scholarly journals Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis

1993 ◽  
Vol 13 (10) ◽  
pp. 4220-4228 ◽  
Author(s):  
IR Boniece ◽  
JA Wagner
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Pc12 Cells

Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells

2000 ◽  
Vol 347 (2) ◽  
pp. 399-406 ◽  
Author(s):  
Miranda KLEIJN ◽  
Christopher G. PROUD
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Growth Factors ◽  
Pc12 Cells ◽  
Initiation Factor ◽  
S6 Kinase ◽  
Translational Machinery ◽  
Ribosomal Protein S6 ◽  
Eif4f Complex ◽  
Extracellular Regulated Kinase

In PC12 phaeochromocytoma cells, protein synthesis is activated by epidermal and nerve growth factors (EGF and NGF). EGF and NGF also regulate a number of components of the translational machinery in these cells. Here we show that the ability of EGF and NGF to induce the phosphorylation of the 70 kDa ribosomal protein, S6 kinase, and the eukaryotic initiation factor (eIF), 4E-binding protein 1, is dependent upon the presence of amino acids (but not glucose) in the medium. This resembles the regulation of these proteins by insulin, which also requires amino acids. Glucose, but not amino acids, is required for the activation of eIF2B by EGF and NGF. In contrast, EGF and NGF can still activate protein synthesis in the absence of nutrients, suggesting that other regulatory events are important in this. In nutrient-deprived cells, an increase in the phosphorylation of eIF4E, and the assembly of the eIF4F complex by EGF and NGF, coincided with the activation of protein synthesis. In serum-starved cells, activation of protein synthesis, phosphorylation of eIF4E, and formation of the eIF4F complex, were blocked by inhibition of MEK, a component of the extracellular regulated kinase (ERK) signalling pathway. Thus the ERK pathway plays a key role in the regulation of protein synthesis in PC12 cells.

Mechanisms of renal tubular cell hypertrophy: mitogen-induced suppression of proteolysis

1997 ◽  
Vol 273 (3) ◽  
pp. C843-C851 ◽  
Author(s):  
H. A. Franch ◽  
P. V. Curtis ◽  
W. E. Mitch
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Degradation ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Renal Tubular Cell ◽  
Kidney Cells ◽  
Tgf Beta ◽  
Lysosomal Proteolysis

The combination of epidermal growth factor (EGF) plus transforming growth factor-beta 1 (TGF-beta 1) causes hypertrophy in renal epithelial cells. One mechanism contributing to hypertrophy is that EGF induces activation of the cell cycle and increases protein synthesis, whereas TGF-beta 1 prevents cell division, thereby converting hyperplasia to hypertrophy. To assess whether suppression of proteolysis is another mechanism causing hypertrophy induced by these growth factors, we measured protein degradation in primary cultures of proximal tubule cells and in cultured NRK-52E kidney cells. A concentration of 10(-8) M EGF alone or EGF plus 10(-10) M TGF-beta 1 decreased proteolysis by approximately 30%. TGF-beta 1 alone did not change protein degradation. Using inhibitors, we examined which proteolytic pathway is suppressed. Neither proteasome nor calpain inhibitors prevented the antiproteolytic response to EGF + TGF-beta 1. Inhibitors of lysosomal proteases eliminated the antiproteolytic response to EGF + TGF-beta 1, suggesting that these growth factors act to suppress lysosomal proteolysis. This antiproteolytic response was not caused by impaired EGF receptor signaling, since lysosomal inhibitors did not block EGF-induced protein synthesis. We conclude that suppression of lysosomal proteolysis contributes to growth factor-mediated hypertrophy of cultured kidney cells.

scholarly journals Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons.

1992 ◽  
Vol 119 (6) ◽  
pp. 1669-1680 ◽  
Author(s):  
P W Mesner ◽  
T R Winters ◽  
S H Green
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Pc12 Cells ◽  
Sympathetic Neurons ◽  
Nerve Growth ◽  
Neuronal Pc12 Cells ◽  
New Protein

Previous studies have shown that in neuronal cells the developmental phenomenon of programmed cell death is an active process, requiring synthesis of both RNA and protein. This presumably reflects a requirement for novel gene products to effect cell death. It is shown here that the death of nerve growth factor-deprived neuronal PC12 cells occurs at the same rate as that of rat sympathetic neurons and, like rat sympathetic neurons, involves new transcription and translation. In nerve growth factor-deprived neuronal PC12 cells, a decline in metabolic activity, assessed by uptake of [3H]2-deoxyglucose, precedes the decline in cell number, assessed by counts of trypan blue-excluding cells. Both declines are prevented by actinomycin D and anisomycin. In contrast, the death of nonneuronal (chromaffin-like) PC12 cells is not inhibited by transcription or translation inhibitors and thus does not require new protein synthesis. DNA fragmentation by internucleosomal cleavage does not appear to be a consistent or significant aspect of cell death in sympathetic neurons, neuronal PC12 cells, or nonneuronal PC12 cells, notwithstanding that the putative nuclease inhibitor aurintricarboxylic acid protects sympathetic neurons, as well as neuronal and nonneuronal PC12 cells, from death induced by trophic factor removal. Both phenotypic classes of PC12 cells respond to aurintricarboxylic acid with similar dose-response characteristics. Our results indicate that programmed cell death in neuronal PC12 cells, but not in nonneuronal PC12 cells, resembles programmed cell death in sympathetic neurons in significant mechanistic aspects: time course, role of new protein synthesis, and lack of a significant degree of DNA fragmentation.

Differential Effects of Fibroblast Growth Factors on Expression of Genes of the Plasminogen Activator and Insulin-like Growth Factor Systems by Human Breast Fibroblasts

2002 ◽  
Vol 87 (04) ◽  
pp. 674-683 ◽  
Author(s):  
John Martens ◽  
Lambert Dorssers ◽  
Jan Klijn ◽  
John Foekens ◽  
Anieta Sieuwerts
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Plasminogen Activator ◽  
De Novo ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Human Breast ◽  
Short Term ◽  
De Novo Protein Synthesis

SummaryIn breast stroma urokinase plasminogen activator (uPA) is predominantly expressed by fibroblasts located in the near vicinity of tumor cells, and fibroblast-derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the expression of uPA in these fibroblasts. To investigate a possible role for fibroblast growth factors (FGFs), we evaluated the expression of components of the PA system and the IGF system in normal and tumor-tissue-derived human breast fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1, FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA. Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall lagged behind but were longer-lasting. For FGF-4 an in between pattern was observed. Blocking transcription and translation demonstrated that a) both the FGF-1 and FGF-2 induced effects were the result of altered gene transcription or mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not depend on de novo protein synthesis during the first 24 h, but were triggered by proteins produced or made available thereafter. The data presented propose that of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive target for therapeutical strategies aimed at diminishing the contribution of stromal fibroblasts in the PA-directed breast tumor proteolysis.

TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells

2002 ◽  
Vol 283 (4) ◽  
pp. F707-F716 ◽  
Author(s):  
Elizabeth Gore-Hyer ◽  
Daniel Shegogue ◽  
Malgorzata Markiewicz ◽  
Shianlen Lo ◽  
Debra Hazen-Martin ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Potent Inducer ◽  
Collagen Promoter

Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including fibrotic diseases of the kidney. To clarify the common and divergent roles of these growth factors in the cells responsible for pathological extracellular matrix (ECM) deposition in renal fibrosis, the effects of TGF-β and CTGF on ECM expression in primary human mesangial (HMCs) and human proximal tubule epithelial cells (HTECs) were studied. Both TGF-β and CTGF significantly induced collagen protein expression with similar potency in HMCs. Additionally, α2(I)-collagen promoter activity and mRNA levels were similarly induced by TGF-β and CTGF in HMCs. However, only TGF-β stimulated collagenous protein synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF-β and CTGF, although TGF-β was the more potent inducer. Thus both growth factors elicit similar profibrogenic effects on ECM production in HMCs, while promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of epithelial-mesenchymal transdifferentiation (EMT), with no significant induction of collagenous protein synthesis in HTECs, may suggest a more predominant role for CTGF in EMT rather than induction of excessive collagen deposition by HTECs during renal fibrosis.

Gene Transcription of Angiotensin II Type 2 Receptor Is Repressed by Growth Factors and Glucocorticoids in PC12 Cells

1995 ◽  
Vol 216 (1) ◽  
pp. 359-366 ◽  
Author(s):  
K. Kijima ◽  
H. Matsubara ◽  
S. Murasawa ◽  
K. Maruyama ◽  
Y. Mori ◽  
...  
Keyword(s):  
Growth Factors ◽  
Angiotensin Ii ◽  
Pc12 Cells ◽  
Gene Transcription

Protein metabolism in ovine primary muscle cultures derived from satellite cells – effects of selected peptide hormones and growth factors

1989 ◽  
Vol 122 (2) ◽  
pp. 565-571 ◽  
Author(s):  
J. A. Roe ◽  
J. M. M. Harper ◽  
P. J. Buttery
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Satellite Cells ◽  
Specific Activity ◽  
Additive Effect ◽  
Type I ◽  
Igf I ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

ABSTRACT Methods were developed for the isolation and culture of satellite cells from adult sheep muscle. Differentiated cultures of these cells were used to investigate the effects of four hormones and growth factors on protein synthesis and degradation. Insulin was found to have no effect except at supraphysiological concentrations (100 nmol/l and 1 μmol/l) where it is probably cross-reacting with the insulin-like growth factor (IGF) type-I receptor. IGF-I was found to be anabolic at lower concentrations (1–3 nmol/l). Epidermal growth factor (EGF) had a smaller effect on protein synthesis and degradation than insulin or IGF-I. The specific activity of the muscle-specific enzyme creatine phosphokinase (CPK) was increased by treatment with EGF. When both IGF-I and EGF were present in the test media an additive effect on protein synthesis was observed. However, no additive effect of IGF-I and insulin was noted. No effects of bovine GH were seen. Journal of Endocrinology (1989) 122, 565–571

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