Nerve growth factor regulates gene expression by several distinct mechanisms

1989 ◽  
Vol 9 (1) ◽  
pp. 135-143
Author(s):  
K O Cho ◽  
W C Skarnes ◽  
B Minsk ◽  
S Palmieri ◽  
L Jackson-Grusby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cholera Toxin ◽  
Phorbol Myristate Acetate ◽  
Kinase Inhibitor ◽  
Transcriptional Level ◽  
Myristate Acetate ◽  
Nerve Growth

To help elucidate the mechanisms by which nerve growth factor (NGF) regulates gene expression, we have identified and studied four genes (a-2, d-2, d-4, and d-5) that are positively regulated by NGF in PC12 cells, including one (d-2) which has previously been identified as a putative transcription factor (NGF I-A). Three of these genes, including d-2, were induced very rapidly at the transcriptional level, but the relative time courses of transcription and mRNA accumulation of each of these three genes were distinct. The fourth gene (d-4) displayed no apparent increase in transcription that corresponded to the increase in its mRNA, suggesting that NGF may regulate its expression at a posttranscriptional level. Thus, NGF positively regulates gene expression by more than one mechanism. These genes could also be distinguished on the basis of their response to cyclic AMP. The expression of d-2 and a-2 was increased by cholera toxin and further augmented by NGF; however, cholera toxin not only failed to increase the levels of d-5 and d-4 mRNA but also actually inhibited the NGF-dependent increase. The expression of each of these genes, including d-2 (NGF I-A), was also increased by fibroblast growth factor, epidermal growth factor (EGF), phorbol myristate acetate, and in some cases insulin, showing that the regulation of these genes is not unique to NGF. Because each of these genes was expressed in response to phorbol myristate acetate and EGF, their expression may be necessary but is certainly not sufficient for neurite formation. The protein kinase inhibitor K-252a prevented the NGF-associated, but not the acidic FGF-associated, induction of d-2 and d-5 gene expression, suggesting that these two growth factors may regulate gene expression via different cellular pathways. The study of the regulation of the expression of these and other NGF-inducible genes should valuable new information concerning how NGF and other growth factors cause neural differentiation.

scholarly journals Nerve growth factor regulates gene expression by several distinct mechanisms.

1989 ◽  
Vol 9 (1) ◽  
pp. 135-143 ◽  
Author(s):  
K O Cho ◽  
W C Skarnes ◽  
B Minsk ◽  
S Palmieri ◽  
L Jackson-Grusby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cholera Toxin ◽  
Phorbol Myristate Acetate ◽  
Kinase Inhibitor ◽  
Transcriptional Level ◽  
Myristate Acetate ◽  
Nerve Growth

To help elucidate the mechanisms by which nerve growth factor (NGF) regulates gene expression, we have identified and studied four genes (a-2, d-2, d-4, and d-5) that are positively regulated by NGF in PC12 cells, including one (d-2) which has previously been identified as a putative transcription factor (NGF I-A). Three of these genes, including d-2, were induced very rapidly at the transcriptional level, but the relative time courses of transcription and mRNA accumulation of each of these three genes were distinct. The fourth gene (d-4) displayed no apparent increase in transcription that corresponded to the increase in its mRNA, suggesting that NGF may regulate its expression at a posttranscriptional level. Thus, NGF positively regulates gene expression by more than one mechanism. These genes could also be distinguished on the basis of their response to cyclic AMP. The expression of d-2 and a-2 was increased by cholera toxin and further augmented by NGF; however, cholera toxin not only failed to increase the levels of d-5 and d-4 mRNA but also actually inhibited the NGF-dependent increase. The expression of each of these genes, including d-2 (NGF I-A), was also increased by fibroblast growth factor, epidermal growth factor (EGF), phorbol myristate acetate, and in some cases insulin, showing that the regulation of these genes is not unique to NGF. Because each of these genes was expressed in response to phorbol myristate acetate and EGF, their expression may be necessary but is certainly not sufficient for neurite formation. The protein kinase inhibitor K-252a prevented the NGF-associated, but not the acidic FGF-associated, induction of d-2 and d-5 gene expression, suggesting that these two growth factors may regulate gene expression via different cellular pathways. The study of the regulation of the expression of these and other NGF-inducible genes should valuable new information concerning how NGF and other growth factors cause neural differentiation.

scholarly journals Regulation of nerve growth factor receptor gene expression by nerve growth factor in the developing peripheral nervous system.

1991 ◽  
Vol 112 (2) ◽  
pp. 303-312 ◽  
Author(s):  
F D Miller ◽  
T C Mathew ◽  
J G Toma
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Receptor Gene ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Nerve Growth ◽  
Receptor Mrna ◽  
Ngf Receptor ◽  
Receptor Gene Expression

Nerve growth factor (NGF) is a target-derived neurotrophic protein that promotes the survival and growth of developing sympathetic and sensory neurons. We have examined NGF receptor gene expression in these neurons after NGF administration. Northern blot and in situ hybridization analyses demonstrated that NGF given systemically to neonatal rats increased levels of NGF receptor mRNA in sympathetic neurons within the superior cervical ganglion. This increase was accompanied by a differential regulation of genes associated with neurotransmitter phenotype; tyrosine hydroxylase mRNA was increased, but neuropeptide Y mRNA was not. NGF receptor mRNA levels were also increased in L4-L5 dorsal root ganglia, although this mRNA was not expressed uniformly in sensory neurons of control or NGF-treated animals. Levels of T alpha 1 alpha-tubulin mRNA, a marker of neuronal growth, also increased. In contrast to developing neurons, systemic NGF did not increase NGF receptor mRNA in nonneuronal cells of the sciatic nerve. To determine if NGF regulated NGF receptor gene expression at the transcriptional level, we examined PC12 cells. NGF treatment for 6 h increased NGF receptor mRNA fourfold; this increase was inhibited by cycloheximide. Nuclear run-off transcription assays demonstrated that the increase in steady-state NGF receptor mRNA levels was mediated at the transcriptional level. In contrast, although NGF treatment increased steady-state tyrosine hydroxylase mRNA levels, this effect was not blocked by cycloheximide, and was not due to increased transcription. These data raise the possibility that transcriptional regulation of NGF receptor gene expression by target-derived NGF could be a molecular mechanism for potentiating NGF's effects on neurons during developmental periods of neuronal competition and cell death.

scholarly journals Pro-Nerve Growth Factor Induces Activation of RhoA Kinase and Neuronal Cell Death

2019 ◽  
Vol 9 (8) ◽  
pp. 204 ◽  
Author(s):  
Marina Sycheva ◽  
Jake Sustarich ◽  
Yuxian Zhang ◽  
Vaithinathan Selvaraju ◽  
Thangiah Geetha ◽  
...  
Keyword(s):  
Cell Death ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Neuronal Cell Death ◽  
Rho Kinase ◽  
Neuronal Cell ◽  
Nerve Growth ◽  
Rhoa Kinase

We have previously shown that the expression of pro-nerve growth factor (proNGF) was significantly increased, nerve growth factor (NGF) level was decreased, and the expression of p75NTR was enhanced in Alzheimer’s disease (AD) hippocampal samples. NGF regulates cell survival and differentiation by binding TrkA and p75NTR receptors. ProNGF is the precursor form of NGF, binds to p75NTR, and induces cell apoptosis. The objective of this study is to determine whether the increased p75NTR expression in AD is due to the accumulation of proNGF and Rho kinase activation. PC12 cells were stimulated with either proNGF or NGF. Pull-down assay was carried out to determine the RhoA kinase activity. We found the expression of p75NTR was enhanced by proNGF compared to NGF. The proNGF stimulation also increased the RhoA kinase activity leading to apoptosis. The expression of active RhoA kinase was found to be increased in human AD hippocampus compared to control. The addition of RhoA kinase inhibitor Y27632 not only blocked the RhoA kinase activity but also reduced the expression of p75NTR receptor and inhibited the activation of JNK and MAPK induced by proNGF. This suggests that overexpression of proNGF in AD enhances p75NTR expression and activation of RhoA, leading to neuronal cell death.

Plasminogen gene expression is regulated by nerve growth factor

2007 ◽  
Vol 5 (8) ◽  
pp. 1715-1725 ◽  
Author(s):  
A. GUTIÉRREZ-FERNÁNDEZ ◽  
R. J. PARMER ◽  
L. A. MILES
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Growth

Commercial mouse and human nerve growth factors contain nerve growth factor prohormone isoforms

1997 ◽  
Vol 76 (1) ◽  
pp. 75-81 ◽  
Author(s):  
M. Reinshagen ◽  
I. Geerling ◽  
J. Lakshmanan ◽  
H. Rohm ◽  
M.P. Lutz ◽  
...  
Keyword(s):  
Growth Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Growth ◽  
Nerve Growth Factors ◽  
Human Nerve

scholarly journals Seasonal Expression of NGF and Its Cognate Receptors in the Ovaries of Grey Squirrels (Sciurus carolinensis)

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1558
Author(s):  
Margherita Maranesi ◽  
Francesco Alessandro Palermo ◽  
Antonello Bufalari ◽  
Francesca Mercati ◽  
Daniele Paoloni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Breeding Season ◽  
Granulosa Cells ◽  
Reproductive Physiology ◽  
Tyrosine Kinase Receptor ◽  
Grey Squirrel ◽  
Nerve Growth ◽  
Grey Squirrels

The grey squirrel is an invasive alien species that seriously threatens the conservation of the native red squirrel species. With the aim of characterizing the reproductive physiology of this species due to its great reproductive success, the function of the ovarian nerve growth factor (NGF) system was analyzed in a grey squirrel population living in central Italy. During the breeding and nonbreeding seasons, the ovarian presence, distribution, and gene expression of NGF, neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR), as well as NGF plasma concentrations, were evaluated in female grey squirrels. NGF was found in the luteal cells and in the thecal and granulosa cells of follicles, while NTRK1 and NGFR were only observed in follicular thecal and granulosa cells. NGF and NGFR transcripts were almost two-fold greater during the breeding season, while no seasonal differences were observed in NTRK1 gene expression. During the breeding season, NGFR was more expressed than NTRK1. Moreover, no changes were observed in NGF plasma levels during the reproductive cycle. The NGF system seems to be involved in regulating the ovarian cycle mainly via local modulation of NGF/NGFR, thus playing a role in the reproductive physiology of this grey squirrel population.

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