Journal articles on the topic 'Myogenic'
To see the other types of publications on this topic, follow the link: Myogenic.
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 'Myogenic.'
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
Cheng, T. C., T. A. Hanley, J. Mudd, J. P. Merlie, and E. N. Olson. "Mapping of myogenin transcription during embryogenesis using transgenes linked to the myogenin control region." Journal of Cell Biology 119, no. 6 (December 15, 1992): 1649–56. http://dx.doi.org/10.1083/jcb.119.6.1649.
Full textAbstract:
During vertebrate embryogenesis, the muscle-specific helix-loop-helix protein myogenin is expressed in muscle cell precursors in the developing somite myotome and limb bud before muscle fiber formation and is further upregulated during myogenesis. We show that cis-acting DNA sequences within the 5' flanking region of the mouse myogenin gene are sufficient to direct appropriate temporal, spatial, and tissue-specific transcription of myogenin during mouse embryogenesis. Myogenin-lacZ transgenes trace the fate of embryonic cells that activate myogenin transcription and suggest that myogenic precursor cells that migrate from the somite myotome to the limb bud are committed to a myogenic fate in the absence of myogenin transcription. Activation of a myogenin-lacZ transgene can occur in limb bud explants in culture, indicating that signals required for activation of myogenin transcription are intrinsic to the limb bud and independent of other parts of the embryo. These results reveal multiple populations of myogenic precursor cells during development and suggest the existence of regulators other than myogenic helix-loop-helix proteins that maintain cells in the early limb bud in the myogenic lineage.
2
Higashioka, Koki, Noriko Koizumi, Hidetoshi Sakurai, Chie Sotozono, and Takahiko Sato. "Myogenic Differentiation from MYOGENIN-Mutated Human iPS Cells by CRISPR/Cas9." Stem Cells International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/9210494.
Full textAbstract:
It is well known that myogenic regulatory factors encoded by the Myod1 family of genes have pivotal roles in myogenesis, with partially overlapping functions, as demonstrated for the mouse embryo. Myogenin-mutant mice, however, exhibit severe myogenic defects without compensation by other myogenic factors. MYOGENIN might be expected to have an analogous function in human myogenic cells. To verify this hypothesis, we generated MYOGENIN-mutated human iPS cells by using CRISPR/Cas9 genome-editing technology. Our results suggest that MYOD1-independent or MYOD1-dependent mechanisms can compensate for the loss of MYOGENIN and that these mechanisms are likely to be crucial for regulating skeletal muscle differentiation and formation.
3
Wang, Y., and R. Jaenisch. "Myogenin can substitute for Myf5 in promoting myogenesis but less efficiently." Development 124, no. 13 (July 1, 1997): 2507–13. http://dx.doi.org/10.1242/dev.124.13.2507.
Full textAbstract:
The myogenic basic Helix-Loop-Helix transcription factors, including Myf5, MyoD, myogenin (myg) and MRF4, play important roles in skeletal muscle development. The phenotypes of mutant mice deficient in either gene are different, suggesting that each gene may have a unique function in vivo. We previously showed that targeting myogenin into the Myf5 locus (Myf5(myg-ki)) rescued the rib cage truncation in the Myf5-null mutant, hence demonstrating functional redundancy between Myf5 and myogenin in skeletal morphogenesis. Here we present the results of crossing myogenin knock-in (myg-ki) mice with either MyoD-null or myogenin-null mutants. The Myf5(myg-ki) allele rescued early myogenesis, but Myf5(myg-ki/myg-ki);MyoD(−/−) mutant mice died immediately after birth owing to reduced muscle formation. Therefore, myogenin, expressed from the Myf5 locus, is not able to completely replace the function of Myf5 in muscle development although it is capable of determining and/or maintaining myogenic lineage. Myf5(myg-ki/myg-ki);myg(−/−) mutant mice displayed the same phenotype as myg(−/−) mutants. This indicates that the earlier expression of myogenin cannot promote myogenic terminal differentiation, which is normally initiated by the endogenous myogenin. Thus, our results are consistent with the notion that Myf5 and myogenin are functionally interchangeable in determining myogenic lineage and assuring normal rib formation. Our experiment revealed, however, that some aspects of myogenesis may be unique to a given myogenic factor and are due to either different regulatory sequences that control their temporal and spatial expression or different functional protein domains.
4
Rawls, A., M. R. Valdez, W. Zhang, J. Richardson, W. H. Klein, and E. N. Olson. "Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice." Development 125, no. 13 (July 1, 1998): 2349–58. http://dx.doi.org/10.1242/dev.125.13.2349.
Full textAbstract:
The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 - exhibit distinct, but overlapping expression patterns during development of the skeletal muscle lineage and loss-of-function mutations in these genes result in different effects on muscle development. MyoD and Myf5 have been shown to act early in the myogenic lineage to establish myoblast identity, whereas myogenin acts later to control myoblast differentiation. In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal muscle, but they upregulate myogenin expression, which could potentially compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null mutations were combined suggested that these genes do not share overlapping myogenic functions in vivo. To determine whether the functions of MRF4 might overlap with those of myogenin or MyoD, we generated double mutant mice lacking MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a comparable number of residual muscle fibers to mice lacking myogenin alone and myoblasts from those double mutant mice formed differentiated multinucleated myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas mice lacking either MRF4 or MyoD were viable and did not show defects in muscle development, MRF4/MyoD double mutants displayed a severe muscle deficiency similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double mutants, indicating that myogenin is insufficient to support normal myogenesis in vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in the muscle differentiation pathway and suggest that a threshold level of myogenic bHLH factors is required to activate muscle structural genes, with this level normally being achieved by combinations of multiple myogenic bHLH factors.
5
Gómez, JoséA, Mahul B. Amin, Jae Y. Ro, Michael D. Linden, Min W. Lee, and Richard J. Zarbo. "Immunohistochemical Profile of Myogenin and MyoD1 Does Not Support Skeletal Muscle Lineage in Alveolar Soft Part Sarcoma." Archives of Pathology & Laboratory Medicine 123, no. 6 (June 1, 1999): 503–7. http://dx.doi.org/10.5858/1999-123-0503-ipomam.
Full textAbstract:
Abstract Background.—The histogenesis of alveolar soft part sarcoma remains elusive. Myogenic origin is favored, although conflicting data on immunohistochemical demonstration of muscle-associated markers exist. Myogenin and MyoD1, transcription factors of the myogenic determination family, have crucial roles in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage and in maintenance of skeletal muscle phenotype. Their immunohistochemical detection is specific in characterization of rhabdomyosarcoma. Methods.—Antibodies for myogenin, MyoD1, desmin, and muscle-specific actin were employed on a large series of cases (n = 19) of formalin-fixed, paraffin-embedded alveolar soft part sarcoma. Results.—Minimal scattered nuclear staining was seen with myogenin. All cases had pronounced, nonspecific granular cytoplasmic immunostaining with MyoD1; nuclei were negative. All tumors were negative for desmin and muscle-specific actin. Ultrastructural study in 10 cases failed to reveal features of skeletal muscle differentiation. Conclusions.—Cytoplasmic staining with MyoD1 in alveolar soft part sarcoma may correspond to cross-reactivity with an undetermined cytoplasmic antigen. The lack of immunostaining with myogenin, MyoD1, desmin, and muscle-specific actin provides evidence against a myogenic origin for alveolar soft part sarcoma.
6
Bergstrom, Donald A., and Stephen J. Tapscott. "Molecular Distinction between Specification and Differentiation in the Myogenic Basic Helix-Loop-Helix Transcription Factor Family." Molecular and Cellular Biology 21, no. 7 (April 1, 2001): 2404–12. http://dx.doi.org/10.1128/mcb.21.7.2404-2412.2001.
Full textAbstract:
ABSTRACT The myogenic basic helix-loop-helix (bHLH) proteins regulate both skeletal muscle specification and differentiation: MyoD and Myf5 establish the muscle lineage, whereas myogenin mediates differentiation. Previously, we demonstrated that MyoD was more efficient than myogenin at initiating the expression of skeletal muscle genes, and in this study we present the molecular basis for this difference. A conserved amphipathic alpha-helix in the carboxy terminus of the myogenic bHLH proteins has distinct activities in MyoD and myogenin: the MyoD helix facilitates the initiation of endogenous gene expression, whereas the myogenin helix functions as a general transcriptional activation domain. Thus, the alternate use of a similar motif for gene initiation and activation provides a molecular basis for the distinction between specification and differentiation within the myogenic bHLH gene family.
7
Schwarz, J. J., T. Chakraborty, J. Martin, J. M. Zhou, and E. N. Olson. "The basic region of myogenin cooperates with two transcription activation domains to induce muscle-specific transcription." Molecular and Cellular Biology 12, no. 1 (January 1992): 266–75. http://dx.doi.org/10.1128/mcb.12.1.266.
Full textAbstract:
Myogenin is a skeletal muscle-specific transcription factor that can activate myogenesis when introduced into a variety of nonmuscle cell types. Activation of the myogenic program by myogenin is dependent on its binding to a DNA sequence known as an E box, which is associated with numerous muscle-specific genes. Myogenin shares homology with MyoD and other myogenic regulatory factors within a basic region and a helix-loop-helix (HLH) motif that mediate DNA binding and dimerization, respectively. Here we show that the basic region-HLH motif of myogenin alone lacks transcriptional activity and is dependent on domains in the amino and carboxyl termini to activate transcription. Analysis of these N- and C-terminal domains through creation of chimeras with the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that they act as strong transcriptional activators. These transcription activation domains are dependent for activity on a specific amino acid sequence within the basic region, referred to as the myogenic recognition motif (MRM), when an E box is the target for DNA binding. However, the activation domains function independent of the MRM when DNA binding is mediated through a heterologous DNA-binding domain. The activation domain of the acidic coactivator VP16 can substitute for the myogenin activation domains and restore strong myogenic activity to the basic region-HLH motif. Within a myogenin-VP16 chimera, however, the VP16 activation domain also relies on the MRM for activation of the myogenic program. These findings reveal that DNA binding and transcriptional activation are separable functions, encoded by different domains of myogenin, but that the activity of the transcriptional activation domains is influenced by the DNA-binding domain. Activation of muscle-specific transcription requires collaboration between the DNA-binding and activation domains of myogenin and is dependent on events in addition to DNA binding.
8
Schwarz, J. J., T. Chakraborty, J. Martin, J. M. Zhou, and E. N. Olson. "The basic region of myogenin cooperates with two transcription activation domains to induce muscle-specific transcription." Molecular and Cellular Biology 12, no. 1 (January 1992): 266–75. http://dx.doi.org/10.1128/mcb.12.1.266-275.1992.
Full textAbstract:
Myogenin is a skeletal muscle-specific transcription factor that can activate myogenesis when introduced into a variety of nonmuscle cell types. Activation of the myogenic program by myogenin is dependent on its binding to a DNA sequence known as an E box, which is associated with numerous muscle-specific genes. Myogenin shares homology with MyoD and other myogenic regulatory factors within a basic region and a helix-loop-helix (HLH) motif that mediate DNA binding and dimerization, respectively. Here we show that the basic region-HLH motif of myogenin alone lacks transcriptional activity and is dependent on domains in the amino and carboxyl termini to activate transcription. Analysis of these N- and C-terminal domains through creation of chimeras with the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that they act as strong transcriptional activators. These transcription activation domains are dependent for activity on a specific amino acid sequence within the basic region, referred to as the myogenic recognition motif (MRM), when an E box is the target for DNA binding. However, the activation domains function independent of the MRM when DNA binding is mediated through a heterologous DNA-binding domain. The activation domain of the acidic coactivator VP16 can substitute for the myogenin activation domains and restore strong myogenic activity to the basic region-HLH motif. Within a myogenin-VP16 chimera, however, the VP16 activation domain also relies on the MRM for activation of the myogenic program. These findings reveal that DNA binding and transcriptional activation are separable functions, encoded by different domains of myogenin, but that the activity of the transcriptional activation domains is influenced by the DNA-binding domain. Activation of muscle-specific transcription requires collaboration between the DNA-binding and activation domains of myogenin and is dependent on events in addition to DNA binding.
9
Heidt, Analeah B., Anabel Rojas, Ian S. Harris, and Brian L. Black. "Determinants of Myogenic Specificity within MyoD Are Required for Noncanonical E Box Binding." Molecular and Cellular Biology 27, no. 16 (June 11, 2007): 5910–20. http://dx.doi.org/10.1128/mcb.01700-06.
Full textAbstract:
ABSTRACT The MyoD family of basic helix-loop-helix (bHLH) transcription factors has the remarkable ability to induce myogenesis in vitro and in vivo. This myogenic specificity has been mapped to two amino acids in the basic domain, an alanine and threonine, referred to as the myogenic code. These essential determinants of myogenic specificity are conserved in all MyoD family members from worms to humans, yet their function in myogenesis is unclear. Induction of the muscle transcriptional program requires that MyoD be able to locate and stably bind to sequences present in the promoter regions of critical muscle genes. Recent studies have shown that MyoD binds to noncanonical E boxes in the myogenin gene, a critical locus required for myogenesis, through interactions with resident heterodimers of the HOX-TALE transcription factors Pbx1A and Meis1. In the present study, we show that the myogenic code is required for MyoD to bind to noncanonical E boxes in the myogenin promoter and for the formation of a tetrameric complex with Pbx/Meis. We also show that these essential determinants of myogenesis are sufficient to confer noncanonical E box binding to the E12 basic domain. Thus, these data show that noncanonical E box binding correlates with myogenic potential, and we speculate that the myogenic code residues in MyoD function as myogenic determinants via their role in noncanonical E box binding and recognition.
10
Arnold, H. H., C. D. Gerharz, H. E. Gabbert, and A. Salminen. "Retinoic acid induces myogenin synthesis and myogenic differentiation in the rat rhabdomyosarcoma cell line BA-Han-1C." Journal of Cell Biology 118, no. 4 (August 15, 1992): 877–87. http://dx.doi.org/10.1083/jcb.118.4.877.
Full textAbstract:
Two clonal rat rhabdomyosarcoma cell lines BA-Han-1B and BA-Han-1C with different capacities for myogenic differentiation have been examined for the expression of muscle regulatory basic helix-loop-helix (bHLH) proteins of the MyoD family. Whereas cells of the BA-Han-1C subpopulation constitutively expressed MyoD1 and could be induced to differentiate with retinoic acid (RA), BA-Han-1B cells did not express any of the myogenic control factors and appeared to be largely differentiation-defective. Upon induction with RA, BA-Han-1C cells expressed also myogenin, in contrast to BA-Han-1B cells which never activated any of the genes encoding muscle bHLH factors. The onset of myogenin transcription in BA-Han-1C cells required de novo protein synthesis and DNA replication suggesting that RA probably did not act directly on the myogenin gene. Although MyoD1 was expressed in proliferating BA-Han-1C myoblasts, muscle-specific reporter genes were not activated indicating that MyoD was biologically inactive. However, transfections with plasmid expressing additional MyoD1 protein resulted in the transactivation of muscle genes even in the absence of RA. mRNA encoding the negative regulatory HLH protein Id was expressed in proliferating BA-Han-1C cells and disappeared later after RA induction which suggested that it may be involved in the regulation of MyoD1 activity. The myogenic differentiation of malignant rhabdomyosarcoma cells strictly correlated with the activation of the myogenin gene. In fact, stable transfections of BA-Han-1C cells with myogenin expressing plasmids resulted in spontaneous differentiation. Together, our results suggest that the transformed and undifferentiated phenotype of BA-Han-1C rhabdomyosarcoma cells is associated with the inactivation of the myogenic factor MyoD1 as well as lack of myogenin expression. RA alleviates the inhibition of myogenic differentiation, probably by activating MyoD protein and myogenin gene transcription. BA-Han-1B cells did not respond to RA and the differentiated phenotype could not be restored by overexpression of MyoD1 or myogenin.
11
Parker, Maura H., Robert L. S. Perry, Mélanie C. Fauteux, Charlotte A. Berkes, and Michael A. Rudnicki. "MyoD Synergizes with the E-Protein HEBβ To Induce Myogenic Differentiation." Molecular and Cellular Biology 26, no. 15 (August 1, 2006): 5771–83. http://dx.doi.org/10.1128/mcb.02404-05.
Full textAbstract:
ABSTRACT The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate α and β isoforms. While the function of these molecules has been studied in other cell types, questions persist regarding the molecular functions of HEB proteins in skeletal muscle. Our data demonstrate that HEBα expression remains unchanged in both myoblasts and myotubes, whereas HEBβ is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEBβ complex bound the E1 E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEBβ with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEBα and HEBβ synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEBβ by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEBα and HEBβ play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation.
12
Edmondson, D. G., T. C. Cheng, P. Cserjesi, T. Chakraborty, and E. N. Olson. "Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2." Molecular and Cellular Biology 12, no. 9 (September 1992): 3665–77. http://dx.doi.org/10.1128/mcb.12.9.3665.
Full textAbstract:
Transcriptional cascades that specify cell fate have been well described in invertebrates. In mammalian development, however, gene hierarchies involved in determination of cell lineage are not understood. With the recent cloning of the MyoD family of myogenic regulatory factors, a model system has become available with which to study the dynamics of muscle determination in mammalian development. Myogenin, along with other members of the MyoD gene family, possesses the apparent ability to redirect nonmuscle cells into the myogenic lineage. This ability appears to be due to the direct activation of an array of subordinate or downstream genes which are responsible for formation and function of the muscle contractile apparatus. Myogenin-directed transcription has been shown to occur through interaction with a DNA consensus sequence known as an E box (CANNTG) present in the control regions of numerous downstream genes. In addition to activating the transcription of subordinate genes, members of the MyoD family positively regulate their own expression and cross-activate one another's expression. These autoregulatory interactions have been suggested as a mechanism for induction and maintenance of the myogenic phenotype, but the molecular details of the autoregulatory circuits are undefined. Here we show that the myogenin promoter contains a binding site for the myocyte-specific enhancer-binding factor, MEF-2, which can function as an intermediary of myogenin autoactivation. Since MEF-2 can be induced by myogenin, these results suggest that myogenin and MEF-2 participate in a transcriptional cascade in which MEF-2, once induced by myogenin, acts to amplify and maintain the myogenic phenotype by acting as a positive regulator of myogenin expression.
13
Edmondson, D. G., T. C. Cheng, P. Cserjesi, T. Chakraborty, and E. N. Olson. "Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2." Molecular and Cellular Biology 12, no. 9 (September 1992): 3665–77. http://dx.doi.org/10.1128/mcb.12.9.3665-3677.1992.
Full textAbstract:
Transcriptional cascades that specify cell fate have been well described in invertebrates. In mammalian development, however, gene hierarchies involved in determination of cell lineage are not understood. With the recent cloning of the MyoD family of myogenic regulatory factors, a model system has become available with which to study the dynamics of muscle determination in mammalian development. Myogenin, along with other members of the MyoD gene family, possesses the apparent ability to redirect nonmuscle cells into the myogenic lineage. This ability appears to be due to the direct activation of an array of subordinate or downstream genes which are responsible for formation and function of the muscle contractile apparatus. Myogenin-directed transcription has been shown to occur through interaction with a DNA consensus sequence known as an E box (CANNTG) present in the control regions of numerous downstream genes. In addition to activating the transcription of subordinate genes, members of the MyoD family positively regulate their own expression and cross-activate one another's expression. These autoregulatory interactions have been suggested as a mechanism for induction and maintenance of the myogenic phenotype, but the molecular details of the autoregulatory circuits are undefined. Here we show that the myogenin promoter contains a binding site for the myocyte-specific enhancer-binding factor, MEF-2, which can function as an intermediary of myogenin autoactivation. Since MEF-2 can be induced by myogenin, these results suggest that myogenin and MEF-2 participate in a transcriptional cascade in which MEF-2, once induced by myogenin, acts to amplify and maintain the myogenic phenotype by acting as a positive regulator of myogenin expression.
14
Dieli-Conwright, Christina M., Tanya M. Spektor, Judd C. Rice, Fred R. Sattler, and E. Todd Schroeder. "Influence of hormone replacement therapy on eccentric exercise induced myogenic gene expression in postmenopausal women." Journal of Applied Physiology 107, no. 5 (November 2009): 1381–88. http://dx.doi.org/10.1152/japplphysiol.00590.2009.
Full textAbstract:
Hormone replacement therapy (HRT) is used in postmenopausal women to relieve symptoms of menopause and prevent osteoporosis. We sought to evaluate changes in mRNA expression of key myogenic factors in postmenopausal women taking and not taking HRT following a high-intensity eccentric resistance exercise. Fourteen postmenopausal women were studied and included 6 control women not using HRT (59 ± 4 years, 63 ± 17 kg) and 8 women using traditional HRT (59 ± 4 yr, 89 ± 24 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on a Cybex dynamometer at 60°/s. Muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 h after the exercise bout. Gene expression was determined using RT-PCR for follistatin, forkhead box 3A (FOXO3A), muscle atrophy F-box (MAFbx), muscle ring finger-1 (MuRF-1), myogenic differentiation factor (MyoD), myogenin, myostatin, myogenic factor 5 (Myf5), and muscle regulatory factor 4 (MRF4). At rest, the HRT group expressed higher levels of MyoD, myogenin, Myf5, MRF4, and follistatin ( P < 0.05). In response to eccentric exercise, follistatin, MyoD, myogenin, Myf5, and MRF4 were significantly increased ( P ≤ 0.05) and FOXO3A, MAFbx, MuRF-1, and myostatin were significantly decreased in the control and HRT groups ( P ≤ 0.05). Significantly greater changes in mRNA expression of follistatin, FOXO3A, MAFbx, MuRF-1, MyoD, myogenin, myostatin, Myf5, and MRF4 (p≤0.05) occurred in the HRT group than in the control group after exercise. These data suggest that postmenopausal women using HRT express higher myogenic regulatory factor gene expression, which may reflect an attempt to preserve muscle mass. Furthermore, postmenopausal women using HRT experienced a greater myogenic response to maximal eccentric exercise.
15
Martini, Martina, Gabriella Dobrowolny, Michela Aucello, and Antonio Musarò. "Postmitotic Expression of SOD1G93AGene Affects the Identity of Myogenic Cells and Inhibits Myoblasts Differentiation." Mediators of Inflammation 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/537853.
Full textAbstract:
To determine the role of mutant SOD1 gene (SOD1G93A) on muscle cell differentiation, we derived C2C12 muscle cell lines carrying a stably transfected SOD1G93Agene under the control of a myosin light chain (MLC) promoter-enhancer cassette. Expression of MLC/SOD1G93Ain C2C12 cells resulted in dramatic inhibition of myoblast differentiation. Transfected SOD1G93Agene expression in postmitotic skeletal myocytes downregulated the expression of relevant markers of committed and differentiated myoblasts such as MyoD, Myogenin, MRF4, and the muscle specific miRNA expression. The inhibitory effects of SOD1G93Agene on myogenic program perturbed Akt/p70 and MAPK signaling pathways which promote differentiation cascade. Of note, the inhibition of the myogenic program, by transfected SOD1G93Agene expression, impinged also the identity of myogenic cells. Expression of MLC/SOD1G93Ain C2C12 myogenic cells promoted a fibro-adipogenic progenitors (FAPs) phenotype, upregulating HDAC4 protein and preventing the myogenic commitment complex BAF60C-SWI/SNF. We thus identified potential molecular mediators of the inhibitory effects of SOD1G93Aon myogenic program and disclosed potential signaling, activated by SOD1G93A, that affect the identity of the myogenic cell population.
16
Lee, Hojun, and Seung-Jun Choi. "Mild Hyperthermia-Induced Myogenic Differentiation in Skeletal Muscle Cells: Implications for Local Hyperthermic Therapy for Skeletal Muscle Injury." Oxidative Medicine and Cellular Longevity 2018 (June 27, 2018): 1–9. http://dx.doi.org/10.1155/2018/2393570.
Full textAbstract:
The percutaneous application of controlled temperature on damaged muscle is regarded as a prevalent remedy. However, specific mechanisms are not completely understood. Therefore, cellular behaviors of myoblasts were investigated under a physiological hyperthermic temperature. The myoblasts were cultured under no treatment (NT, 37°C, 24 h/day), intermittent heat treatment (IHT, 39°C, 2 h/day), and continuous heat treatment (CHT, 39°C, 24 h/day) during proliferation, migration, or myogenic differentiation. Although the effects of mild heat on migration were not observed, the proliferation was promoted by both IHT and CHT. The myogenic differentiation was also enhanced in a treatment time-dependent manner, as evidenced by an increase in myotube size and fusion index. The gene expressions of mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam), a subset of mitochondrial dynamics (Mfn1 and Drp1), and a myogenic regulatory factor (myogenin) were increased in a heat treatment time-dependent manner. Interestingly, the mild heat-induced myogenic differentiation and myogenin expression were retarded significantly in PGC-1α-targeted siRNA-transfected cells, suggesting that mild hyperthermia promotes myogenic differentiation via the modulation of PGC-1α. This study provides cellular evidence supporting that local hyperthermic treatment at 39°C is regarded as an effective therapeutic strategy to promote satellite cell activities in regenerating myofibers.
17
Goichberg, P., M. Shtutman, A. Ben-Ze'ev, and B. Geiger. "Recruitment of (β)-catenin to cadherin-mediated intercellular adhesions is involved in myogenic induction." Journal of Cell Science 114, no. 7 (April 1, 2001): 1309–19. http://dx.doi.org/10.1242/jcs.114.7.1309.
Full textAbstract:
Cadherin-mediated cell adhesion is involved in muscle differentiation from early stages of myogenic induction to late stages of myoblast interaction and fusion. (β)-Catenin is a major constituent of cadherin-based adherens junctions and also serves as a signal transduction molecule that regulates gene expression during development. In this study, we explored the involvement of (β)-catenin in myogenic differentiation. We show here that shortly after a switch from growth to differentiation medium, (β)-catenin translocates to cell-cell junctions and its levels increase. We further show that elevation of (β)-catenin levels, induced either by inhibition of its breakdown, using LiCl, or by its overexpression, suppresses the formation of adherens junctions, resulting in a sharp decline in myogenin expression and an arrest of myogenic progression. Recruitment of (β)-catenin to adherens junctions after transfection with N-cadherin restores myogenin expression in the transfected cells. These results suggest that increased cadherin-mediated adhesion and translocation of (β)-catenin to adherens junctions are involved in activating the early steps of myogenic differentiation.
18
Cusella-De Angelis, M. G., G. Lyons, C. Sonnino, L. De Angelis, E. Vivarelli, K. Farmer, W. E. Wright, M. Molinaro, M. Bouchè, and M. Buckingham. "MyoD, myogenin independent differentiation of primordial myoblasts in mouse somites." Journal of Cell Biology 116, no. 5 (March 1, 1992): 1243–55. http://dx.doi.org/10.1083/jcb.116.5.1243.
Full textAbstract:
The accumulation of two myogenic regulatory proteins, MyoD and myogenin, was investigated by double-immunocytochemistry and correlated with myosin heavy chain expression in different classes of myoblasts in culture and during early myogenesis in vivo. During in vitro differentiation of fetal myoblasts, MyoD-positive cells were detected first, followed by the appearance of cells positive for both MyoD and myogenin and finally by the appearance of differentiated myocytes and myotubes expressing myosin heavy chain (MHC). A similar pattern of expression was observed in cultures of embryonic and satellite cells. In contrast, most myogenic cells isolated from newly formed somites, expressed MHC in the absence of detectable levels of myogenin or MyoD. In vivo, the appearance of both myogenin and MyoD proteins was only detected at 10.5 d postcoitum (d.p.c.), when terminally differentiated muscle cells could already be identified in the myotome. Parasagittal sections of the caudal myotomes of 10.5-d-old embryos showed that expression of contractile proteins preceded the expression of myogenin or MyoD and, when coexpressed, MHC and myogenin did not co-localize within all the cells of the myotome. In the limb bud, however, many myogenin (or MyoD) positive/MHC negative cells could be observed in the proximal region at day 11. During further embryonic development the expression of these proteins remained constant in all the muscle anlagens examined, decreasing to a low level during the late fetal period. Western and Northern analysis confirmed that the myogenin protein could only be detected after 10.5 d.p.c. while the corresponding message was clearly present at 9.5 d.p.c., strongly suggesting a posttranscriptional regulation of myogenin during this stage of embryonic development. These data show that the first myogenic cells which appear in the mouse myotome, and can be cultured from it, accumulate muscle structural proteins in their cytoplasm without expressing detectable levels of myogenin protein (although the message is clearly accumulated). Neither MyoD message or protein are detectable in these cells, which may represent a distinct myogenic population whose role in development remains to be established.
19
Tiffin, Nicki, Saleh Adi, David Stokoe, Nan-Yan Wu, and Stephen M. Rosenthal. "Akt Phosphorylation Is Not Sufficient for Insulin-Like Growth Factor-Stimulated Myogenin Expression but Must Be Accompanied by Down-Regulation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Phosphorylation." Endocrinology 145, no. 11 (November 1, 2004): 4991–96. http://dx.doi.org/10.1210/en.2004-0101.
Full textAbstract:
Abstract IGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially, IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory factor essential for myogenesis. Subsequently, IGF-I switches to stimulating expression of myogenin. The mechanisms that mediate this switch in IGF action are incompletely understood. Several laboratories have demonstrated that the phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic differentiation and have suggested that this pathway mediates IGF-I stimulation of myogenin mRNA expression, an early critical step in the differentiation process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2 phosphorylation, the latter of which is also known to regulate myogenic differentiation. In the present study in rat L6E9 muscle cells, we have manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin mRNA expression in response to treatment with IGF-I. We find that even in the presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt phosphorylation may be necessary, it is not sufficient for induction of myogenic differentiation by IGF-I and must be accompanied by a decrease in ERK1/2 phosphorylation.
20
Smith, T. H., N. E. Block, S. J. Rhodes, S. F. Konieczny, and J. B. Miller. "A unique pattern of expression of the four muscle regulatory factor proteins distinguishes somitic from embryonic, fetal and newborn mouse myogenic cells." Development 117, no. 3 (March 1, 1993): 1125–33. http://dx.doi.org/10.1242/dev.117.3.1125.
Full textAbstract:
A unique pattern of expression of the four muscle regulatory factor (MRF) proteins was found to distinguish early somitic from embryonic, fetal and newborn limb myogenic cells in vitro. Expression of the myosin heavy chain (MHC), MyoD, myogenin, Myf-5, and MRF4 proteins was examined by immunocytochemistry in cultures of four distinct types of mouse myogenic cells: somitic (E8.5), embryonic (E11.5), fetal (E16.5) and newborn limb. In embryonic, fetal and newborn cultures, the MRF proteins were expressed in generally similar patterns: MyoD was the first MRF expressed; MyoD and myogenin were expressed by more cells than Myf-5 or MRF4; and each of the four MRFs was found both in cells that expressed MHC and in cells that did not express MHC. In cultures of somitic cells, in contrast, Myf-5 was expressed first and by more cells than MyoD or myogenin; MRF4 was not detected; and the MRFs were never found to be coexpressed with MHC in the same cell. Thus, some somitic cells had the unexpected ability to maintain MHC expression in the absence of detectable MRF protein expression. The different myogenic programs of embryonic, fetal and newborn myogenic cells are not, therefore, a simple result of qualitatively different MRF expression patterns, whereas myogenesis by somitic cells does include a unique pattern of MRF expression.
21
Li, L., R. Heller-Harrison, M. Czech, and E. N. Olson. "Cyclic AMP-dependent protein kinase inhibits the activity of myogenic helix-loop-helix proteins." Molecular and Cellular Biology 12, no. 10 (October 1992): 4478–85. http://dx.doi.org/10.1128/mcb.12.10.4478.
Full textAbstract:
Differentiation of skeletal muscle cells is inhibited by the cyclic AMP (cAMP) signal transduction pathway. Here we report that the catalytic subunit of cAMP-dependent protein kinase (PKA) can substitute for cAMP and suppress muscle-specific transcription by silencing the activity of the MyoD family of regulatory factors, which includes MyoD, myogenin, myf5, and MRF4. Repression by the PKA catalytic (C) subunit is directed at the consensus sequence CANNTG, the target for DNA binding and transcriptional activation by these myogenic regulators. Phosphopeptide mapping of myogenin in vitro and in vivo revealed two PKA phosphorylation sites, both within the basic region. However, repression of myogenin function by PKA does not require direct phosphorylation of these sites but instead involves an indirect mechanism with one or more intermediate steps. Regulation of the transcriptional activity of the MyoD family by modulation of the cAMP signaling pathway may account for the inhibitory effects of certain peptide growth factors on muscle-specific gene expression and may also determine the responsiveness of different cell types to myogenic conversion by these myogenic regulators.
22
Li, L., R. Heller-Harrison, M. Czech, and E. N. Olson. "Cyclic AMP-dependent protein kinase inhibits the activity of myogenic helix-loop-helix proteins." Molecular and Cellular Biology 12, no. 10 (October 1992): 4478–85. http://dx.doi.org/10.1128/mcb.12.10.4478-4485.1992.
Full textAbstract:
Differentiation of skeletal muscle cells is inhibited by the cyclic AMP (cAMP) signal transduction pathway. Here we report that the catalytic subunit of cAMP-dependent protein kinase (PKA) can substitute for cAMP and suppress muscle-specific transcription by silencing the activity of the MyoD family of regulatory factors, which includes MyoD, myogenin, myf5, and MRF4. Repression by the PKA catalytic (C) subunit is directed at the consensus sequence CANNTG, the target for DNA binding and transcriptional activation by these myogenic regulators. Phosphopeptide mapping of myogenin in vitro and in vivo revealed two PKA phosphorylation sites, both within the basic region. However, repression of myogenin function by PKA does not require direct phosphorylation of these sites but instead involves an indirect mechanism with one or more intermediate steps. Regulation of the transcriptional activity of the MyoD family by modulation of the cAMP signaling pathway may account for the inhibitory effects of certain peptide growth factors on muscle-specific gene expression and may also determine the responsiveness of different cell types to myogenic conversion by these myogenic regulators.
23
Moore, J. W., C. Dionne, M. Jaye, and J. L. Swain. "The mRNAs encoding acidic FGF, basic FGF and FGF receptor are coordinately downregulated during myogenic differentiation." Development 111, no. 3 (March 1, 1991): 741–48. http://dx.doi.org/10.1242/dev.111.3.741.
Full textAbstract:
Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that exert pleiotropic effects in a range of cell types including skeletal myocytes. Previous studies demonstrate that exogenously supplied FGFs stimulate proliferation of myoblasts and inhibit their differentiation in culture, but little information is available concerning endogenous expression of FGFs by skeletal myocytes. In this study acidic and basic FGF mRNAs were found to be expressed in murine and rat skeletal muscle, and expression was demonstrated to vary with the tissue and species examined. Myogenic cell lines were then analyzed to determine if FGFs are expressed in myoblasts, and if so, whether expression is regulated during myogenic differentiation. Murine Sol 8 and rat L6 myoblasts were found to express acidic and basic FGF mRNAs, and the expression of both growth factors was downregulated at the transcriptional level during myogenic differentiation. A decrease in expression of the mouse homologue of the human FGF receptor paralleled the decrease in acidic and basic FGF mRNAs in Sol 8 cells, indicating that the decrease in FGF receptor abundance previously observed during myogenic differentiation is regulated at the mRNA level. The results of this study suggest that a coordinate decrease in endogenously produced acidic and basic FGFs and their cognate receptor may participate in the regulation of myogenic differentiation. Furthermore, the observation that expression of a myogenic determination gene, myogenin, increases as FGF transcripts decline, together with previous data demonstrating suppression of myogenin expression by FGF, suggest a mechanism whereby endogenously produced FGFs may exert their effect on differentiation.
24
Huang, Yao, Ji Li, Yongjun Zhang, and Chuanyue Wu. "The Roles of Integrin-Linked Kinase in the Regulation of Myogenic Differentiation." Journal of Cell Biology 150, no. 4 (August 21, 2000): 861–72. http://dx.doi.org/10.1083/jcb.150.4.861.
Full textAbstract:
Myogenic differentiation is a highly orchestrated, multistep process that is coordinately regulated by growth factors and cell adhesion. We show here that integrin-linked kinase (ILK), an intracellular integrin– and PINCH-binding serine/threonine protein kinase, is an important regulator of myogenic differentiation. ILK is abundantly expressed in C2C12 myoblasts, both before and after induction of terminal myogenic differentiation. However, a noticeable amount of ILK in the Triton X-100–soluble cellular fractions is significantly reduced during terminal myogenic differentiation, suggesting that ILK is involved in cellular control of myogenic differentiation. To further investigate this, we have overexpressed the wild-type and mutant forms of ILK in C2C12 myoblasts. Overexpression of ILK in the myoblasts inhibited the expression of myogenic proteins (myogenin, MyoD, and myosin heavy chain) and the subsequent formation of multinucleated myotubes. Furthermore, mutations that eliminate either the PINCH-binding or the kinase activity of ILK abolished its ability to inhibit myogenic protein expression and allowed myotube formation. Although overexpression of the ILK mutants is permissive for the initiation of terminal myogenic differentiation, the myotubes derived from myoblasts overexpressing the ILK mutants frequently exhibited an abnormal morphology (giant myotubes containing clustered nuclei), suggesting that ILK functions not only in the initial decision making process, but also in later stages (fusion or maintaining myotube integrity) of myogenic differentiation. Additionally, we show that overexpression of ILK, but not that of the PINCH-binding defective or the kinase-deficient ILK mutants, prevents inactivation of MAP kinase, which is obligatory for the initiation of myogenic differentiation. Finally, inhibition of MAP kinase activation reversed the ILK-induced suppression of myogenic protein expression. Thus, ILK likely influences the initial decision making process of myogenic differentiation by regulation of MAP kinase activation.
25
Sabourin, Luc A., Adele Girgis-Gabardo, Patrick Seale, Atsushi Asakura, and Michael A. Rudnicki. "Reduced Differentiation Potential of Primary MyoD−/− Myogenic Cells Derived from Adult Skeletal Muscle." Journal of Cell Biology 144, no. 4 (February 22, 1999): 631–43. http://dx.doi.org/10.1083/jcb.144.4.631.
Full textAbstract:
To gain insight into the regeneration deficit of MyoD−/− muscle, we investigated the growth and differentiation of cultured MyoD−/− myogenic cells. Primary MyoD−/− myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD−/− myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD−/− myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD−/− cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD−/− myogenic cells. Mixing of lacZ-labeled MyoD−/− cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD−/− myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.
26
Yu, Yu, Lihua Qi, Junzhou Wu, Yunling Wang, Weigang Fang, and Hongquan Zhang. "Kindlin 2 Regulates Myogenic Related Factor Myogenin via a Canonical Wnt Signaling in Myogenic Differentiation." PLoS ONE 8, no. 5 (May 22, 2013): e63490. http://dx.doi.org/10.1371/journal.pone.0063490.
Full text
27
Raue, Ulrika, Dustin Slivka, Bozena Jemiolo, Chris Hollon, and Scott Trappe. "Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women." Journal of Applied Physiology 101, no. 1 (July 2006): 53–59. http://dx.doi.org/10.1152/japplphysiol.01616.2005.
Full textAbstract:
The purpose of this study was to investigate mRNA expression of several key skeletal muscle myogenic controllers; myogenic differentiation factor (MyoD), muscle regulatory factor 4 (MRF4), myogenic factor 5 (Myf5), myogenin, myostatin, and myocyte enhancer factor 2 (MEF2) at rest and 4 h after a single bout of resistance exercise (RE) in young and old women. Eight young women (YW; 23 ± 2 yr, 67 ± 5 kg) and six old women (OW; 85 ± 1 yr, 67 ± 4 kg) performed 3 sets of 10 repetitions of bilateral knee extensions at 70% of one repetition maximum. Muscle biopsies were taken from the vastus lateralis before and 4 h after RE. Using real-time RT PCR, mRNA from the muscle samples was amplified and normalized to GAPDH. At rest, OW expressed higher ( P < 0.05) levels of MyoD, MRF4, Myf5, myogenin, and myostatin compared with YW. In response to RE, there was a main time effect ( P < 0.05) for the YW and OW combined in the upregulation of MyoD (2.0-fold) and MRF4 (1.4-fold) and in the downregulation of myostatin (2.2-fold). There was a trend ( P = 0.08) for time × age interaction in MRF4. These data show that old women express higher myogenic mRNA levels at rest. The higher resting myogenic mRNA levels in old women may reflect an attempt to preserve muscle mass and function. When challenged with RE, old women appear to respond in a similar manner as young women.
28
Asfour, Hasan A., Mohammed Z. Allouh, and Raed S. Said. "Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery." Experimental Biology and Medicine 243, no. 2 (January 2018): 118–28. http://dx.doi.org/10.1177/1535370217749494.
Full textAbstract:
Prenatal and postnatal myogenesis share many cellular and molecular aspects. Myogenic regulatory factors are basic Helix-Loop-Helix transcription factors that indispensably regulate both processes. These factors (Myf5, MyoD, Myogenin, and MRF4) function as an orchestrating cascade, with some overlapped actions. Prenatally, myogenic regulatory factors are restrictedly expressed in somite-derived myogenic progenitor cells and their derived myoblasts. Postnatally, myogenic regulatory factors are important in regulating the myogenesis process via satellite cells. Many positive and negative regulatory mechanisms exist either between myogenic regulatory factors themselves or between myogenic regulatory factors and other proteins. Upstream factors and signals are also involved in the control of myogenic regulatory factors expression within different prenatal and postnatal myogenic cells. Here, the authors have conducted a thorough and an up-to-date review of the myogenic regulatory factors since their discovery 30 years ago. This review discusses the myogenic regulatory factors structure, mechanism of action, and roles and regulations during prenatal and postnatal myogenesis. Impact statement Myogenic regulatory factors (MRFs) are key players in the process of myogenesis. Despite a considerable amount of literature regarding these factors, their exact mechanisms of actions are still incompletely understood with several overlapped functions. Herein, we revised what has hitherto been reported in the literature regarding MRF structures, molecular pathways that regulate their activities, and their roles during pre- and post-natal myogenesis. The work submitted in this review article is considered of great importance for researchers in the field of skeletal muscle formation and regeneration, as it provides a comprehensive summary of all the biological aspects of MRFs and advances a better understanding of the cellular and molecular mechanisms regulating myogenesis. Indeed, attaining a better understanding of MRFs could be utilized in developing novel therapeutic protocols for multiple myopathies.
29
Scales, J. B., E. N. Olson, and M. Perry. "Two distinct Xenopus genes with homology to MyoD1 are expressed before somite formation in early embryogenesis." Molecular and Cellular Biology 10, no. 4 (April 1990): 1516–24. http://dx.doi.org/10.1128/mcb.10.4.1516.
Full textAbstract:
The myogenic factors MyoD1 and myogenin contain a conserved region with similarity to the myc family of proto-oncogenes. To identify amphibian genes structurally and functionally related to these myogenic factors, we screened a Xenopus laevis embryo cDNA library under conditions of reduced stringency with probes corresponding to the myc-like helix-loop-helix motif of mouse MyoD1 and myogenin. Several distinct cDNAs that are highly related to each other and share extensive homology to MyoD1 were isolated. Transcripts from two of these genes, Xlmf1 and Xlmf25 (X. laevis myogenic factor), reach maximal levels of accumulation during gastrulation, remain at constant levels through early embryogenesis, and are found exclusively in skeletal muscles of adult frogs. The appearance of these transcripts early in development precedes the expression of cardiac alpha-actin, a molecular marker for mesoderm formation. A third cDNA, Xlmf11, contains an internal 351-base-pair deletion downstream of the myc homology region and encodes a truncated version of the protein encoded by Xlmf1. When expressed in mouse pluripotential stem cells, Xlmf1 activates the muscle cell differentiation program, resulting in expression of endogenous MyoD1, myogenin, and myosin heavy-chain genes and formation of multinucleated myotubes.
30
Scales, J. B., E. N. Olson, and M. Perry. "Two distinct Xenopus genes with homology to MyoD1 are expressed before somite formation in early embryogenesis." Molecular and Cellular Biology 10, no. 4 (April 1990): 1516–24. http://dx.doi.org/10.1128/mcb.10.4.1516-1524.1990.
Full textAbstract:
The myogenic factors MyoD1 and myogenin contain a conserved region with similarity to the myc family of proto-oncogenes. To identify amphibian genes structurally and functionally related to these myogenic factors, we screened a Xenopus laevis embryo cDNA library under conditions of reduced stringency with probes corresponding to the myc-like helix-loop-helix motif of mouse MyoD1 and myogenin. Several distinct cDNAs that are highly related to each other and share extensive homology to MyoD1 were isolated. Transcripts from two of these genes, Xlmf1 and Xlmf25 (X. laevis myogenic factor), reach maximal levels of accumulation during gastrulation, remain at constant levels through early embryogenesis, and are found exclusively in skeletal muscles of adult frogs. The appearance of these transcripts early in development precedes the expression of cardiac alpha-actin, a molecular marker for mesoderm formation. A third cDNA, Xlmf11, contains an internal 351-base-pair deletion downstream of the myc homology region and encodes a truncated version of the protein encoded by Xlmf1. When expressed in mouse pluripotential stem cells, Xlmf1 activates the muscle cell differentiation program, resulting in expression of endogenous MyoD1, myogenin, and myosin heavy-chain genes and formation of multinucleated myotubes.
31
Wyzykowski, Jeffrey C., Therry I. Winata, Natalia Mitin, Elizabeth J. Taparowsky, and Stephen F. Konieczny. "Identification of Novel MyoD Gene Targets in Proliferating Myogenic Stem Cells." Molecular and Cellular Biology 22, no. 17 (September 1, 2002): 6199–208. http://dx.doi.org/10.1128/mcb.22.17.6199-6208.2002.
Full textAbstract:
ABSTRACT A major control point for skeletal myogenesis revolves around the muscle basic helix-loop-helix gene family that includes MyoD, Myf-5, myogenin, and MRF4. Myogenin and MRF4 are thought to be essential to terminal differentiation events, whereas MyoD and Myf-5 are critical to establishing the myogenic cell lineage and producing committed, undifferentiated myogenic stem cells (myoblasts). Although mouse genetic studies have revealed the importance of MyoD and Myf-5 for myoblast development, the genetic targets of MyoD and Myf-5 activity in undifferentiated myoblasts remain unknown. In this study, we investigated the function of MyoD as a transcriptional activator in undifferentiated myoblasts. By using conditional expression of MyoD, in conjunction with suppression subtractive hybridizations, we show that the Id3 and NP1 (neuronal pentraxin 1) genes become transcriptionally active following MyoD induction in undifferentiated myoblasts. Activation of Id3 and NP1 represents a stable, heritable event that does not rely on continued MyoD activity and is not subject to negative regulation by an activated H-Ras G12V protein. These results are the first to demonstrate that MyoD functions as a transcriptional activator in myogenic stem cells and that this key myogenic regulatory factor exhibits different gene target specificities, depending upon the cellular environment.
32
Fujisawa-Sehara, A., Y. Nabeshima, Y. Hosoda, T. Obinata, and Y. Nabeshima. "Myogenin contains two domains conserved among myogenic factors." Journal of Biological Chemistry 265, no. 25 (September 1990): 15219–23. http://dx.doi.org/10.1016/s0021-9258(18)77244-x.
Full text
33
Wang, Haixia, Qing Xu, Fang Xiao, Yong Jiang, and Zhenguo Wu. "Involvement of the p38 Mitogen-activated Protein Kinase α, β, and γ Isoforms in Myogenic Differentiation." Molecular Biology of the Cell 19, no. 4 (April 2008): 1519–28. http://dx.doi.org/10.1091/mbc.e07-08-0817.
Full textAbstract:
We and others previously showed that p38 mitogen-activated protein kinase is indispensable for myogenic differentiation. However, it is less clear which of the four p38 isoforms in the mouse genome participates in this process. Using C2C12 myogenic cells as a model, we showed here that p38α, β, and γ are expressed with distinct expression patterns during differentiation. Knockdown of any of them by small interfering RNA inhibits myogenic differentiation, which suggests that the functions of the three p38 isoforms are not completely redundant. To further elucidate the unique role of each p38 isoform in myogenic differentiation, we individually knocked down one p38 isoform at a time in C2C12 cells, and we compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, whereas others are uniquely regulated by one particular p38 isoform. Furthermore, several novel p38 target genes (i.e., E2F2, cyclin D3, and WISP1) are found to be required for myogenin expression, which provides a molecular basis to explain why different p38 isoforms are required for myogenic differentiation.
34
Vissing, Kristian, Jesper L. Andersen, Stephen D. R. Harridge, Claudia Sandri, Andreas Hartkopp, Michael Kjaer, and Peter Schjerling. "Gene expression of myogenic factors and phenotype-specific markers in electrically stimulated muscle of paraplegics." Journal of Applied Physiology 99, no. 1 (July 2005): 164–72. http://dx.doi.org/10.1152/japplphysiol.01172.2004.
Full textAbstract:
The transcription factors myogenin and MyoD have been suggested to be involved in maintaining slow and fast muscle-fiber phenotypes, respectively, in rodents. Whether this is also the case in human muscle is unknown. To test this, 4 wk of chronic, low-frequency electrical stimulation training of the tibialis anterior muscle of paraplegic subjects were used to evoke a fast-to-slow transformation in muscle phenotype. It was hypothesized that this would result from an upregulation of myogenin and a downregulation of MyoD. The training evoked the expected mRNA increase for slow fiber-specific markers myosin heavy chain I and 3-hydroxyacyl-CoA dehydrogenase A, whereas an mRNA decrease was seen for fast fiber-specific markers myosin heavy chain IIx and glycerol phosphate dehydrogenase. Although the slow fiber-specific markers citrate synthase and muscle fatty acid binding protein did not display a significant increase in mRNA, they did tend to increase. As hypothesized, myogenin mRNA was upregulated. However, contrary to the hypothesis, MyoD mRNA also increased, although later than myogenin. The mRNA levels of the other myogenic regulatory factor family members, myogenic factor 5 and myogenic regulatory factor 4, and the myocyte enhancer factor (MEF) family members, MEF-2A and MEF-2C, did not change. The results indicate that myogenin is indeed involved in the regulation of the slow oxidative phenotype in human skeletal muscle fibers, whereas MyoD appears to have a more complex regulatory function.
35
Bhullar, Amritpal S., Charles T. Putman, and Vera C. Mazurak. "Potential Role of Omega-3 Fatty Acids on the Myogenic Program of Satellite Cells." Nutrition and Metabolic Insights 9 (January 2016): NMI.S27481. http://dx.doi.org/10.4137/nmi.s27481.
Full textAbstract:
Skeletal muscle loss is associated with aging as well as pathological conditions. Satellite cells (SCs) play an important role in muscle regeneration. Omega-3 fatty acids are widely studied in a variety of muscle wasting diseases; however, little is known about their impact on skeletal muscle regeneration. The aim of this review is to evaluate studies examining the effect of omega-3 fatty acids, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on the regulation of SC proliferation and differentiation. This review highlights mechanisms by which omega-3 fatty acids may modulate the myogenic program of the stem cell population within skeletal muscles and identifies considerations for future studies. It is proposed that minimally three myogenic transcriptional regulatory factors, paired box 7 (Pax7), myogenic differentiation 1 protein, and myogenin, should be measured to confirm the stage of SCs within the myogenic program affected by omega-3 fatty acids.
36
Thinakaran, Gopal, and Jnanankur Bag. "Regulation of c-jun/AP-1 expression in rat L6 myoblasts." Biochemistry and Cell Biology 71, no. 3-4 (March 1, 1993): 197–204. http://dx.doi.org/10.1139/o93-031.
Full textAbstract:
Myogenic differentiation of skeletal myoblasts in culture is triggered by withdrawal of serum mitogens. Expression of one of the serum-inducible, immediate early genes, the protooncogene c-jun, is maintained under low-serum conditions during myogenic differentiation of L6 myoblasts. In this report we have used agents that modulate protein kinases and Ca2+ levels to investigate how the expression of c-jun and myogenin mRNA and also the activator protein 1 (AP-1) DNA-binding activity are regulated in differentiating L6 cells. Our results show that expression of c-jun and myogenin are regulated independent of each other. Furthermore, down regulation of c-jun expression does not cause an increase in myogenin expression, suggesting that c-jun does not suppress myogenin expression in these cells. Electrophoretic mobility shift and ultraviolet cross-linking analyses revealed that the AP-1 complexes of proliferating myoblasts and differentiating myotubes are formed of similar set of polypeptides, and the AP-1 binding activity is probably modulated by posttranslational modifications in differentiating L6 cells.Key words: myogenin, protein kinase C, cAMP, Ca2+, muscle differentiation.
37
Taylor, D. A., V. B. Kraus, J. J. Schwarz, E. N. Olson, and W. E. Kraus. "E1A-mediated inhibition of myogenesis correlates with a direct physical interaction of E1A12S and basic helix-loop-helix proteins." Molecular and Cellular Biology 13, no. 8 (August 1993): 4714–27. http://dx.doi.org/10.1128/mcb.13.8.4714.
Full textAbstract:
The observation that adenovirus E1A gene products can inhibit differentiation of skeletal myocytes suggested that E1A may interfere with the activity of myogenic basic helix-loop-helix (bHLH) transcription factors. We have examined the ability of E1A to mediate repression of the muscle-specific creatine kinase (MCK) gene. Both the E1A12S and E1A13S products repressed MCK transcription in a concentration-dependent fashion. In contrast, amino-terminal deletion mutants (d2-36 and d15-35) of E1A12S were defective for repression. E1A12S also repressed expression of a promoter containing a multimer of the MCK high-affinity E box (the consensus site for myogenic bHLH protein binding) that was dependent, in C3H10T1/2 cells, on coexpression of a myogenin bHLH-VP16 fusion protein. A series of coprecipitation experiments with glutathione S-transferase fusion and in vitro-translated proteins demonstrated that E1A12S, but not amino-terminal E1A deletion mutants, could bind to full-length myogenin and E12 and to deletion mutants of myogenin and E12 that spare the bHLH domains. Thus, the bHLH domains of myogenin and E12, and the high-affinity E box, are targets for E1A-mediated repression of the MCK enhancer, and domains of E1A required for repression of muscle-specific gene transcription also mediate binding to bHLH proteins. We conclude that E1A mediates repression of muscle-specific gene transcription through its amino-terminal domain and propose that this may involve a direct physical interaction between E1A and the bHLH region of myogenic determination proteins.
38
Taylor, D. A., V. B. Kraus, J. J. Schwarz, E. N. Olson, and W. E. Kraus. "E1A-mediated inhibition of myogenesis correlates with a direct physical interaction of E1A12S and basic helix-loop-helix proteins." Molecular and Cellular Biology 13, no. 8 (August 1993): 4714–27. http://dx.doi.org/10.1128/mcb.13.8.4714-4727.1993.
Full textAbstract:
The observation that adenovirus E1A gene products can inhibit differentiation of skeletal myocytes suggested that E1A may interfere with the activity of myogenic basic helix-loop-helix (bHLH) transcription factors. We have examined the ability of E1A to mediate repression of the muscle-specific creatine kinase (MCK) gene. Both the E1A12S and E1A13S products repressed MCK transcription in a concentration-dependent fashion. In contrast, amino-terminal deletion mutants (d2-36 and d15-35) of E1A12S were defective for repression. E1A12S also repressed expression of a promoter containing a multimer of the MCK high-affinity E box (the consensus site for myogenic bHLH protein binding) that was dependent, in C3H10T1/2 cells, on coexpression of a myogenin bHLH-VP16 fusion protein. A series of coprecipitation experiments with glutathione S-transferase fusion and in vitro-translated proteins demonstrated that E1A12S, but not amino-terminal E1A deletion mutants, could bind to full-length myogenin and E12 and to deletion mutants of myogenin and E12 that spare the bHLH domains. Thus, the bHLH domains of myogenin and E12, and the high-affinity E box, are targets for E1A-mediated repression of the MCK enhancer, and domains of E1A required for repression of muscle-specific gene transcription also mediate binding to bHLH proteins. We conclude that E1A mediates repression of muscle-specific gene transcription through its amino-terminal domain and propose that this may involve a direct physical interaction between E1A and the bHLH region of myogenic determination proteins.
39
Nguyen, Mai Thi, Kyung-Ho Min, and Wan Lee. "MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1." International Journal of Molecular Sciences 21, no. 24 (December 11, 2020): 9445. http://dx.doi.org/10.3390/ijms21249445.
Full textAbstract:
Skeletal myogenesis is a multi-stage process that includes the cell cycle exit, myogenic transcriptional activation, and morphological changes to form multinucleated myofibers. Recent studies have shown that saturated fatty acids (SFA) and miRNAs play crucial roles in myogenesis and muscle homeostasis. Nevertheless, the target molecules and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study investigated the critical role played by miR-96-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) significantly reduced FHL1 expression and inhibited the myogenic differentiation of C2C12 myoblasts but induced miR-96-5p expression. The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Interestingly, miR-96-5p suppressed FHL1 expression by directly targeting the 3’UTR of FHL1 mRNA. The transfection of an miR-96-5p mimic upregulated the expressions of cell cycle-related genes, such as PCNA, CCNB1, and CCND1, and increased myoblast proliferation. Moreover, the miR-96-5p mimic inhibited the expressions of myogenic factors, such as myoblast determination protein (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (MEF2C), and myosin heavy chain (MyHC), and dramatically impeded differentiation and fusion of myoblasts. Overall, this study highlights the role of miR-96-5p in myogenesis via FHL1 suppression and suggests a novel regulatory mechanism for myogenesis mediated by miRNA in a background of obesity.
40
Rı́os, Ramón, Isabel Carneiro, Víctor M. Arce, and Jesús Devesa. "Myostatin is an inhibitor of myogenic differentiation." American Journal of Physiology-Cell Physiology 282, no. 5 (May 1, 2002): C993—C999. http://dx.doi.org/10.1152/ajpcell.00372.2001.
Full textAbstract:
Myostatin (MSTN), a transforming growth factor (TGF)-β superfamily member, has been shown to negatively regulate muscle growth by inhibiting muscle precursor cell proliferation. Here, we stably transfected C2C12 cells with mouse MSTN cDNA to investigate its possible role in myoblast differentiation. We found that MSTN cDNA overexpression reversibly inhibits the myogenic process by downregulating mRNA levels of the muscle regulatory factors myoD and myogenin, as well as the activity of their downstream target creatine kinase. Taking into consideration that MSTN expression during development is restricted to muscle, our results suggest that MSTN probably regulates myogenic differentiation by an autocrine mechanism.
41
Cserjesi, P., B. Lilly, L. Bryson, Y. Wang, D. A. Sassoon, and E. N. Olson. "MHox: a mesodermally restricted homeodomain protein that binds an essential site in the muscle creatine kinase enhancer." Development 115, no. 4 (August 1, 1992): 1087–101. http://dx.doi.org/10.1242/dev.115.4.1087.
Full textAbstract:
Myogenic helix-loop-helix (HLH) proteins, such as myogenin and MyoD, can activate muscle-specific transcription when introduced into a variety of nonmuscle cell types. Whereas cells of mesodermal origin are especially permissive to the actions of these myogenic regulators, many other cell types are refractory to myogenic conversion by them. Here we describe a novel homeodomain protein, MHox, that binds an A+T-rich element in the muscle creatine kinase (MCK) enhancer that is essential for muscle-specific transcription and trans-activation by myogenic HLH proteins. MHox is completely restricted to mesodermally derived cell types during embryogenesis and to established cell lines of mesodermal origin. In contrast to most other homeobox genes, MHox expression is excluded from the nervous system, with the highest levels observed in limb bud and visceral arches. In adult mice, MHox is expressed at high levels in skeletal muscle, heart and uterus. The DNA-binding properties and pattern of MHox expression are unique among homeobox genes and suggest a role for MHox as a transcriptional regulator that participates in the establishment of diverse mesodermal cell types.
42
Blagden, Chris S., Larry Fromm, and Steven J. Burden. "Accelerated Response of the myogenin Gene to Denervation in Mutant Mice Lacking Phosphorylation of Myogenin at Threonine 87." Molecular and Cellular Biology 24, no. 5 (March 1, 2004): 1983–89. http://dx.doi.org/10.1128/mcb.24.5.1983-1989.2004.
Full textAbstract:
ABSTRACT Gene expression in skeletal muscle is regulated by a family of myogenic basic helix-loop-helix (bHLH) proteins. The binding of these bHLH proteins, notably MyoD and myogenin, to E-boxes in their own regulatory regions is blocked by protein kinase C (PKC)-mediated phosphorylation of a single threonine residue in their basic region. Because electrical stimulation increases PKC activity in skeletal muscle, these data have led to an attractive model suggesting that electrical activity suppresses gene expression by stimulating phosphorylation of this critical threonine residue in myogenic bHLH proteins. We show that electrical activity stimulates phosphorylation of myogenin at threonine 87 (T87) in vivo and that calmodulin-dependent kinase II (CaMKII), as well as PKC, catalyzes this reaction in vitro. We find that phosphorylation of myogenin at T87 is dispensable for skeletal muscle development. We show, however, that the decrease in myogenin (myg) expression following innervation is delayed and that the increase in expression following denervation is accelerated in mutant mice lacking phosphorylation of myogenin at T87. These data indicate that two distinct innervation-dependent mechanisms restrain myogenin activity: an inactivation mechanism mediated by phosphorylation of myogenin at T87, and a second, novel regulatory mechanism that regulates myg gene activity independently of T87 phosphorylation.
43
Hughes, S. M., J. M. Taylor, S. J. Tapscott, C. M. Gurley, W. J. Carter, and C. A. Peterson. "Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones." Development 118, no. 4 (August 1, 1993): 1137–47. http://dx.doi.org/10.1242/dev.118.4.1137.
Full textAbstract:
Each of the myogenic helix-loop-helix transcription factors (MyoD, Myogenin, Myf-5, and MRF4) is capable of activating muscle-specific gene expression, yet distinct functions have not been ascribed to the individual proteins. We report here that MyoD and Myogenin mRNAs selectively accumulate in hindlimb muscles of the adult rat that differ in contractile properties: MyoD is prevalent in fast twitch and Myogenin in slow twitch muscles. The distribution of MyoD and Myogenin transcripts also differ within a single muscle and correlate with the proportions of fast glycolytic and slow oxidative muscle fibres, respectively. Furthermore, the expression of a transgene consisting of a muscle-specific cis-regulatory region from the myoD gene controlling lacZ was primarily associated with the fast glycolytic fibres. Alteration of the fast/slow fibre type distribution by thyroid hormone treatment or by cross-reinnervation resulted in a corresponding alteration in the MyoD/Myogenin mRNA expression pattern. These findings show that the expression of specific myogenic helix-loop-helix regulators is under the control of innervation and humoral factors and may mediate differential control of contractile protein gene expression in adult muscle.
44
Ma, Kewei, Jonathan K. L. Chan, Guang Zhu, and Zhenguo Wu. "Myocyte Enhancer Factor 2 Acetylation by p300 Enhances Its DNA Binding Activity, Transcriptional Activity, and Myogenic Differentiation." Molecular and Cellular Biology 25, no. 9 (May 1, 2005): 3575–82. http://dx.doi.org/10.1128/mcb.25.9.3575-3582.2005.
Full textAbstract:
ABSTRACT Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 proteins are known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated by p300 both in vitro and in vivo. In C2C12 myogenic cells, MEF2 is preferentially acetylated in differentiating myocytes but not in undifferentiated myoblasts. Several major acetylation sites are mapped to the transactivation domain of MEF2C, some of which are fully conserved in other MEF2 members from several different species. Mutation of these lysines affects MEF2 DNA binding and transcriptional activity, as well as its synergistic effect with myogenin in myogenic conversion assays. When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation. Thus, in addition to phosphorylation, MEF2 activity is also critically regulated by acetylation during myogenesis.
45
Fox, J. C., A. Y. Hsu, and J. L. Swain. "Myogenic differentiation triggered by antisense acidic fibroblast growth factor RNA." Molecular and Cellular Biology 14, no. 6 (June 1994): 4244–50. http://dx.doi.org/10.1128/mcb.14.6.4244.
Full textAbstract:
Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development.
46
Fox, J. C., A. Y. Hsu, and J. L. Swain. "Myogenic differentiation triggered by antisense acidic fibroblast growth factor RNA." Molecular and Cellular Biology 14, no. 6 (June 1994): 4244–50. http://dx.doi.org/10.1128/mcb.14.6.4244-4250.1994.
Full textAbstract:
Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development.
47
Grabiec, K., J. Tokarska, M. Milewska, M. Błaszczyk, M. Gajewska, and K. Grzelkowska-Kowalczyk. "Interleukin-1β stimulates early myogenesis of mouse C2C12 myoblasts: the impact on myogenic regulatory factors, extracellular matrix components, IGF binding proteins and protein kinases." Polish Journal of Veterinary Sciences 16, no. 2 (June 1, 2013): 255–64. http://dx.doi.org/10.2478/pjvs-2013-0036.
Full textAbstract:
AbstractThe purpose of the study was to examine the mechanisms important for early myogenesis in mouse C2C12 myogenic cells exposed to interleukin-1β. Cyclin A and cyclin B1 were increased by interleukin-1β (1 ng/ml), but the level of cyclin D1 and total DNA content was unaffected. Fusion index and the rate of protein synthesis was increased in the presence of IL-1β, but these effects were limited to 3-day-treatment. IL-1β increased the level of MyoD, myogenin and MHC on the 3rd day of differentiation, without altering the content of the active form of myostatin, as well as it augmented the level of fibronectin, integrin β1 and full length 100 kDa form of ADAM12. IL-1β caused a decrease in IGFBP-4 and IGFBP-6 levels and a marked increase in IGFBP-5. The phosphorylation of PKB and ERK1/2 and the cellular content of p38 were elevated by IL-1β. We conclude that the myogenic effect of IL-1β was limited to the onset of myoblast fusion and was associated with: i) increase in the level of myogenic transcription factors i.e. MyoD and myogenin expression, ii) modification of extracellular matrix assembly and signaling, manifested by an increase in fibronectin, integrin-β1 and ADAM12 content, iii) drop in IGFBP-4 and IGFBP-6, and an increase in IGFBP-5, that could alter the local IGF-1 bioavailability, and iv) increase in phosphorylation of PKB and ERK1/2, and the expression of p38 kinase, leading to activation of intracellular pathways essential for myogenic differentiation.
48
Hoene, Miriam, Heike Runge, Hans Ulrich Häring, Erwin D. Schleicher, and Cora Weigert. "Interleukin-6 promotes myogenic differentiation of mouse skeletal muscle cells: role of the STAT3 pathway." American Journal of Physiology-Cell Physiology 304, no. 2 (January 15, 2013): C128—C136. http://dx.doi.org/10.1152/ajpcell.00025.2012.
Full textAbstract:
Myogenic differentiation of skeletal muscle cells is characterized by a sequence of events that include activation of signal transducer and activator of transcription 3 (STAT3) and enhanced expression of its target gene Socs3. Autocrine effects of IL-6 may contribute to the activation of the STAT3-Socs3 cascade and thus to myogenic differentiation. The importance of IL-6 and STAT3 for the differentiation process was studied in C2C12 cells and in primary mouse wild-type and IL-6−/− skeletal muscle cells. In differentiating C2C12 myoblasts, the upregulation of IL-6 mRNA expression and protein secretion started after increased phosphorylation of STAT3 on tyrosine 705 and increased mRNA expression of Socs3 was observed. Knockdown of STAT3 and IL-6 mRNA in differentiating C2C12 myoblasts impaired the expression of the myogenic markers myogenin and MyHC IIb and subsequently myotube fusion. However, the knockdown of IL-6 did not prevent the induction of STAT3 tyrosine phosphorylation. The IL-6-independent activation of STAT3 was verified in differentiating primary IL-6−/− myoblasts. The phosphorylation of STAT3 and the expression levels of STAT3, Socs3, and myogenin during differentiation were comparable in the primary myoblasts independent of the genotype. However, IL-6−/− cells failed to induce MyHC IIb expression to the same level as in wild-type cells and showed reduced myotube formation. Supplementation of IL-6 could partially restore the fusion of IL-6−/− cells. These data demonstrate that IL-6 depletion during myogenic differentiation does not reduce the activation of the STAT3-Socs3 cascade, while IL-6 and STAT3 are both necessary to promote myotube fusion.
49
Zainul Azlan, Nurhazirah, Yasmin Anum Mohd Yusof, Ekram Alias, and Suzana Makpol. "Chlorella vulgaris Improves the Regenerative Capacity of Young and Senescent Myoblasts and Promotes Muscle Regeneration." Oxidative Medicine and Cellular Longevity 2019 (June 4, 2019): 1–16. http://dx.doi.org/10.1155/2019/3520789.
Full textAbstract:
Sarcopenia is characterized by the loss of muscle mass, strength, and function with ageing. With increasing life expectancy, greater attention has been given to counteracting the effects of sarcopenia on the growing elderly population. Chlorella vulgaris, a microscopic, unicellular, green alga with the potential for various pharmaceutical uses, has been widely studied in this context. This study is aimed at determining the effects of C. vulgaris on promoting muscle regeneration by evaluating myoblast regenerative capacity in vitro. Human skeletal myoblast cells were cultured and underwent serial passaging into young and senescent phases and were then treated with C. vulgaris, followed by the induction of differentiation. The ability of C. vulgaris to promote myoblast differentiation was analysed through cellular morphology, real-time monitoring, cell proliferation, senescence-associated β-galactosidase (SA-β-gal) expression, myogenic differentiation, myogenin expression, and cell cycle profiling. The results obtained showed that senescent myoblasts exhibited an enlarged and flattened morphology, with increased SA-β-gal expression, reduced myogenic differentiation, decreased expression of myogenin, and an increased percentage of cells in the G0/G1 phase. Treatment with C. vulgaris resulted in decreased SA-β-gal expression and promotion of myogenic differentiation, as observed via an increased fusion index, maturation index, myotube size, and surface area and an increased percentage of cells that stained positive for myogenin. In conclusion, C. vulgaris improves the regenerative capacity of young and senescent myoblasts and promotes myoblast differentiation, indicating its potential to promote muscle regeneration.
50
Marsh, Daniel R., David S. Criswell, James A. Carson, and Frank W. Booth. "Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats." Journal of Applied Physiology 83, no. 4 (October 1, 1997): 1270–75. http://dx.doi.org/10.1152/jappl.1997.83.4.1270.
Full textAbstract:
Marsh, Daniel R., David S. Criswell, James A. Carson, and Frank W. Booth. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270–1275, 1997.—Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.