The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable

1988 ◽  
Vol 127 (2) ◽  
pp. 316-325 ◽  
Author(s):  
Reuven Stein ◽  
Sigmond Orit ◽  
David J. Anderson
Keyword(s):  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Specific Gene ◽  
Nerve Growth

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.

Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription

1986 ◽  
Vol 6 (4) ◽  
pp. 1050-1057
Author(s):  
M E Greenberg ◽  
A L Hermanowski ◽  
E B Ziff
Keyword(s):  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Gene Transcription ◽  
Actin Gene ◽  
Mrna Levels ◽  
Protein Synthesis Inhibitors ◽  
3T3 Cells ◽  
Nerve Growth

Stimulation of quiescent 3T3 cells with purified growth factors or of the pheochromocytoma cell line PC12 with nerve growth factor results in the rapid transient induction of c-fos, c-myc, and actin gene transcription (M.E. Greenberg and E.B. Ziff, Nature [London] 312:711-716; M.E. Greenberg, L.A. Greene, and E.B. Ziff, J. Biol. Chem. 26:14101-14110). We used protein synthesis inhibitors to investigate whether synthesis of new proteins plays a role in the rapid induction and subsequent repression of the transcription of these genes. Pretreatment of quiescent 3T3 cells with the inhibitor anisomycin before growth factor stimulation caused a superinduction of c-fos and c-myc mRNA levels upon growth factor addition. Nuclear runoff transcription analyses of 3T3 cells indicated that anisomycin potentiated c-fos, c-myc, and also actin expression at the transcriptional level, possibly by inhibiting transcriptional repression. Somewhat different results were obtained when PC12 cells were incubated with either anisomycin or cycloheximide. In PC12 cells protein synthesis inhibitors superinduced nerve growth factor activation of c-fos mRNA production but completely abolished the activation of c-myc. The results suggest that in PC12 cells c-fos transcription is activated by a protein-synthesis-independent mechanism, whereas c-myc stimulation requires new protein synthesis. The difference in the effect of anisomycin on growth factor activation of c-myc expression in 3T3 versus PC12 cells may be due to differential stringency of protein synthesis inhibition in the two cells or could reflect cell type differences in c-myc regulation.

scholarly journals eIF4F complex disruption causes protein synthesis inhibition during hypoxia in nerve growth factor (NGF)-differentiated PC12 cells

2012 ◽  
Vol 1823 (2) ◽  
pp. 430-438 ◽  
Author(s):  
Macarena Hernández-Jiménez ◽  
M. Irene Ayuso ◽  
M. Isabel Pérez-Morgado ◽  
Eva M. García-Recio ◽  
Alberto Alcázar ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Protein Synthesis Inhibition ◽  
Nerve Growth ◽  
Synthesis Inhibition ◽  
Differentiated Pc12 Cells ◽  
Eif4f Complex

scholarly journals Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription.

1986 ◽  
Vol 6 (4) ◽  
pp. 1050-1057 ◽  
Author(s):  
M E Greenberg ◽  
A L Hermanowski ◽  
E B Ziff
Keyword(s):  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Gene Transcription ◽  
Actin Gene ◽  
Mrna Levels ◽  
Protein Synthesis Inhibitors ◽  
3T3 Cells ◽  
Nerve Growth

Stimulation of quiescent 3T3 cells with purified growth factors or of the pheochromocytoma cell line PC12 with nerve growth factor results in the rapid transient induction of c-fos, c-myc, and actin gene transcription (M.E. Greenberg and E.B. Ziff, Nature [London] 312:711-716; M.E. Greenberg, L.A. Greene, and E.B. Ziff, J. Biol. Chem. 26:14101-14110). We used protein synthesis inhibitors to investigate whether synthesis of new proteins plays a role in the rapid induction and subsequent repression of the transcription of these genes. Pretreatment of quiescent 3T3 cells with the inhibitor anisomycin before growth factor stimulation caused a superinduction of c-fos and c-myc mRNA levels upon growth factor addition. Nuclear runoff transcription analyses of 3T3 cells indicated that anisomycin potentiated c-fos, c-myc, and also actin expression at the transcriptional level, possibly by inhibiting transcriptional repression. Somewhat different results were obtained when PC12 cells were incubated with either anisomycin or cycloheximide. In PC12 cells protein synthesis inhibitors superinduced nerve growth factor activation of c-fos mRNA production but completely abolished the activation of c-myc. The results suggest that in PC12 cells c-fos transcription is activated by a protein-synthesis-independent mechanism, whereas c-myc stimulation requires new protein synthesis. The difference in the effect of anisomycin on growth factor activation of c-myc expression in 3T3 versus PC12 cells may be due to differential stringency of protein synthesis inhibition in the two cells or could reflect cell type differences in c-myc regulation.

scholarly journals Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells.

1988 ◽  
Vol 106 (5) ◽  
pp. 1583-1591 ◽  
Author(s):  
D Drubin ◽  
S Kobayashi ◽  
D Kellogg ◽  
M Kirschner
Keyword(s):  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Feedback Regulation ◽  
The State ◽  
Mrna Levels ◽  
Microtubule Depolymerization ◽  
Nerve Growth ◽  
Microtubule Polymerization

Nerve growth factor induces neurite process formation in pheochromacytoma (PC12) cells and causes the parallel increase in levels of the microtubule-associated proteins, tau and MAP1, as well as increases in tubulin levels. Mechanisms to insure balanced accumulation of microtubule proteins and make their levels highly responsive to nerve growth factor were investigated. The effects on tau, MAP1, and tubulin are due to changes in protein synthesis rates, which for tau and tubulin we could show are due in part to changes in the mRNA levels. Whereas tubulin shows feedback regulation to modulate synthesis up or down, tau protein synthesis is not affected in a straightforward way by microtubule polymerization and depolymerization. The degradation of tau, MAP1, and both tubulin polypeptides, however, are stimulated by microtubule depolymerization caused by colchicine, or nerve growth factor removal. Combined feedback on synthesis and stability make tubulin levels highly responsive to assembly states. In addition, the linkage of tau and MAP1 turnover with the state of microtubule polymerization amplifies any change in their rate of synthesis, since tau and MAP1 promote microtubule polymerization. This linkage lends itself to rapid changes in the state of the system in response to nerve growth factor.

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