Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity

2006 ◽  
Vol 291 (4) ◽  
pp. C699-C709 ◽  
Author(s):  
David Kuninger ◽  
Alistair Wright ◽  
Peter Rotwein
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Muscle Development ◽  
Acetyltransferase Activity ◽  
Skeletal Myoblasts ◽  
Transcriptional Coactivators ◽  
Peptide Growth Factors ◽  
Promote Cell Survival ◽  
Conditioned Culture Medium

Normal skeletal muscle development requires the proper orchestration of genetic programs by myogenic regulatory factors (MRFs). The actions of the MRF protein MyoD are enhanced by the transcriptional coactivators p300 and the p300/CBP-associated factor (PCAF). We previously described C2 skeletal myoblasts lacking expression of insulin-like growth factor-II (IGF-II) that underwent progressive apoptotic death when incubated in differentiation-promoting medium. Viability of these cells was sustained by addition of IGF analogs or unrelated peptide growth factors. We now show that p300 or PCAF maintains myoblast viability as effectively as added growth factors through mechanisms requiring the acetyltransferase activity of PCAF but not of p300. The actions of p300 to promote cell survival were not secondary to increased expression of known MyoD targets, as evidenced by results of gene microarray experiments, but rather appeared to be mediated by induction of other genes, including fibroblast growth factor-1 (FGF-1). Conditioned culture medium from cells expressing p300 increased myoblast viability, and this was blocked by pharmacological inhibition of FGF receptors. Our results define a role for p300 in promoting cell survival, which is independent of its acetyltransferase activity and acts at least in part through FGF-1.

scholarly journals Zinc and Copper with New Triazine Hydrazone Ligand: Two Novel Organic Complexes Enhanced Expression of Peptide Growth Factors and Cytokine Genes in Weaned V-Line Rabbit

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1134 ◽  
Author(s):  
Elokil ◽  
Imbabi ◽  
Mohamed ◽  
Abouelezz ◽  
Ahmed-Farid ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Intestinal Morphology ◽  
Saline Control ◽  
Hydrazone Ligand ◽  
Carcass Yield ◽  
Cytokine Genes ◽  
Organic Complexes ◽  
Peptide Growth Factors

Two novel transitional organic Zn/Cu complexes based on a new biocompatible bidentate triazine–hydrazone ligand (Thz) was designed, synthesized, and evaluated in this study. This study evaluated the effects of injecting 60 mg of Zn and 40 mg of Cu in three different forms, twice per week, for eight weeks on growth performance, expression of growth factors and cytokine genes, carcass yield, blood biochemicals, and intestinal morphology in weaned rabbits. The tested complexes were sulfate (Cu/ZnSO4), montmorillonite (Cu/Zn-Mnt), and triazine hydrazone (Cu/Zn-Thz). A total of 60 V-line weaned rabbits at four weeks of age were assigned to four treatments (n = 15), which were intramuscularly injected with 0.5 mL of either (1) saline (control) or saline containing (2) Cu/ZnSO4, (3) Cu/Zn-Mnt, or (4) Cu/Zn-Thz. Compared to the controls, the rabbits injected with Cu/Zn-Thz showed a higher (p < 0.01) growth rate, carcass yield (p < 0.05), and liver expression of insulin like growth factor-1 (IGF-1), growth hormone receptor (GHR), fibroblast growth factor-1 (FGF1), and transforming growth factor beta-1 (TGFB1) (p < 0.05), as well as better jejunum morphometric variables (p < 0.05). On the other hand, mRNA of FGF1, TGF1, TCIRG1, and adenosine deaminase (ADA) were higher expressed (p < 0.05) in the spleen tissues of Cu/Zn-Mnt group. Collectively, the results indicated that our novel synthesized organic complexes of Zn/Cu-Thz proved to be a suitable feed supplement, as it increased rabbit productive performance through enhancing expression of peptide growth factors and cytokine genes.

Apoptosis in the haemopoietic system

1994 ◽  
Vol 345 (1313) ◽  
pp. 257-263 ◽  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Lineage Differentiation ◽  
Haemopoietic Stem Cells ◽  
Underlying Causes ◽  
Membrane Bound ◽  
Survival Signals

Our previous studies have shown that haemopoietic stem cells undergo apoptotic death as a consequence of growth factor withdrawal. In this paper we review the new data that has accumulated since this observation and compare it with older data from the ‘pre-apoptotic’ age. Models of erythropoiesis and granulopoiesis that incorporate apoptosis as a normal physiological process controlling homeostasis are examined. The converse to cell death is cell survival, and we describe experiments which suggest that haemopoietic growth factors can not only act as mitogenic or differentiation stimuli but also act as survival signals. We, and others, have proposed that these growth factor-induced survival signals act through the membrane bound polypeptide receptors and share common features of signal transduction with proliferative responses. Enforced expression of bcl-2 in haemopoietic stem cells is able to overcome apoptosis following the withdrawal of growth factor, and the cells commit into different lineage differentiation programmes. Such cells spontaneously differentiate without cell division, suggesting a stochastic model of haemopoiesis in which the major role of haemopoietic growth factors is to suppress apoptosis and act as mitogens. We review the evidence that the underlying causes of some haematological diseases may be associated with change in the balance between cell survival and death.

scholarly journals Neuroprotection by Peptide Growth Factors against Anoxia and Nitric Oxide Toxicity Requires Modulation of Protein Kinase C

1995 ◽  
Vol 15 (3) ◽  
pp. 440-449 ◽  
Author(s):  
Kenneth Maiese ◽  
Lauraine Boccone
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Neuronal Degeneration ◽  
Kinase C ◽  
Peptide Growth Factors ◽  
Pkc Activation

Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) are neuroprotective during anoxia and nitric oxide (NO) toxicity. Signal transduction systems that modulate protein kinase C (PKC) also can modulate the toxic effects of anoxia and NO. We therefore examined whether PKC was involved in the protective effects of bFGF and EGF during anoxia and NO toxicity. Down-regulation or inhibition of PKC activity before anoxia or NO exposure prevented hippocampal neuronal degeneration. Yet, this protective effect of inhibition of PKC activity was not present with the coadministration of growth factors. Combined inhibition of PKC activity and application of bFGF or EGF lessened the protective mechanisms of the growth factors. In addition, the protective ability of the growth factors was lost during anoxia and NO exposure with the activation of PKC, suggesting that at least a minimal degree of PKC activation is necessary for growth factor protection. Although modulation of PKC activity may be a necessary prerequisite for protection against anoxia and NO toxicity by bFGF and EGF, only inhibition of PKC activity, rather than application of the growth factors, was protective following exposure to NO. These results suggest that the mechanism of protection by bFGF and EGF during anoxia and NO toxicity appears initially to be dependent on a minimum degree of PKC activation, but that other signal transduction pathways independent of PKC also may mediate protection by peptide growth factors.

scholarly journals Basic fibroblast growth factor in the chick embryo: immunolocalization to striated muscle cells and their precursors.

1989 ◽  
Vol 108 (6) ◽  
pp. 2459-2466 ◽  
Author(s):  
J Joseph-Silverstein ◽  
S A Consigli ◽  
K M Lyser ◽  
C Ver Pault
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Chick Embryo ◽  
Muscle Development ◽  
Striated Muscle ◽  
Muscle Cells ◽  
Limb Bud ◽  
Fibroblast Growth ◽  
Lack Of Information ◽  
Immunohistochemical Techniques

The identification of acidic and basic fibroblast growth factors (FGFs) in a number of embryonic tissue extracts has implicated these growth factors in the regulation of a variety of embryonic events including angiogenesis, eye development, and muscle differentiation. Lack of information concerning the cellular distribution of the growth factor within these tissues has made it extremely difficult to assign developmental roles to FGF. We have localized bFGF in the developing chick embryo using immunohistochemical techniques and our monospecific polyclonal rabbit anti-human bFGF IgG. The spatial pattern for bFGF localization was highly specific. The anti-human bFGF antibodies recognized striated muscle cells and their precursors in 2-6-d chick embryos. Myocardium, somite myotome, and limb bud muscle all stain positively for bFGF. In addition, the anti-human bFGF antibodies localized specifically to the cell, rather than to the extracellular matrix or nucleus of myotubes. The localization of bFGF demonstrated here provides further support for the hypothesis (Clegg et al., 1987; Seed et al., 1988) that this growth factor is involved in muscle development.

scholarly journals Dual Control of Muscle Cell Survival by Distinct Growth Factor-Regulated Signaling Pathways

2000 ◽  
Vol 20 (9) ◽  
pp. 3256-3265 ◽  
Author(s):  
Margaret A. Lawlor ◽  
Xiuhong Feng ◽  
Daniel R. Everding ◽  
Kerry Sieger ◽  
Claire E. H. Stewart ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Signaling Pathways ◽  
Muscle Cell ◽  
Transient Transfection ◽  
Pi3 Kinase ◽  
Signal Transduction Pathways ◽  
Apoptotic Death ◽  
Igf I

ABSTRACT In addition to their ability to stimulate cell proliferation, polypeptide growth factors are able to maintain cell survival under conditions that otherwise lead to apoptotic death. Growth factors control cell viability through regulation of critical intracellular signal transduction pathways. We previously characterized C2 muscle cell lines that lacked endogenous expression of insulin-like growth factor II (IGF-II). These cells did not differentiate but underwent apoptotic death in low-serum differentiation medium. Death could be prevented by IGF analogues that activated the IGF-I receptor or by unrelated growth factors such as platelet-derived growth factor BB (PDGF-BB). Here we analyze the signaling pathways involved in growth factor-mediated myoblast survival. PDGF treatment caused sustained activation of extracellular-regulated kinases 1 and 2 (ERK1 and -2), while IGF-I only transiently induced these enzymes. Transient transfection of a constitutively active Mek1, a specific upstream activator of ERKs, maintained myoblast viability in the absence of growth factors, while inhibition of Mek1 by the drug UO126 blocked PDGF-mediated but not IGF-stimulated survival. Although both growth factors activated phosphatidylinositol 3-kinase (PI3-kinase) to similar extents, only IGF-I treatment led to sustained stimulation of its downstream kinase, Akt. Transient transfection of a constitutively active PI3-kinase or an inducible Akt promoted myoblast viability in the absence of growth factors, while inhibition of PI3-kinase activity by the drug LY294002 selectively blocked IGF- but not PDGF-mediated muscle cell survival. In aggregate, these observations demonstrate that distinct growth factor-regulated signaling pathways independently control myoblast survival. Since IGF action also stimulates muscle differentiation, these results suggest a means to regulate myogenesis through selective manipulation of different signal transduction pathways.

Oligodendrocytes and their precursors require phosphatidylinositol 3-kinase signaling for survival

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2529-2537
Author(s):  
G.S. Vemuri ◽  
F.A. McMorris
Keyword(s):  
Cell Death ◽  
Enzyme Activity ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Nuclear Dna ◽  
Apoptotic Cell ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Signal transduction in response to several growth factors that regulate oligodendrocyte development and survival involves the activation of phosphatidylinositol 3-kinase, which we detect in oligodendrocytes and their precursors. To investigate the role of this enzyme activity, we analyzed cell survival in cultures of oligodendrocytes treated with wortmannin or LY294002, two potent inhibitors of phosphatidylinositol 3-kinase. Cell survival was inhibited by 60–70% in these cultures within 24 hours, as quantitated by a tetrazolium staining assay for viable cells and by measurement of DNA content. Similar results were obtained with oligodendrocyte precursor cells. Nuclei of the dying cells contained fragmented DNA, as revealed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays, indicating that the cells were dying by apoptosis. Moreover, a significant increase in the number of cells with fragmented nuclear DNA was detected as early as 4 hours, well before any significant differences could be detected in glucose transport or cell viability. Exogenous addition of insulin-like growth factor-I, neurotrophin-3, platelet-derived growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, N-acetyl cysteine, vitamin C, vitamin E, progesterone or serum did not prevent cell death in the presence of wortmannin or LY294002. These findings indicate that survival of oligodendrocytes and their precursors depends on a phosphatidylinositol 3-kinase mediated signaling pathway. Inhibition of this critical enzyme activity induces apoptotic cell death, even in the presence of exogenous growth factors or serum.

Growth factors regulate cell survival by controlling nutrient transporter expression

2005 ◽  
Vol 33 (1) ◽  
pp. 225-227 ◽  
Author(s):  
A.L. Edinger
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Chemotherapeutic Agents ◽  
Tumour Suppressor ◽  
Nutrient Transporters ◽  
Nutrient Transporter ◽  
Transporter Expression

Growth factors provide permission signals that allow mammalian cells to grow, proliferate and survive. One mechanism by which growth factors maintain this control is through the regulation of cell surface nutrient transporter expression. Following growth factor withdrawal, nutrient transporters are endocytosed and degraded in the lysosome, effectively terminating the cell's ability to obtain nutrients. This results in a state of pseudostarvation in which cells atrophy and initiate a catabolic metabolic programme in the midst of abundant extracellular nutrients. Oncogenic forms of Akt can support growth factor-independent nutrient transporter expression through a mechanism that depends upon mTOR (mammalian target of rapamycin). The ability of activated Akt to support nutrient transporter expression is an essential component of its prosurvival function. When the destruction of nutrient transporters is inhibited, cells are capable of long-term growth-factor-independent cell survival in the absence of receptor-dependent signal transduction. These results imply that proteins involved in nutrient transporter turnover in response to growth factor withdrawal are components of a novel tumour suppressor pathway. Preliminary data suggest that Rab7, a GTPase required for transporter degradation, functions as a tumour suppressor protein, as inhibiting Rab7 activity promotes colony formation in soft agar. These studies indicate that drugs affecting this pathway might have utility as anti-cancer chemotherapeutic agents.

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