PGs). We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blotting, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscles from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly PGE2. The biosynthesis of PGE2 was reduced between 50 and 80% ( P < 0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE2 added to isolated skeletal muscle preparations from rodents did not affect contraction, whereas it significantly fastened relaxation of a slow type muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE2 appears to be the main product of COX activity in striated muscles.
18
Nakada, Satoshi, Yuri Yamashita, Seiya Akiba, Takeru Shima, and Eri Arikawa-Hirasawa. "Myocyte Culture with Decellularized Skeletal Muscle Sheet with Observable Interaction with the Extracellular Matrix." Bioengineering 9, no. 7 (July 12, 2022): 309. http://dx.doi.org/10.3390/bioengineering9070309.
Full textAbstract:
In skeletal muscles, muscle fibers are highly organized and bundled within the basement membrane. Several microfabricated substrate models have failed to mimic the macrostructure of native muscle, including various extracellular matrix (ECM) proteins. Therefore, we developed and evaluated a system using decellularized muscle tissue and mouse myoblasts C2C12 to analyze the interaction between native ECM and myocytes. Chicken skeletal muscle was sliced into sheets and decellularized to prepare decellularized skeletal muscle sheets (DSMS). C2C12 was then seeded and differentiated on DSMS. Immunostaining for ECM molecules was performed to examine the relationship between myoblast adhesion status, myotube orientation, and collagen IV orientation. Myotube survival in long-term culture was confirmed by calcein staining. C2C12 myoblasts adhered to scaffolds in DSMS and developed adhesion plaques and filopodia. Furthermore, C2C12 myotubes showed orientation along the ECM orientation within DSMS. Compared to plastic dishes, detachment was less likely to occur on DSMS, and long-term incubation was possible. This culture technique reproduces a cell culture environment reflecting the properties of living skeletal muscle, thereby allowing studies on the interaction between the ECM and myocytes.
19
Yin, Ming Zhe, Hae Jin Kim, Eun Yeong Suh, Yin Hua Zhang, Hae Young Yoo, and Sung Joon Kim. "Endurance exercise training restores atrophy-induced decreases of myogenic response and ionic currents in rat skeletal muscle artery." Journal of Applied Physiology 126, no. 6 (June 1, 2019): 1713–24. http://dx.doi.org/10.1152/japplphysiol.00962.2018.
Full textAbstract:
Atrophic limbs exhibit decreased blood flow and histological changes in the arteries perfusing muscles. However, the effect of atrophy on vascular smooth muscle function is poorly understood. Here, we investigated the effect of unilateral sciatic denervation on the myogenic response (MR) and the ionic currents in deep femoral artery (DFA) smooth muscles from Sprague-Dawley rats. Because denervated rats were capable of treadmill exercise (20 m/min, 30 min, 3 times/wk), the impact of exercise training on these effects was also assessed. Skeletal arteries were harvested 3 or 5 wk after surgery. Then skeletal arteries or myocytes were subjected to video analysis of pressurized artery, myography, whole-cell patch clamp, and real-time quantitative PCR to determine the effect of hindlimb paralysis in the presence/absence of exercise training on MR, contractility, ionic currents, and channel transcription, respectively. In sedentary rats, atrophy was associated with loss of MR in the DFA at 5 wk. The contralateral DFA had a normal MR. At 5 wk after surgery, DFA myocytes from the atrophic limbs exhibited depressed L-type Ca2+currents, GTPγS-induced transient receptor potential cation channel (TRPC)-like currents, 80 mM KCl-induced vasoconstriction, TRPC6 mRNA, and voltage-gated K+and inwardly rectifying K+currents. Exercise training abrogated the differences in all of these functions between atrophic side and contralateral side DFA myocytes. These results suggest that a probable increase in hemodynamic stimuli in skeletal artery smooth muscle plays an important role in maintaining MR and ionic currents in skeletal artery smooth muscle. This may also explain the observed benefits of exercise in patients with limb paralysis.NEW & NOTEWORTHY Myogenic responses (MRs) in rat skeletal arteries feeding the unilateral atrophic hindlimb were impaired. In addition, the L-type Ca2+channel current, the TRPC6-like current, and TRPC6 mRNA levels in the corresponding myocytes decreased. Voltage-gated K+channel currents and inwardly rectifying K+channel currents were also attenuated in atrophic side myocytes. Exercise training effectively abrogated electrophysiological dysfunction of atrophic side myocytes and prevented loss of the MR.
20
Carson, James A., and Frank W. Booth. "Effect of serum and mechanical stretch on skeletal α-actin gene regulation in cultured primary muscle cells." American Journal of Physiology-Cell Physiology 275, no. 6 (December 1, 1998): C1438—C1448. http://dx.doi.org/10.1152/ajpcell.1998.275.6.c1438.
Full textAbstract:
The purpose of this study was to determine whether mechanical stretch or serum availability alters pretranslational regulation of skeletal α-actin (SkA) in cultured striated muscle cells. Chicken primary skeletal myoblasts and cardiac myocytes were plated on collagenized Silastic membranes adherent to nylon supports and stretched 8–20% of initial length 96 h postplating. Serum dependence of SkA gene regulation was determined by maintaining differentiated muscle cells in growth/differentiation (G/D; skeletal myotubes, 10% horse serum-2% chick embryo extract; cardiac myocytes, 10% horse serum) or growth-limiting (G-L; 0.5% horse serum) medium. Skeletal myotubes had higher SkA mRNA and SkA promoter activity in G/D than in G-L medium. Cardiac myocyte SkA mRNA was higher in G-L than in G/D medium. Serum response factor (SRF) protein binding to serum response element 1 (SRE1) of SkA promoter increased in skeletal cultures in G/D compared with G-L medium. Western blot analysis demonstrated that increased SRF-SRE1 binding was due, in part, to increased SRF protein. Stretching skeletal myotubes in G-L medium reduced SkA mRNA and repressed SkA promoter activity. The first 100 bp of SkA promoter were sufficient for stretch-induced repression of SkA promoter activity, and an intact transcriptional enhancer factor 1 (TEF-1) binding site was necessary for this response. Serum and stretch appear to repress SkA promoter activity in skeletal myotubes through different DNA binding elements, the SRE1 and TEF-1 sites, respectively. Stretching increased SkA mRNA in cardiac myocytes in G-L medium but did not alter SkA mRNA level in cardiac cells in G/D medium. These results demonstrate that stretch and serum interact differently to alter SkA expression in cultured cardiac and skeletal muscle cells.
21
Ophoff, Jill, Karen Van Proeyen, Filip Callewaert, Karel De Gendt, Katrien De Bock, An Vanden Bosch, Guido Verhoeven, Peter Hespel, and Dirk Vanderschueren. "Androgen Signaling in Myocytes Contributes to the Maintenance of Muscle Mass and Fiber Type Regulation But Not to Muscle Strength or Fatigue." Endocrinology 150, no. 8 (August 1, 2009): 3558–66. http://dx.doi.org/10.1210/en.2008-1509.
Full textAbstract:
Muscle frailty is considered a major cause of disability in the elderly and chronically ill. However, the exact role of androgen receptor (AR) signaling in muscle remains unclear. Therefore, a postmitotic myocyte-specific AR knockout (mARKO) mouse model was created and investigated together with a mouse model with ubiquitous AR deletion. Muscles from mARKO mice displayed a marked reduction in AR protein (60–88%). Interestingly, body weights and lean body mass were lower in mARKO vs. control mice (−8%). The weight of the highly androgen-sensitive musculus levator ani was significantly reduced (−46%), whereas the weights of other peripheral skeletal muscles were not or only slightly reduced. mARKO mice had lower intra-abdominal fat but did not demonstrate a cortical or trabecular bone phenotype, indicating that selective ablation of the AR in myocytes affected male body composition but not skeletal homeostasis. Furthermore, muscle contractile performance in mARKO mice did not differ from their controls. Myocyte-specific AR ablation resulted in a conversion of fast toward slow fibers, without affecting muscle strength or fatigue. Similar results were obtained in ubiquitous AR deletion, showing lower body weight, whereas some but not all muscle weights were reduced. The percent slow fibers was increased, but no changes in muscle strength or fatigue could be detected. Together, our findings show that myocyte AR signaling contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. The levator ani weight remains the most sensitive and specific marker of AR-mediated anabolic action on muscle.
22
Masuzawa, Ryuichi, Kazuya Takahashi, Kazunori Takano, Ichizo Nishino, Toshiyuki Sakai, and Takeshi Endo. "DA-Raf and the MEK inhibitor trametinib reverse skeletal myocyte differentiation inhibition or muscle atrophy caused by myostatin and GDF11 through the non-Smad Ras–ERK pathway." Journal of Biochemistry 171, no. 1 (October 22, 2021): 109–22. http://dx.doi.org/10.1093/jb/mvab116.
Full textAbstract:
Abstract Myostatin (Mstn) and GDF11 are critical factors that are involved in muscle atrophy in the young and sarcopenia in the elderly, respectively. These TGF-β superfamily proteins activate not only Smad signalling but also non-Smad signalling including the Ras-mediated ERK pathway (Raf–MEK–ERK phosphorylation cascade). Although Mstn and GDF11 have been shown to induce muscle atrophy or sarcopenia by Smad2/3-mediated Akt inhibition, participation of the non-Smad Ras–ERK pathway in atrophy and sarcopenia has not been well determined. We show here that both Mstn and GDF11 prevented skeletal myocyte differentiation but that the MEK inhibitor U0126 or trametinib restored differentiation in Mstn- or GDF11-treated myocytes. These MEK inhibitors induced the expression of DA-Raf1 (DA-Raf), which is a dominant-negative antagonist of the Ras–ERK pathway. Exogenous expression of DA-Raf in Mstn- or GDF11-treated myocytes restored differentiation. Furthermore, administration of trametinib to aged mice resulted in an increase in myofiber size or recovery from muscle atrophy. The trametinib administration downregulated ERK activity in these muscles. These results imply that the Mstn/GDF11-induced Ras–ERK pathway plays critical roles in the inhibition of myocyte differentiation and muscle regeneration, which leads to muscle atrophy. Trametinib and similar approved drugs might be applicable to the treatment of muscle atrophy in sarcopenia or cachexia.
23
Werneck-de-Castro, Joao P., Tatiana L. Fonseca, Daniele L. Ignacio, Gustavo W. Fernandes, Cristina M. Andrade-Feraud, Lattoya J. Lartey, Marcelo B. Ribeiro, Miriam O. Ribeiro, Balazs Gereben, and Antonio C. Bianco. "Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes." Endocrinology 156, no. 10 (July 27, 2015): 3842–52. http://dx.doi.org/10.1210/en.2015-1246.
Full textAbstract:
The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers.
24
Markworth, James F., and David Cameron-Smith. "Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway." American Journal of Physiology-Cell Physiology 304, no. 1 (January 1, 2013): C56—C67. http://dx.doi.org/10.1152/ajpcell.00038.2012.
Full textAbstract:
Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro . C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF2α and PGE2; however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.
25
Tao, Yazhong, Ronald L. Neppl, Zhan-Peng Huang, Jianfu Chen, Ru-Hang Tang, Ru Cao, Yi Zhang, Suk-Won Jin, and Da-Zhi Wang. "The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly." Journal of Cell Biology 194, no. 4 (August 22, 2011): 551–65. http://dx.doi.org/10.1083/jcb.201010090.
Full textAbstract:
The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.
26
Suh, Dae Keun, Won-Young Lee, Woo Jin Yeo, Bong Soo Kyung, Koo Whang Jung, Hye Kyung Seo, Yong-Soo Lee, and Dong Won Suh. "A Novel Muscle Atrophy Mechanism: Myocyte Degeneration Due to Intracellular Iron Deprivation." Cells 11, no. 18 (September 13, 2022): 2853. http://dx.doi.org/10.3390/cells11182853.
Full textAbstract:
Muscle atrophy is defined as the progressive degeneration or shrinkage of myocytes and is triggered by factors such as aging, cancer, injury, inflammation, and immobilization. Considering the total amount of body iron stores and its crucial role in skeletal muscle, myocytes may have their own iron regulation mechanism. Although the detrimental effects of iron overload or iron deficiency on muscle function have been studied, the molecular mechanism of iron-dependent muscle atrophy has not been elucidated. Using human muscle tissues and in the mouse rotator cuff tear model, we confirmed an association between injury-induced iron depletion in myocytes and muscle atrophy. In differentiated C2C12 myotubes, the effects of iron deficiency on myocytes and the molecular mechanism of muscle atrophy by iron deficiency were evaluated. Our study revealed that the lower iron concentration in injured muscle was associated with the upregulation of ferroportin, an iron exporter that transports iron out of cells. Ferroportin expression was increased by hypoxia-inducible factor 1α (HIF1α), which is activated by muscle injury, and its expression is controlled by HIF1 inhibitor treatment. Iron deprivation caused myocyte loss and a marked depletion of mitochondrial membrane potential leading to muscle atrophy, together with increased levels of myostatin, the upstream regulator of atrogin1 and muscle RING-finger protein-1 (MuRF1). Myostatin expression under iron deficiency was mediated by an orphan nuclear receptor, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome (DAX1).
27
McGrath, Meagan J., Christina A. Mitchell, Imogen D. Coghill, Paul A. Robinson, and Susan Brown. "Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces α5β1-integrin-dependent myocyte elongation." American Journal of Physiology-Cell Physiology 285, no. 6 (December 2003): C1513—C1526. http://dx.doi.org/10.1152/ajpcell.00207.2003.
Full textAbstract:
Skeletal muscle LIM protein 1 (SLIM1/FHL1) contains four and a half LIM domains and is highly expressed in skeletal and cardiac muscle. Elevated SLIM1 mRNA expression has been associated with postnatal skeletal muscle growth and stretch-induced muscle hypertrophy in mice. Conversely, SLIM1 mRNA levels decrease during muscle atrophy. Together, these observations suggest a link between skeletal muscle growth and increased SLIM1 expression. However, the precise function of SLIM1 in skeletal muscle, specifically the role of SLIM1 during skeletal muscle differentiation, is not known. This study investigated the effect of increased SLIM1 expression during skeletal muscle differentiation. Western blot analysis showed an initial decrease followed by an increase in SLIM1 expression during differentiation. Overexpression of SLIM1 in Sol8 or C2C12 skeletal muscle cell lines, at levels observed during hypertrophy, induced distinct effects in differentiating myocytes and undifferentiated reserve cells, which were distinguished by differential staining for two markers of differentiation, MyoD and myogenin. In differentiating skeletal myocytes, SLIM1 overexpression induced hyperelongation, which, by either plating cells on poly-l-lysine or using a series of peptide blockade experiments, was shown to be specifically dependent on ligand binding to the α5β1-integrin, whereas in reserve cells, SLIM1 overexpression induced the formation of multiple cytoplasmic protrusions (branching), which was also integrin mediated. These results suggest that SLIM1 may play an important role during the early stages of skeletal muscle differentiation, specifically in α5β1-integrin-mediated signaling pathways.
28
Kobak, Kamil A. "The influence of iron availability on the structural changes of skeletal muscle cells and cardiac muscle cells." Postępy Polskiej Medycyny i Farmacji 8 (June 9, 2021): 11–16. http://dx.doi.org/10.5604/01.3001.0014.9184.
Full textAbstract:
In the presented study, the influence iron availability on the cell morphology and structure was examined in skeletal myocytes cultured under normoxic and hypoxic conditions. The study showed that iron deficiency in vitro (especially in combination with hypoxia) has a detrimental effect on skeletal myocytes. Cellular disfunction was manifested by atrophic changes in cell morphology, structural remodeling of cells and increased expression of muscle atrophy markers. Interestingly, increased iron availability appeared to have some protective properties in the context of aforementioned changes. Moreover, based on clinical data and recent transgenic models, structural and functional abnormalities in iron-deficient cardiac muscle were described and the potential pathomechanisms behind them have been discussed.
29
Tishevskaya, N. V., E. S. Golovneva, R. V. Gallyamutdinov, A. A. Pozina, and N. M. Gevorkyan. "Xenogeneic lymphocytic RNA stimulates skeletal muscle regeneration." Russian Journal of Transplantology and Artificial Organs 23, no. 3 (September 16, 2021): 134–41. http://dx.doi.org/10.15825/1995-1191-2021-3-134-141.
Full textAbstract:
Objective: to find evidence of the existence of distant lymphocytic RNA control of physiological myogenesis as a way to control the muscle tissue regeneration process.Materials and methods. The study was conducted on male Wistar rats, n=33. In the first part of the experiment, 12 rats were subjected to regular 40-day physical activity (swimming), half of them were intraperitoneally injected 4 times with total RNA isolated from pig spleen lymphocytes at 30 days of age; 6 rats made up the intact control group. In histological preparations of different skeletal muscle groups, the width and cross-sectional area of muscle fibers, the area of nuclei, and the number of myocytes and myosatellite cells were evaluated. In the second part of the experiment, 15 intact rats were injected with the studied xenogeneic RNA and the amounts of ribonucleic acids in peripheral blood lymphocytes, spleen lymphocytes, and skeletal muscles were determined 2 hours and 24 hours after injection.Results. After the 40- day physical activity, the width of the fibers and the area of myocyte nuclei in the skeletal muscles increased; the absolute number of myosatellite cells and the area of their nuclei did not change. After administration of xenogenic RNA in the trained rats, in addition to an increase in the thickness and cross-sectional area of muscle fibers, the absolute number of myosatellite cells in m. biceps femoris, in m. triceps brachii, and in m. pectoralis major increased 1.4-fold, 1.3-fold, and 1.4-fold, respectively; the area of myosatellite nuclei increased on average by 7%. In intact rats, two hours after xenogeneic RNA injection, the amount of RNA in skeletal muscles remained unchanged, it increased by 19% in spleen lymphocytes, and by 16% in peripheral blood lymphocytes. At 24 hours, the RNA amount in the lymphocytes remained significantly higher than the control values, while in the muscle tissue, it didn’t differ from the control.Conclusion. Xenogeneic lymphocytic RNA stimulates physiological myogenesis by activating myosatellite cell proliferation.
30
Jiwlawat, Nunnapas, Eileen Lynch, Jeremy Jeffrey, Jonathan M. Van Dyke, and Masatoshi Suzuki. "Current Progress and Challenges for Skeletal Muscle Differentiation from Human Pluripotent Stem Cells Using Transgene-Free Approaches." Stem Cells International 2018 (2018): 1–18. http://dx.doi.org/10.1155/2018/6241681.
Full textAbstract:
Neuromuscular diseases are caused by functional defects of skeletal muscles, directly via muscle pathology or indirectly via disruption of the nervous system. Extensive studies have been performed to improve the outcomes of therapies; however, effective treatment strategies have not been fully established for any major neuromuscular disease. Human pluripotent stem cells have a great capacity to differentiate into myogenic progenitors and skeletal myocytes for use in treating and modeling neuromuscular diseases. Recent advances have allowed the creation of patient-derived stem cells, which can be used as a unique platform for comprehensive study of disease mechanisms, in vitro drug screening, and potential new cell-based therapies. In the last decade, a number of methods have been developed to derive skeletal muscle cells from human pluripotent stem cells. By controlling the process of myogenesis using transcription factors and signaling molecules, human pluripotent stem cells can be directed to differentiate into cell types observed during muscle development. In this review, we highlight signaling pathways relevant to the formation of muscle tissue during embryonic development. We then summarize current methods to differentiate human pluripotent stem cells toward the myogenic lineage, specifically focusing on transgene-free approaches. Lastly, we discuss existing challenges for deriving skeletal myocytes and myogenic progenitors from human pluripotent stem cells.
31
Iida, H., T. Hatae, and Y. Shibata. "Immunocytochemical localization of 67 KD Ca2+ binding protein (p67) in ventricular, skeletal, and smooth muscle cells." Journal of Histochemistry & Cytochemistry 40, no. 12 (December 1992): 1899–907. http://dx.doi.org/10.1177/40.12.1453007.
Full textAbstract:
By using immunocytochemical techniques, we examined the localization of a 67 kDa Ca2+ binding protein (p67) and calpactin I heavy chain (p36) in ventricular myocytes, skeletal myocytes, and intestinal smooth muscle cells. Immunofluorescence microscopy revealed that the p67 was expressed in all these muscle cells, whereas anti-p36 antibody stained cells in connective tissues but failed to stain these muscle cells. Immunogold electron microscopy was carried out to examine the subcellular localization of the p67 in muscle cells. The results showed that the p67 was exclusively confined to the plasma membrane of muscle cells and the presumptive transverse tubules of the striated myocytes. Immunoblot analysis with anti-p67 antibody showed that the p67 was indeed a constitutive protein of the sarcolemma isolated from rat hearts. These results indicate that the p67 is a sarcolemma-associated Ca2+ binding protein expressed in both striated myocytes and intestinal smooth muscle cells.
32
Cho, Eun-Jeong, Youngju Choi, Jiyeon Kim, Jun Hyun Bae, Jinkyung Cho, Dong-Ho Park, Ju-Hee Kang, et al. "Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle." International Neurourology Journal 25, Suppl 2 (November 30, 2021): S47–54. http://dx.doi.org/10.5213/inj.2142334.167.
Full textAbstract:
Purpose: The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated.Methods: Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis.Results: The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group.Conclusions: Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle.
33
Suryadevara, Vidyani, and Monte S. Willis. "Walk the Line: The Role of Ubiquitin in Regulating Transcription in Myocytes." Physiology 34, no. 5 (September 1, 2019): 327–40. http://dx.doi.org/10.1152/physiol.00055.2018.
Full textAbstract:
The ubiquitin-proteasome offers novel targets for potential therapies with their specific activities and tissue localization. Recently, the expansion of our understanding of how ubiquitin ligases (E3s) specifically regulate transcription has demonstrated their roles in skeletal muscle, complementing their roles in protein quality control and protein degradation. This review focuses on skeletal muscle E3s that regulate transcription factors critical to myogenesis and the maintenance of skeletal muscle wasting diseases.
34
Nedachi, Taku, Hiroyasu Hatakeyama, Tatsuyoshi Kono, Masaaki Sato, and Makoto Kanzaki. "Characterization of contraction-inducible CXC chemokines and their roles in C2C12 myocytes." American Journal of Physiology-Endocrinology and Metabolism 297, no. 4 (October 2009): E866—E878. http://dx.doi.org/10.1152/ajpendo.00104.2009.
Full textAbstract:
Physical exercise triggers the release of several cytokines/chemokines from working skeletal muscles, but the underlying mechanism(s) by which skeletal muscles decipher and respond to highly complex contractile stimuli remains largely unknown. In an effort to investigate the regulatory mechanisms of the expressions of two contraction-inducible CXC chemokines, CXCL1/KC and CXCL5/LIX, in contracting skeletal muscle cells, we took advantage of our in vitro exercise model using highly developed contractile C2C12 myotubes, which acquire properties similar to those of in vivo skeletal muscle via manipulation of Ca2+ transients with electric pulse stimulation (EPS). Production of these CXC chemokines was immediately augmented by EPS-evoked contractile activity in a manner dependent on the activities of JNK and NF-κB, but not p38, ERK1/2, or calcineurin. Intriguingly, exposure of myotubes to cyclic mechanical stretch also induced expression of these CXC chemokines; however, a much longer period of stimulation (∼12 h) was required, despite rapid JNK phosphorylation. We also demonstrate herein that CXCL1/KC and CXCL5/LIX have the ability to raise intracellular Ca2+ concentrations via CXCR2-mediated activation of pertussis toxin-sensitive Gαi proteins in C2C12 myoblasts, an action at least partially responsible for their migration and differentiation. Although we revealed a possible negative feedback regulation of their own production in response to the contractile activity in differentiated myotubes, exogenous administration of these CXC chemokines did not acutely influence either insulin-induced Akt phosphorylation or GLUT4 translocation in C2C12 myotubes. Taken together, these data shed light on the fundamental characteristics of contraction-inducible CXC chemokine production and their potential roles in skeletal muscle cells.
35
Kindig, Casey A., Brandon Walsh, Richard A. Howlett, Creed M. Stary, and Michael C. Hogan. "Relationship between intracellular Po2 recovery kinetics and fatigability in isolated single frog myocytes." Journal of Applied Physiology 98, no. 6 (June 2005): 2316–19. http://dx.doi.org/10.1152/japplphysiol.00355.2004.
Full textAbstract:
In single frog skeletal myocytes, a linear relationship exists between “fatigability” and oxidative capacity. The purpose of this investigation was to study the relationship between the intracellular Po2 (PiO2) offset kinetics and fatigability in single Xenopus laevis myocytes to test the hypothesis that PiO2 offset kinetics would be related linearly with myocyte fatigability and, by inference, oxidative capacity. Individual myocytes ( n = 30) isolated from lumbrical muscle were subjected to a 2-min bout of isometric peak tetanic contractions at either 0.25- or 0.33-Hz frequency while PiO2 was measured continuously via phosphorescence quenching techniques. The mean response time (MRT; time to 63% of the overall response) for PiO2 recovery from contracting values to resting baseline was calculated. After the initial square-wave constant-frequency contraction trial, each cell performed an incremental contraction protocol [i.e., frequency increase every 2 min from 0.167, 0.25, 0.33, 0.5, 1.0, and 2.0 Hz until peak tension fell below 50% of initial values (TTF)]. TTF values ranged from 3.39 to 10.04 min for the myocytes. The PiO2 recovery MRT ranged from 26 to 146 s. A significant ( P < 0.05), negative relationship (MRT = −12.68TTF + 168.3, r2 = 0.605) between TTF and PiO2 recovery MRT existed. These data demonstrate a significant correlation between fatigability and oxidative phosphorylation recovery kinetics consistent with the notion that oxidative capacity determines, in part, the speed with which skeletal muscle can recover energetically to alterations in metabolic demand.
36
Novitch, B. G., G. J. Mulligan, T. Jacks, and A. B. Lassar. "Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle." Journal of Cell Biology 135, no. 2 (October 15, 1996): 441–56. http://dx.doi.org/10.1083/jcb.135.2.441.
Full textAbstract:
Viral oncoproteins that inactivate the retinoblastoma tumor suppressor protein (pRb) family both block skeletal muscle differentiation and promote cell cycle progression. To clarify the dependence of terminal differentiation on the presence of the different pRb-related proteins, we have studied myogenesis using isogenic primary fibroblasts derived from mouse embryos individually deficient for pRb, p107, or p130. When ectopically expressed in fibroblasts lacking pRb, MyoD induces an aberrant skeletal muscle differentiation program characterized by normal expression of early differentiation markers such as myogenin and p21, but attenuated expression of late differentiation markers such as myosin heavy chain (MHC). Similar defects in MHC expression were not observed in cells lacking either p107 or p130, indicating that the defect is specific to the loss of pRb. In contrast to wild-type, p107-deficient, or p130-deficient differentiated myocytes that are permanently withdrawn from the cell cycle, differentiated myocytes lacking pRb accumulate in S and G2 phases and express extremely high levels of cyclins A and B, cyclin-dependent kinase (Cdk2), and Cdc2, but fail to readily proceed to mitosis. Administration of caffeine, an agent that removes inhibitory phosphorylations on inactive Cdc2/cyclin B complexes, specifically induced mitotic catastrophe in pRb-deficient myocytes, consistent with the observation that the majority of pRb-deficient myocytes arrest in S and G2. Together, these findings indicate that pRb is required for the expression of late skeletal muscle differentiation markers and for the inhibition of DNA synthesis, but that a pRb-independent mechanism restricts entry of differentiated myocytes into mitosis.
37
Metzger, J. M. "pH dependence of myosin binding-induced activation of the thin filament in cardiac myocytes and skeletal fibers." American Journal of Physiology-Heart and Circulatory Physiology 270, no. 3 (March 1, 1996): H1008—H1014. http://dx.doi.org/10.1152/ajpheart.1996.270.3.h1008.
Full textAbstract:
The pH dependence of myosin binding-induced thin filament activation was determined in permeabilized cardiac myocytes and slow- and fast-twitch single skeletal muscle fibers by experimental lowering of [MgATP] in the Ca(2+)-free solutions bathing the permeabilized preparations. As the pS (where S is [MgATP] and pS is -log[MgATP]) was increased from 3.0 to 8.0, isometric tension increased to a peak value in the pS range of 4.9-5.3. At pH 7.00, the transition from the relaxed to the activated rigor state was steep in cardiac myocytes [Hill value (nH) = 21.2 +/- 3.1 (SE)] and due to the apparent effect of strongly bound cross bridges to cooperatively activate the thin filament in the absence of added Ca2+. At pH 6.20, the steepness of the tension-pS relationship was markedly reduced (nH = 6.1 +/- 1.0) and the midpoint of the relationship (pS50) was shifted to higher pS values in cardiac myocytes. In comparison, reduced pH had no effect on the steepness or position of the tension-pS relationship in single slow- or fast-twitch skeletal muscle fibers. These findings suggest that myosin binding-induced activation of the thin filament is pH dependent in cardiac myocytes but not in skeletal muscle fibers under these experimental conditions in which Ca2+ is absent.
38
Reyes-Juárez, José Luis, Raúl Juárez-Rubí, Gabriela Rodríguez, and Angel Zarain-Herzberg. "Transcriptional Analysis of the Human Cardiac Calsequestrin Gene in Cardiac and Skeletal Myocytes." Journal of Biological Chemistry 282, no. 49 (October 15, 2007): 35554–63. http://dx.doi.org/10.1074/jbc.m707788200.
Full textAbstract:
Calsequestrin is the main calcium-binding protein inside the sarcoplasmic reticulum of striated muscle. In mammals, the cardiac calsequestrin gene (casq2) mainly expresses in cardiac muscle and to a minor extent in slow-twitch skeletal muscle and it is not expressed in non-muscle tissues. This work is the first study on the transcriptional regulation of the casq2 gene in cardiac and skeletal muscle cells. The sequence of the casq2 genes proximal promoter (180 bp) of mammals and avians is highly conserved and contains one TATA box, one CArG box, one E-box, and one myocyte enhancer factor 2 (MEF-2) site. We cloned the human casq2 gene 5′-regulatory region into a luciferase reporter expression vector. By functional assays we showed that a construct containing the first 288 bp of promoter was up-regulated during myogenic differentiation of Sol8 cells and had higher transcriptional activity compared with longer constructs. In neonatal rat cardiac myocytes, the larger construct containing 3.2 kb showed the highest transcriptional activity, demonstrating that the first 288 bp are sufficient to confer muscle specificity, whereas distal sequences may act as a cardiac-specific enhancer. Electrophoretic mobility shift assay studies demonstrated that the proximal MEF-2 and CArG box sequences were capable of binding MEF-2 and serum response factor, respectively, whereas the E-box did not show binding properties. Functional studies demonstrated that site-directed mutagenesis of the proximal MEF-2 and CArG box sites significantly decreased the transcription of the gene in cardiac and skeletal muscle cells, indicating that they are important to drive cardiac and skeletal muscle-specific transcription of the casq2 gene.
39
Parmacek, M. S., A. J. Vora, T. Shen, E. Barr, F. Jung, and J. M. Leiden. "Identification and characterization of a cardiac-specific transcriptional regulatory element in the slow/cardiac troponin C gene." Molecular and Cellular Biology 12, no. 5 (May 1992): 1967–76. http://dx.doi.org/10.1128/mcb.12.5.1967-1976.1992.
Full textAbstract:
The slow/cardiac troponin C (cTnC) gene has been used as a model system for defining the molecular mechanisms that regulate cardiac and skeletal muscle-specific gene expression during mammalian development. cTnC is expressed continuously in both embryonic and adult cardiac myocytes but is expressed only transiently in embryonic fast skeletal myotubes. We have reported previously that cTnC gene expression in skeletal myotubes is controlled by a developmentally regulated, skeletal muscle-specific transcriptional enhancer located within the first intron of the gene (bp 997 to 1141). In this report, we show that cTnC gene expression in cardiac myocytes both in vitro and in vivo is regulated by a distinct and independent transcriptional promoter and enhancer located within the immediate 5' flanking region of the gene (bp -124 to +32). DNase I footprint and electrophoretic mobility shift assay analyses demonstrated that this cardiac-specific promoter/enhancer contains five nuclear protein binding sites (designated CEF1, CEF-2, and CPF1-3), four of which bind novel cardiac-specific nuclear protein complexes. Functional analysis of the cardiac-specific cTnC enhancer revealed that mutation of either the CEF-1 or CEF-2 nuclear protein binding site abolished the activity of the cTnC enhancer in cardiac myocytes. Taken together, these results define a novel mechanism for developmentally regulating a single gene in multiple muscle cell lineages. In addition, they identify previously undefined cardiac-specific transcriptional regulatory motifs and trans-acting factors. Finally, they demonstrate distinct transcriptional regulatory pathways in cardiac and skeletal muscle.
40
Parmacek, M. S., A. J. Vora, T. Shen, E. Barr, F. Jung, and J. M. Leiden. "Identification and characterization of a cardiac-specific transcriptional regulatory element in the slow/cardiac troponin C gene." Molecular and Cellular Biology 12, no. 5 (May 1992): 1967–76. http://dx.doi.org/10.1128/mcb.12.5.1967.
Full textAbstract:
The slow/cardiac troponin C (cTnC) gene has been used as a model system for defining the molecular mechanisms that regulate cardiac and skeletal muscle-specific gene expression during mammalian development. cTnC is expressed continuously in both embryonic and adult cardiac myocytes but is expressed only transiently in embryonic fast skeletal myotubes. We have reported previously that cTnC gene expression in skeletal myotubes is controlled by a developmentally regulated, skeletal muscle-specific transcriptional enhancer located within the first intron of the gene (bp 997 to 1141). In this report, we show that cTnC gene expression in cardiac myocytes both in vitro and in vivo is regulated by a distinct and independent transcriptional promoter and enhancer located within the immediate 5' flanking region of the gene (bp -124 to +32). DNase I footprint and electrophoretic mobility shift assay analyses demonstrated that this cardiac-specific promoter/enhancer contains five nuclear protein binding sites (designated CEF1, CEF-2, and CPF1-3), four of which bind novel cardiac-specific nuclear protein complexes. Functional analysis of the cardiac-specific cTnC enhancer revealed that mutation of either the CEF-1 or CEF-2 nuclear protein binding site abolished the activity of the cTnC enhancer in cardiac myocytes. Taken together, these results define a novel mechanism for developmentally regulating a single gene in multiple muscle cell lineages. In addition, they identify previously undefined cardiac-specific transcriptional regulatory motifs and trans-acting factors. Finally, they demonstrate distinct transcriptional regulatory pathways in cardiac and skeletal muscle.
41
Hutchinson, Amber, Danyelle Liddle, Rufaida Ansari, and Lindsay Robinson. "Dietary n-3 vs n-6 PUFA Differentially Modulate Macrophage-Myocyte Inflammatory Cross-Talk." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1644. http://dx.doi.org/10.1093/cdn/nzaa063_042.
Full textAbstract:
Abstract Objectives Skeletal muscle is the primary site for insulin-stimulated glucose uptake. In obesity, increased circulating inflammatory cytokines interfere with skeletal muscle insulin signaling, leading to local and whole-body insulin resistance (IR). Moreover, obese skeletal muscle is characterized by accumulation of infiltrated M1 macrophages and ensuing macrophage-myocyte paracrine interactions (cross-talk) contribute to local inflammation and IR. Such macrophage-myocyte inflammatory cross-talk provides a potential intervention target for anti-inflammatory nutrients, including dietary long-chain n-3 polyunsaturated fatty acids (PUFA). Methods Using a co-culture model designed to mimic the degree of CD11b+ cell accumulation in obese skeletal muscle (40% of immune cells), differentiated L6 myocytes were co-cultured with purified splenic CD11b+ cells from male Sprague Dawley rats (7-wk old) consuming one of three isocaloric diets: i) high-fat (HF; 54% kcal lard, 6% kcal soybean oil), ii) high-fat with n-3 PUFA (HFn-3; 39% kcal lard + 15% kcal menhaden oil + 6% kcal soybean oil) or iii) high-fat with n-6 PUFA (HFn-6; 45% kcal lard + 15% kcal soybean oil) for 2, 8 or 12-wk (n = 8–12/diet). Co-cultures were stimulated for 24 h with lipopolysaccharide (LPS, 10 ng/mL) to mimic in vivo obese endotoxin levels. CD11b+ cells were also cultured alone for 24 h in conditioned media collected from L6 myocytes stimulated with LPS for 24 h (LCM). Results In co-cultures, HFn-6 increased mRNA expression of inflammatory markers compared to HF and HFn-3 at 8- (iNos; P ≤ 0.05) and 12-wk (Tnf-α, Il-6, Il-1β; P ≤ 0.05). Similarly, at 8-wk CD11b+ cells from HFn-6 rats that were treated with LCM, had increased mRNA expression of inflammatory cytokines (Tnf-α, Il-1β) and M1 polarization markers (iNos, Cd86) compared to both HF and HFn-3, and the same effects were seen with Il-6 and Il-1β at 12-wk (P ≤ 0.05). Lastly, HFn-3 reduced mRNA expression of Tnf-α compared to HF at 12-wk (P ≤ 0.05). Conclusions Together, these data suggest that n-6 PUFA support macrophage-myocyte inflammatory cross-talk, in part by promoting M1 macrophage polarization. Further, these data provide mechanistic insight into the benefits of n-3 vs n-6 PUFA inclusion in a high-fat diet in mitigating skeletal muscle inflammation in obesity. Funding Sources Natural Sciences and Engineering Research Council (NSERC) of Canada.
42
Huang, T. E. "EFFECTS OF AZT ON CULTURED HUMAN SKELETAL MUSCLE MYOCYTES." Journal of Neuropathology and Experimental Neurology 52, no. 3 (May 1993): 299. http://dx.doi.org/10.1097/00005072-199305000-00155.
Full text
43
Donoviel, D. B., M. A. Shield, J. N. Buskin, H. S. Haugen, C. H. Clegg, and S. D. Hauschka. "Analysis of muscle creatine kinase gene regulatory elements in skeletal and cardiac muscles of transgenic mice." Molecular and Cellular Biology 16, no. 4 (April 1996): 1649–58. http://dx.doi.org/10.1128/mcb.16.4.1649.
Full textAbstract:
Regulatory regions of the mouse muscle creatine kinase (MCK) gene, previously discovered by analysis in cultured muscle cells, were analyzed in transgenic mice. The 206-bp MCK enhancer at nt-1256 was required for high-level expression of MCK-chloramphenicol acetyltransferase fusion genes in skeletal and cardiac muscle; however, unlike its behavior in cell culture, inclusion of the 1-kb region of DNA between the enhancer and the basal promoter produced a 100-fold increase in skeletal muscle activity. Analysis of enhancer control elements also indicated major differences between their properties in transgenic muscles and in cultured muscle cells. Transgenes in which the enhancer right E box or CArG element were mutated exhibited expression levels that were indistinguishable from the wild-type transgene. Mutation of three conserved E boxes in the MCK 1,256-bp 5' region also had no effect on transgene expression in thigh skeletal muscle expression. All these mutations significantly reduced activity in cultured skeletal myocytes. However, the enhancer AT-rich element at nt - 1195 was critical for expression in transgenic skeletal muscle. Mutation of this site reduced skeletal muscle expression to the same level as transgenes lacking the 206-bp enhancer, although mutation of the AT-rich site did not affect cardiac muscle expression. These results demonstrate clear differences between the activity of MCK regulatory regions in cultured muscles cells and in whole adult transgenic muscle. This suggests that there are alternative mechanism of regulating the MCK gene in skeletal and cardiac muscle under different physiological states.
44
Kronebusch, P. J., and S. J. Singer. "The microtubule-organizing complex and the Golgi apparatus are co-localized around the entire nuclear envelope of interphase cardiac myocytes." Journal of Cell Science 88, no. 1 (August 1, 1987): 25–34. http://dx.doi.org/10.1242/jcs.88.1.25.
Full textAbstract:
In most animal cells, the microtubule-organizing centre (MTOC) and the Golgi apparatus (GA) are co-localized on one side of the nucleus, an arrangement that allows these cells to acquire a functional polarity. An exception has been reported in the skeletal muscle myotube, where the MTOC and GA exhibit a circumnuclear distribution. We wished to determine if this unusual distribution of the MTOC and GA was peculiar to syncytial myotubes or reflected a pattern found in muscle cells generally. Immunofluorescence microscopic studies of cultured chicken skeletal muscle, cardiac muscle and gizzard smooth muscle cells were carried out using preimmune sera that recognized the pericentriolar material, anti-tubulin antibodies to label the MTOC, and fluorescent wheat-germ agglutinin to label the GA. These studies have shown that cardiac myocytes possess a circumnuclear distribution of their MTOC and GA as do skeletal myotubes, but smooth muscle cells exhibit the centrosomal MTOC and GA distribution found in most other cells. The circumnuclear MTOC/GA distribution therefore is associated with striated muscle cells. We also found that as embryonic cardiac myocytes pass through the cell cycle the microtubule-organizing activity in these cells switches from a circumnuclear distribution in interphase to the conventional centrosomal location during mitosis. Thus, cardiac myocytes provide a rare example of mononucleated animal cells that do not display a centrosomal MTOC or a polarized GA, and also reveal a system in which the MTOC structure can be reversibly altered in a cell cycle-dependent manner.
45
Michele, Daniel E., Pierre Coutu, and Joseph M. Metzger. "Divergent abnormal muscle relaxation by hypertrophic cardiomyopathy and nemaline myopathy mutant tropomyosins." Physiological Genomics 9, no. 2 (May 10, 2002): 103–11. http://dx.doi.org/10.1152/physiolgenomics.00099.2001.
Full textAbstract:
Mutations in tropomyosin (Tm) have been linked to distinct inherited diseases of cardiac and skeletal muscle, hypertrophic cardiomyopathy (HCM), and nemaline myopathy (NM). How HCM and NM mutations in nearly identical Tm proteins produce the vastly divergent clinical phenotypes of heightened, prolonged cardiac muscle contraction in HCM and skeletal muscle weakness in NM is currently unknown. We report here a direct comparison of the effects of HCM (A63V) and NM (M9R) mutant Tm on membrane-intact myocyte contractile function as assessed by adenoviral gene transfer to fully differentiated cardiac muscle cells. Wild-type, and mutant HCM, and mutant NM proteins were expressed at similar levels in myocytes and incorporated into sarcomeres. Interestingly, HCM mutant Tm produced significantly longer contractions by slowing relaxation, whereas NM mutant Tm produced the opposite effect of accelerated muscle relaxation. We propose slowed relaxation caused by HCM mutant Tm can directly contribute to diastolic dysfunction seen in HCM even without secondary cardiac remodeling. Conversely, hastening of relaxation by NM mutant Tm may shift the force-frequency relationship in skeletal muscle and contribute to muscle weakness seen in NM. Together, these results implicate divergent, abnormal “turning off” of muscle contraction as a cellular basis for the differential pathogenesis of mutant Tm-associated HCM and NM.
46
Vasyukova, O. V., Yu V. Kasyanova, P. L. Okorokov, and O. B. Bezlepkina. "Myokines and adipomyokines: inflammatory mediators or unique molecules of targeted therapy for obesity?" Problems of Endocrinology 67, no. 4 (September 16, 2021): 36–45. http://dx.doi.org/10.14341/probl12779.
Full textAbstract:
Skeletal muscles make up about 25% of the total mass in children and more than 40% in adults. Studies of the last twenty years have shown that along with the main functions, muscle tissue has hormonal activity. It was found that myocytes are able to release signaling molecules-myokines. They act auto-and paracrine within the muscle, and at a high level-through the systemic circulation, carrying out interactions between skeletal muscles and various organs and tissues, such as the liver, bone and adipose tissue, the brain. It is proved that the key factor in the expression of myokines is physical activity, and their level largely depends on physical fitness, the amount of skeletal muscle mass and its composition (the ratio of fast and slow fibers), on the intensity and duration of physical activity. Myokines have a wide range of physiological effects: myostatin suppresses the growth and differentiation of muscle tissue, and decorin, acting as its antagonist, promotes muscle hypertrophy. Interleukin 6 provides an energy substrate for contracting muscle fibers, fibroblast growth factor 21 activates the mechanisms of energy production during fasting and improves tissue sensitivity to insulin; irisin stimulates thermogenesis, glucose uptake by myocytes, and also contributes to an increase in bone mineral density. The study of myokines is one of the key links in understanding the mechanisms underlying obesity and metabolic complications, the consequences of a sedentary lifestyle, as well as the implementation of the action of physical activity. Taking into account the physiological effects of myokines in the body, in the future they can become therapeutic targets for the treatment of these conditions.
47
Jortay, Julie, Maximin Senou, Aurélie Delaigle, Laurence Noel, Tohru Funahashi, Norikazu Maeda, Marie C. Many, and Sonia M. Brichard. "Local Induction of Adiponectin Reduces Lipopolysaccharide-Triggered Skeletal Muscle Damage." Endocrinology 151, no. 10 (August 11, 2010): 4840–51. http://dx.doi.org/10.1210/en.2009-1462.
Full textAbstract:
Adiponectin (ApN) exhibits metabolic and antiinflammatory properties. This hormone is exclusively secreted by adipocytes under normal conditions. We have shown that ApN was induced in tibialis anterior muscle of mice injected with lipopolysaccharide (LPS) and in C2C12 myotubes cultured with proinflammatory cytokines. We hypothesized that muscle ApN could be a local protective mechanism to counteract excessive inflammatory reaction and oxidative damage. To test this paradigm, we examined whether muscles of ApN-knockout (KO) mice exhibit a higher degree of oxidative stress and apoptosis than wild-type mice when challenged by ip LPS and whether these abnormalities may be corrected by local administration of ApN. Eventually we investigated the effects of ApN in vitro. When compared with wild-type mice, ApN-KO mice exhibited myocyte degenerescence, especially after LPS. Myocytes of ApN-KO mice also displayed much stronger immunolabeling for markers of oxidative stress (peroxiredoxin-3/5 and heme oxygenase-1) as well as for a lipid peroxidation product (hydroxynonenal). Expression of TNF-α, caspase-6, a marker of apoptosis, and nuclear factor-κB was enhanced as well. Eventually muscle electrotransfer of the ApN gene, which did not induce any rise of systemic ApN, corrected all these abnormalities in LPS-injected ApN-KO mice. Likewise, ApN attenuated LPS-induced production of proinflammatory cytokines and activation of nuclear factor-κB in C2C12 cells. Thus, induction of ApN into skeletal muscle in response to an inflammatory aggression appears to be a crucial mechanism to counteract in an autocrine or paracrine fashion excessive inflammatory damage, oxidative stress, and subsequent apoptosis.
48
Gallyamutdinov, R. V., E. S. Golovneva, Zh A. Revel-Muroz, and I. V. Elovsky. "Infrared laser exposure in combination with branchedchain amino acid stimulates physiological adaptation of skeletal muscles." Laser Medicine 25, no. 3 (January 22, 2022): 40–46. http://dx.doi.org/10.37895/2071-8004-2021-25-3-40-46.
Full textAbstract:
Laser exposure stimulates cell proliferation and tissue repair. Branched-chain amino acids (BCAA) are widely used in sports medicine as a stimulator of anabolic processes. However, there is no evidence of the effect of combined laser and BCAA application on skeletal muscle morphometric characteristics during exercise in the training process.Purpose: to study the effect of infrared laser exposure in combination with amino acid at myosatellitocytes and skeletal muscle myocytes during swimming training.Material and methods. The experiment was conducted on 30 Wistar rats: Group 1 – intact, Group 2 – dynamic control (trainings with endurance swimming), Group 3 – trainings and BCAA, Group 4 – trainings and laser exposure at hip muscles (970 nm, 1 W, 60 s), Group 5 – combined exposure to laser and BCAA. Trainings were three times a week for 6 weeks; laser session was after each training. Samples of the bipedal thigh muscle were fixed with formalin; histological sections were stained with hematoxylin-eosin. The morphometric analysis of the digital image of objects with statistical processing by Mann – Whitney method was made.Results. Laser exposure combined with BCAA during trainings increased the nuclei area and the number of myosatellites and myocytes; it also enlarged the cross section of muscle fibers which was more pronounced if to compare with isolated laser irradiation of the muscle or BCAA.Conclusions. Infrared laser exposure in combination with branched-chain amino acids effectively stimulates regeneration due to hyperplasia and hypertrophy of skeletal muscular tissue, thus providing physiological adaptation in the training process.
49
Handayaningsih, Anastasia-Evi, Genzo Iguchi, Hidenori Fukuoka, Hitoshi Nishizawa, Michiko Takahashi, Masaaki Yamamoto, Elizabeth-Henny Herningtyas, et al. "Reactive Oxygen Species Play an Essential Role in IGF-I Signaling and IGF-I-Induced Myocyte Hypertrophy in C2C12 Myocytes." Endocrinology 152, no. 3 (March 1, 2011): 912–21. http://dx.doi.org/10.1210/en.2010-0981.
Full textAbstract:
IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. Reactive oxygen species (ROS) modulate the signaling of various growth factors via redox regulation. However, the role of ROS in IGF-I signaling is not fully understood. In this study, we investigated whether ROS regulate the signaling and biological action of IGF-I in C2C12 myocytes. We found that IGF-I induces ROS in C2C12 myocytes. While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. Importantly, antioxidant treatments inhibited IGF-I-induced myocyte hypertrophy, demonstrating that ROS are necessary for IGF-I-induced myocyte hypertrophy in vitro. These results indicate that ROS play an essential role in the signaling and biological action of IGF-I in C2C12 myocytes.
50
Powers, Scott K., Erica Goldstein, Matthew Schrager, and Li Li Ji. "Exercise Training and Skeletal Muscle Antioxidant Enzymes: An Update." Antioxidants 12, no. 1 (December 25, 2022): 39. http://dx.doi.org/10.3390/antiox12010039.
Full textAbstract:
The pivotal observation that muscular exercise is associated with oxidative stress in humans was first reported over 45 years ago. Soon after this landmark finding, it was discovered that contracting skeletal muscles produce oxygen radicals and other reactive species capable of oxidizing cellular biomolecules. Importantly, the failure to eliminate these oxidant molecules during exercise results in oxidation of cellular proteins and lipids. Fortuitously, muscle fibers and other cells contain endogenous antioxidant enzymes capable of eliminating oxidants. Moreover, it is now established that several modes of exercise training (e.g., resistance exercise and endurance exercise) increase the expression of numerous antioxidant enzymes that protect myocytes against exercise-induced oxidative damage. This review concisely summarizes the impact of endurance, high-intensity interval, and resistance exercise training on the activities of enzymatic antioxidants within skeletal muscles in humans and other mammals. We also discuss the evidence that exercise-induced up-regulation of cellular antioxidants reduces contraction-induced oxidative damage in skeletal muscles and has the potential to delay muscle fatigue and improve exercise performance. Finally, in hopes of stimulating further research, we also discuss gaps in our knowledge of exercise-induced changes in muscle antioxidant capacity.