scholarly journals A pRb-independent mechanism preserves the postmitotic state in terminally differentiated skeletal muscle cells

2004 ◽  
Vol 167 (3) ◽  
pp. 417-423 ◽  
Author(s):  
Grazia Camarda ◽  
Francesca Siepi ◽  
Deborah Pajalunga ◽  
Camilla Bernardini ◽  
Rossella Rossi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Synthesis ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Conditional Knockout ◽  
Skeletal Muscle Cells ◽  
Specific Gene ◽  
Pocket Protein ◽  
Independent Mechanism ◽  
Optimal Implementation

In skeletal muscle differentiation, the retinoblastoma protein (pRb) is absolutely necessary to establish definitive mitotic arrest. It is widely assumed that pRb is equally essential to sustain the postmitotic state, but this contention has never been tested. Here, we show that terminal proliferation arrest is maintained in skeletal muscle cells by a pRb-independent mechanism. Acute Rb excision from conditional knockout myotubes caused reexpression of E2F transcriptional activity, cyclin-E and -A kinase activities, PCNA, DNA ligase I, RPA, and MCM2, but did not induce DNA synthesis, showing that pRb is not indispensable to preserve the postmitotic state of these cells. Muscle-specific gene expression was significantly down-regulated, showing that pRb is constantly required for optimal implementation of the muscle differentiation program. Rb-deleted myotubes were efficiently reactivated by forced expression of cyclin D1 and Cdk4, indicating a functionally significant target other than pRb for these molecules. Finally, Rb removal induced no DNA synthesis even in pocket-protein null cells. Thus, the postmitotic state of myotubes is maintained by at least two mechanisms, one of which is pocket-protein independent.

scholarly journals Oncogenic Ras-Induced Proliferation Requires Autocrine Fibroblast Growth Factor 2 Signaling in Skeletal Muscle Cells

2001 ◽  
Vol 152 (6) ◽  
pp. 1301-1306 ◽  
Author(s):  
Yuri V. Fedorov ◽  
R. Scott Rosenthal ◽  
Bradley B. Olwin
Keyword(s):  
Skeletal Muscle ◽  
Ectopic Expression ◽  
Terminal Differentiation ◽  
Biological Response ◽  
Muscle Cells ◽  
Sodium Chlorate ◽  
Skeletal Muscle Cells ◽  
Specific Gene ◽  
Fibroblast Growth ◽  
Oncogenic Ras

Constitutively activated Ras proteins are associated with a large number of human cancers, including those originating from skeletal muscle tissue. In this study, we show that ectopic expression of oncogenic Ras stimulates proliferation of the MM14 skeletal muscle satellite cell line in the absence of exogenously added fibroblast growth factors (FGFs). MM14 cells express FGF-1, -2, -6, and -7 and produce FGF protein, yet they are dependent on exogenously supplied FGFs to both maintain proliferation and repress terminal differentiation. Thus, the FGFs produced by these cells are either inaccessible or inactive, since the endogenous FGFs elicit no detectable biological response. Oncogenic Ras-induced proliferation is abolished by addition of an anti–FGF-2 blocking antibody, suramin, or treatment with either sodium chlorate or heparitinase, demonstrating an autocrine requirement for FGF-2. Oncogenic Ras does not appear to alter cellular export rates of FGF-2, which does not possess an NH2-terminal or internal signal peptide. However, oncogenic Ras does appear to be involved in releasing or activating inactive, extracellularly sequestered FGF-2. Surprisingly, inhibiting the autocrine FGF-2 required for proliferation has no effect on oncogenic Ras-mediated repression of muscle-specific gene expression. We conclude that oncogenic Ras-induced proliferation of skeletal muscle cells is mediated via a unique and novel mechanism that is distinct from Ras-induced repression of terminal differentiation and involves activation of extracellularly localized, inactive FGF-2.

scholarly journals Erratum to: Ranolazine promotes muscle differentiation and reduces oxidative stress in C2C12 skeletal muscle cells

Endocrine ◽  
2017 ◽  
Vol 58 (1) ◽  
pp. 46-46 ◽  
Author(s):  
Ileana Terruzzi ◽  
Anna Montesano ◽  
Pamela Senesi ◽  
Fernanda Vacante ◽  
Stefano Benedini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Skeletal Muscle Cells ◽  
C2c12 Skeletal Muscle Cells

scholarly journals Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression.

1993 ◽  
Vol 121 (4) ◽  
pp. 785-793 ◽  
Author(s):  
D P Jasmer
Keyword(s):  
Skeletal Muscle ◽  
Infected Cell ◽  
Dna Synthesis ◽  
Post Infection ◽  
Trichinella Spiralis ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cell Phenotype ◽  
Thymidine Uptake ◽  
Normal Muscle

Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of approximately 4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to < 1- < 0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to < 10, < 1, and increased approximately 250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype.

scholarly journals The FGF Receptor–1 Tyrosine Kinase Domain Regulates Myogenesis but Is Not Sufficient to Stimulate Proliferation

1998 ◽  
Vol 142 (1) ◽  
pp. 241-250 ◽  
Author(s):  
Arthur J. Kudla ◽  
Nathan C. Jones ◽  
R. Scott Rosenthal ◽  
Kirstin Arthur ◽  
Kari L. Clase ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tyrosine Kinase ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Kinase Domain ◽  
Skeletal Muscle Cells ◽  
Tyrosine Kinase Domain ◽  
Protein Kinase Activity ◽  
Skeletal Muscle Differentiation ◽  
Chimeric Receptors

Ligand-stimulated activation of FGF receptors (FGFRs) in skeletal muscle cells represses terminal myogenic differentiation. Skeletal muscle cell lines and subsets of primary cells are dependent on FGFs to repress myogenesis and maintain growth. To understand the intracellular events that transduce these signals, MM14 skeletal muscle cells were transfected with expression vectors encoding chimeric receptors. The chimeras are comprised of the PDGF β receptor (PDGFβR) extracellular domain, the FGFR-1 intracellular domain, and either the PDGFβR or FGFR-1 transmembrane domain. The chimeric receptors were autophosphorylated upon PDGF-BB stimulation and are capable of stimulating mitogen-activated protein kinase activity. Activation of the tyrosine kinase domain of either chimera repressed myogenesis, suggesting intracellular responses regulating skeletal muscle differentiation are transduced by activation of the FGFR-1 tyrosine kinase. Unexpectedly, we found that activation of either chimeric receptor failed to stimulate cellular proliferation. Thus, it appears that regulation of skeletal muscle differentiation by FGFs requires only activation of the FGFR tyrosine kinase. In contrast, stimulation of proliferation may require additional, as yet unidentified, signals involving the receptor ectodomain, the FGF ligand, and heparan sulfate either alone, or in combination.

scholarly journals Ranolazine promotes muscle differentiation and reduces oxidative stress in C2C12 skeletal muscle cells

Endocrine ◽  
2016 ◽  
Vol 58 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Terruzzi Ileana ◽  
Montesano Anna ◽  
Senesi Pamela ◽  
Vacante Fernanda ◽  
Benedini Stefano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Skeletal Muscle Cells ◽  
C2c12 Skeletal Muscle Cells

scholarly journals tk Enzyme expression in differentiating muscle cells is regulated through an internal segment of the cellular tk gene.

1984 ◽  
Vol 4 (9) ◽  
pp. 1777-1784 ◽  
Author(s):  
G F Merrill ◽  
S D Hauschka ◽  
S L McKnight
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Thymidine Kinase ◽  
Terminal Differentiation ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Skeletal Muscle Cells ◽  
Deficient Mouse ◽  
Enzyme Expression

Thymidine kinase (tk) enzyme expression is shut down when cultured skeletal muscle cells terminally differentiate. This regulation is mediated by a rapid and specific decline in the abundance of cellular tk mRNA. tk-deficient mouse myoblasts were transformed to the tk-positive phenotype by using both the cellular tk gene of the chicken and the herpesvirus tk gene. Myoblasts transformed with the cellular tk gene effectively regulate tk enzyme activity upon terminal differentiation. Conversely, myoblasts transformed with the herpesvirus tk gene continue to express tk enzyme activity in postreplicative muscle cells. A regulated pattern of expression is retained when the promoter of the cellular tk gene is replaced by the promoter of the herpesvirus tk gene. Moreover, the cellular tk gene is appropriately regulated during terminal muscle differentiation when its 3' terminus is removed and replaced by the terminus of the viral tk gene. Thus, the element of the cellular tk gene sufficient to specify its regulation is entirely intragenic.

tk Enzyme expression in differentiating muscle cells is regulated through an internal segment of the cellular tk gene

1984 ◽  
Vol 4 (9) ◽  
pp. 1777-1784
Author(s):  
G F Merrill ◽  
S D Hauschka ◽  
S L McKnight
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Thymidine Kinase ◽  
Terminal Differentiation ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Skeletal Muscle Cells ◽  
Deficient Mouse ◽  
Enzyme Expression

Thymidine kinase (tk) enzyme expression is shut down when cultured skeletal muscle cells terminally differentiate. This regulation is mediated by a rapid and specific decline in the abundance of cellular tk mRNA. tk-deficient mouse myoblasts were transformed to the tk-positive phenotype by using both the cellular tk gene of the chicken and the herpesvirus tk gene. Myoblasts transformed with the cellular tk gene effectively regulate tk enzyme activity upon terminal differentiation. Conversely, myoblasts transformed with the herpesvirus tk gene continue to express tk enzyme activity in postreplicative muscle cells. A regulated pattern of expression is retained when the promoter of the cellular tk gene is replaced by the promoter of the herpesvirus tk gene. Moreover, the cellular tk gene is appropriately regulated during terminal muscle differentiation when its 3' terminus is removed and replaced by the terminus of the viral tk gene. Thus, the element of the cellular tk gene sufficient to specify its regulation is entirely intragenic.

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