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NGF activates cell differentiation. 1000 / 1669
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"Consequently, the aim of this study was to determine whether the rat pheochromocytoma derived PC12 cell line expresses the prodynorphin gene, if it secretes dynorphins, and if the NGF induced differentiation of PC12 cells toward sympathetic neurons affects the secretion of the latter."
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"A well documented example for signal specificity determination is found in rat phaeochromocytoma PC12 cells where epidermal growth factor (EGF) stimulation produces a transient mitogen activated protein kinase (MAPK) activation and leads to cell proliferation while nerve growth factor (NGF) initiates a sustained MAPK activation and induces cell differentiation."
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"We found that the number of neurite bearing cells in wild type and IP 3 3-KA expressing cell types equalised as C5 dose increased, reflecting a dose dependent affinity of C5 for IP 3 3-kinase, and further indicating that the catalytic activity of IP 3 3-kinase opposes NGF driven PC12 cell differentiation."
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"This hypothesis is consistent with a number of previous and recent studies showing that NGF promote differentiation of cultured tumor cells and that single and repeated in vivo subcutaneously [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR], intracerebrally [XREF_BIBR, XREF_BIBR], intranasally [XREF_BIBR], topically [XREF_BIBR - XREF_BIBR, XREF_BIBR - XREF_BIBR] and orally [XREF_BIBR] NGF administered or even endogenously-induced and released NGF [XREF_BIBR] do not cause uncontrolled cell proliferation nor lead to cancer cell generation."
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"Here, we confirm that NGF stimulates SOD2 expression XREF_BIBR, XREF_BIBR, XREF_BIBR in TrkA SH-SY5Y cells (this study), adding to observations that NGF induces Ras and MAPK signalling and neuronal differentiation in TrkA SH-SY5Y cells XREF_BIBR, and suggesting that SOD2 expression in SH-SY5Y cells could be regulated differently by spontaneously active intracellular TrkAIII and NGF activated cell surface TrkA receptors."
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"As neurotrophic factors that are retrogradely transported, NGF and BDNF promoted neuronal growth, differentiation, and survival [XREF_BIBR - XREF_BIBR]; they also acted as factors controlling cholinergically mediated plasticity in the hippocampus through turnover of neurotransmitters such as acetylcholine and dopamine [XREF_BIBR]."
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"For example, different ligands trigger different dynamics of ERK activation epidermal growth factor (EGF) drives transient ERK activation, whereas nerve growth factor (NGF) drives sustained ERK activation), and these different dynamics correlate with different downstream responses (EGF drives the proliferation of PC12 cells, whereas NGF drives the differentiation of PC12 cells)."
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"GP-17 exerted protective effect against Aβ -induced neurotoxicity in nerve growth factor-induced differentiation of PC12 cells, including oxidative stress, apoptosis, and autophagic cell death, which might be related to estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β, and activation of nuclear factor-erythroid 2-related factor 2/antioxidant responsive element/heme oxygenase 1 (Nrf2/ARE/HO-1) pathways [83]."
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"Exposure of PC12 cells to NGF triggers differentiation into sympathetic like neuronal cells, characterized by long-term and stable neurite outgrowth and exhibiting many properties of adrenal medullary chromaffin cells, including catecholamine synthesis, storage, and secretion XREF_BIBR."
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"To assess the role of PLC-gamma1 in mediating the neuronal differentiation induced by NGF treatment, we established PC12 cells that overexpress whole PLC-gamma (PLC-gamma1PC12), the SH2-SH2-SH3 domain (PLC-gamma1SH223PC12), SH2-SH2-deleted mutants (PLC-gamma1deltaSH22PC12), and SH3 deleted mutants (PLC-gamma1deltaSH3PC12)."
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"Some studies showed that, as a potent promoter of mineralization during dentin formation, NGF significantly stimulates DNA synthesis and mineral deposition in cultures of human pulp cells, and induces differentiation of odontoblast-lineage cells with subsequent biomineralization in vitro[24], [25], [26]."
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"This was not accompanied by any changes in the expression of Apaf-1, suggesting that inhibition of caspase-9 activation was not due to down-regulation of Apaf-1 which has been reported to occur during NGF mediated differentiation of sympathetic neurons over 7 days [XREF_BIBR], but instead upstream of apoptosome formation."
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"Inorganic mercury has been shown to change the fate of murine central nervous system stem cells, alter neuronal differentiation, affect neurotransmitter production, alter the conductance of L-type calcium channels, potentiate calcium signals elicited by depolarization or agonist stimulation, enhance NGF induced differentiation in PC-12 cells, and modify calcium signals, thereby activating apoptosis in cell lines [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"The precise mechanism through which NAB2 overexpression leads to lowered levels of p21 WAF1 remains to be elucidated; however, this downregulation is likely to result directly in an inability of these cells to differentiate, as induction of p21 WAF1 has been shown to play an important role in NGF mediated differentiation of PC12 cells."
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"To study whether RICH proteins participate in the extension of neurites or the formation of new branches in neurons, stable transfectants of the pro neuronal PC12 cell line were generated to express high levels of zRICH during the differentiation triggered by NGF treatment (XREF_FIG)."
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"App dephosphorylation during neuronal differentiation seems to be a general characteristic because we observed this phenomenon also in other systems, such as Ngf mediated differentiation of PC12 cells (XREF_FIG) and retinoic-acid-mediated differentiation of neuroblastoma cells (data not shown)."
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"Besides, CBCT examination revealed a better amount of callus formation and reconstruction, and a more uniform distribution of collagen in the bone matrix depending on the effect of exogenous NGF, implying that NGF could promote the proliferation and differentiation of bone cells to reconstruct the mandible (Figs."
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"Consistent with their potency in inducing neurite outgrowth when stimulated with EGF, BPGAP1-BCH, BPGAP1, and BPGAP1-R232A also potentiated a similarly potent neurite outgrowth upon stimulation with a suboptimal level of NGF (10 ng/ml), which by itself did not induce PC12 differentiation (XREF_FIG and XREF_FIG)."
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"For instance, although EGF and NGF trigger similar sets of signaling pathways in PC12 cells including Raf/MEK/ERK XREF_BIBR, XREF_BIBR, PI3K and AKT XREF_BIBR, and PLCgamma pathways XREF_BIBR, XREF_BIBR, EGF induces cell proliferation while NGF induces cell differentiation accompanied by cell cycle arrest XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"For instance, NGF and TrkA induces differentiation, apoptosis, and growth inhibition in neuroblastoma and medulloblastoma (Chou etal., 2000; Lavenius etal., 1995; Matsushima and Bogenmann, 1993), and high expression of TrkA is considered a favorable prognostic indicator in neuroblastoma (Nakagawara etal., 1993)."
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"Subsequent studies revealed that the purified murine NGF (adult submaxillary gland) stimulates morphological differentiation, regulates neuronal gene expression (through interaction with specific cellular receptors) and plays a critical role in mature neurons for acting directly on peripheral sensory and sympathetic neurons and for maintaining their function and phenotype [XREF_BIBR, XREF_BIBR]."
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"Preliminary studies in the nervous system indicate that SH2B3, expressed in cortical neurons from embryonic stages, competes with the other family members (SH2B1 and SH2B2) and inhibits the NGF induced differentiation of PC12 cells reducing the neurite outgrowth of cortical neurons, through binding of its SH2 domain to the NGF receptor and repressing the PI3K pathway XREF_BIBR."
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"Previous studies have suggested that the ERK and MAPK pathway is crucial for NGF induced neuronal differentiation of cells because blocking ERK and MAPK activation inhibits neurite induction, and constitutive activation of the ERK and MAPK pathway results in neurite outgrowth XREF_BIBR."
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"Silencing of FEZ1 by RNA interference (RNAi) strongly inhibited the NGF induced differentiation and efficiently reduced the anterograde transport of mitochondria in PC12 cells, suggesting that FEZ1 is essential for NGF induced neuronal differentiation of PC12 cells XREF_BIBR, XREF_BIBR."
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"From the in vitro culture of muscle derived stem cells, it was observed that the NGF immobilized microspheres induced more neurogenic differentiation than the bFGF immobilized microspheres, as evidenced by a quantitative real-time polymerase chain reaction using specific neurogenic markers (Nestin, GFAP, beta-tubulin, and MAP2) and Western blot (Nestin and beta-tubulin) analyses."
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"Finally, a neurotrophin unbalance has been proposed as an AAS neurotoxic mechanism involving the nerve growth factor (NGF), a member of the neurotrophin family that promotes the differentiation, growth, and survival of specific neuronal populations during development and in the adulthood [XREF_BIBR, XREF_BIBR]."
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"Nerve growth factor (NGF) and dexamethasone, commonly used inducers of differentiation in PC12 cells, produced differentiation without measurable changes in N8-acetylspermidine levels, suggesting that different (or multiple) mechanisms may be involved in these differentiation processes."
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"NGF caused a significant stimulation of granulocyte differentiation from human peripheral blood and murine bone marrow cells, suppressed apoptosis of rodent neutrophils and peritoneal mast cells, enhanced functional properties of murine neutrophils and human eosinophils, and not only promoted colony formation of murine IL-3-dependent bone marrow derived cultured mast cells, but also induced the phenotypic change to connective tissue-type mast cells."
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"We previously elucidated the detailed molecular mechanisms of the nerve growth factor (NGF)-mediated delta opioid receptor (OPRD1 or DOR) gene expression during NGF induced differentiation [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR], showing that sustained activation of phosphoinositol-3-kinase (PI3K)/Akt/nuclear factor kappaB (NF-kappaB) signaling is required for NGF modulated OPRD1 gene expression [XREF_BIBR]."
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"Some of these efforts have involved the use of defined growth factors and growth media supplements, including the use of transforming growth factor (TGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and nerve growth factor (NGF) to induce DPSC differentiation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Interestingly, decreased expression of NF-kappabeta pathway genes has been detected in differentiating hESCs, while IL-2 and NGF have been used to induce differentiation of hESCs to natural killer cells and neurons, respectively, lineages that are distinctly different from the trophectoderm."
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"Also, in PC12 cells, differentiation is triggered by the addition of NGF to the culture media, allowing examination of effects at specific stages of neurodevelopment, beginning at cell replication and extending though differentiation; these types of determinations require coordinated and uniform differentiation of the cell population, a situation that can not be modeled in vivo."
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"Here we provide evidence that MKK7gamma1 blocks NGF mediated differentiation and sustains proliferation by interfering with the NGF triggered differentiation programme at several levels : (i) down-regulation of the NGF receptors TrkA and p75; (ii) attenuation of the differentiation promoting pathways ERK1/2 and AKT; (iii) increase of JNK1 and JNK2, especially the JNK2 54kDa splice variants; (iv) repression of the cyclin dependent kinase inhibitor p21 (WAF1 and CIP1), which normally supports NGF mediated cell cycle arrest; (v) strong induction of the cell cycle promoter CyclinD1, and (vi) profound changes of p53 functions."
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"Similar to inactivation of
VHL, inactivation of TFAM upon
transduction with an effective shRNA, PC12 cell showed no characteristics of
phenotypical changes associated to NGF induced differentiation (Fig. 7d, e), indicating that low
mitochondrial content prevents neural differentiation induced by NGF."
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"During the process of NGF induced differentiation of the cell line, 4 days of MEHP exposure (2.5-250 muM) increased membrane and cytoskeletal protein contents, enhanced NGF induced neurite outgrowth, up-regulated the choline acetyl transferase (ChAT) mRNA and down-regulated tyrosine hydroxylase (TH) mRNA levels, which suggested the promoted differentiation towards the acetylcholine (ACh) phenotype at the expense of the dopamine (DA) phenotype."
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"Three important conclusions emerge from this study : (i) internalization of NGFRs is not necessary for some early rapid transcriptional effects of NGF; (ii) an unknown factor (s) that cooperates with the cloned NGFR in allowing high-affinity NGF binding is found in a primitive central nervous system cell line; and (iii) NGFRs introduced into and expressed by D283 MED (i.e., MED-NGFR) cells are partially functional but are unable to induce differentiation in these primitive neuron like tumor cells, implying that high-efficiency receptor mediated endocytosis of NGF and its receptor may be a necessary step in the cascade of events leading to NGF mediated differentiation."
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"While in the present study, we demonstrate that endogenous Spry4 is a physiological negative feedback regulator of NGF induced neuronal differentiation, previous studies proposed Spry2 and Spry4 as the critical regulators of Erk and MAPK activation related to neuronal cell differentiation in the context of FGF XREF_BIBR, XREF_BIBR."
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"In contrast, the v-erbA oncogene, a mutated, oncogenic version of TR alpha-1, partially but constitutively inhibited NGF- induced neuronal differentiation of PC12 cells and potentiated dexamethasone induced chromaffin differentiation, giving rise to an aberrant " interlineage " cell phenotype."
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"It is possible that the dramatic morphologic changes observed during NGF induced differentiation of PC12 cells are associated not only with increased synthesis in the Golgi apparatus of plasma membrane components such as gangliosides, but also with increased degradation in lysosomes of other plasma membrane components such as sulfatide."
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"These results (1) indicate that the diversity of Ca2+ currents in PC12 cells arise from the expression of three distinct alpha1 and three different beta subunit genes; (2) support a model for heterogenous beta subunit association of the N-type Ca2+ channel in a single cell type; and (3) suggest that the regulation of the N-type Ca2+ channel during NGF mediated differentiation involves an increase in the number of functional channels with no apparent changes in subunit composition."
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"The discovery of the ability of positive allosteric modulators of the AMPA receptor to induce the expression of neurotrophic factors BDNF and NGF, triggering the mechanisms responsible for the survival of existing functioning neurons, as well as growth and differentiation, the formation of new synapses makes the development of new drugs based on tricyclic derivatives of 3,7-diazabicyclo [3.3.1] nonane is especially promising for use in the later stages of post-stroke rehabilitation."
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"In vitro cell culture experiments on mouse neuroblastoma cells showed that ethanol extracts of MAK-5 produced morphological and biochemical differentiation of 75% of the cells [XREF_BIBR], while, in a further recent study, MAK-5 potentiate NGF inducing neuronal differentiation in PC12 cells [XREF_BIBR]."
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"After NGF induced differentiation for 3 days, PC12 cells overexpressing the GFP-Tmod1 and Tmod2 chimera had significantly fewer (1.57 +/- 0.51 neurites and cell) and shorter (29.2 +/- 14.7 mum) neurites than cells overexpressing the mChFP-Tmod2 and Tmod1 chimera, 3.17 +/- 0.63 neurites and cell and 57.5 +/- 16.8 mum, respectively."
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"In the current study, we firstly investigated whether BM-MSCs from NOD mice could effectively differentiate into retinal cells by using a cocktail of brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF), which could induce MSCs differentiation into retinal neuron like cells."
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"Neurotrophic factors (NTs) are family of structurally and functionally related growth factors that include NGF, BDNF, NT-3 and NT-4/5 that stimulate the survival, differentiation and function of neural cells via selective activation of tyrosine kinase receptors (TrkA, TrkB, and TrkC) in the absence or presence of p75NTR."
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"Nerve growth factor (NGF) induced differentiation of PC12 cells, and after 12 days of NGF treatment there were large increases in the levels of the heterotrimeric G protein subunits alpha o1, alpha i1, beta, and alpha s, small increases in those of alpha i2 and alpha q, and a slight decrease in that of alpha o2."
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"The results indicate that coexpression of both low- and high-affinity NGF receptors are not only more efficient in restoration of NGF induced differentiation pathway, but also be able to activate the pro apoptotic activity of low-affinity NGF receptor and make the tumor cells become NGF dependent and irreversibly differentiated."
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"NGF can activate the cell metabolism by binding to specific TrkA receptor, promoting the proliferation and differentiation of nerve cells, and regulating the survival of central and peripheral nerve cells and the growth of axons, thus playing an important role in the repair of nerve cell injury ."
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"Additionally, our data provide the first information on the molecular mechanisms regulating the expression of shootin1 gene : NGF activates the TrkA receptor tyrosine kinase, which results in the activation of a number of intracellular signalling pathways, including PI3K that induces protein expression of isoform-2 of shootin1 only during NGF mediated differentiation of PC12 cells."
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"Our results suggest that (1) different receptor tyrosine kinases use similar patterns of activation of signaling pathways to mediate distinct biological outcomes of cell migration and proliferation, (2) NGF activates signaling proteins in smooth muscle cells similar to those activated during NGF induced neuronal differentiation, and (3) the combinatorial effects of different signaling pathways are important for the regulation of smooth muscle cell migration and proliferation."
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"More experimental data are required to exactly enlighten the mechanism underlying the differentiation induced either by NGF or by nano-roughness, including investigations concerning the possibility that cytoskeletal changes may increase eNOS activity and NO production which can then be involved in ERK phosphorylation together with induction of one or more NOS isoforms."
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"We demonstrate that L5 concentration- and time-dependently reduces cell viability by inducing ATM and H2AX associated DNA damage and LOX-1/p53/caspase-3-dependent apoptosis; moreover, sublytic concentration of L5 inhibits NGF induced neuronal differentiation by LOX-1-mediated suppression of the PI3K and Akt cascade (XREF_FIG)."
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"Among the many downstream signaling pathways that are initiated by the NGF and TrkA signaling pathways, a sustained activation of the Erk1/2 mitogen activated protein kinase signaling pathway is believed to play a necessary role for NGF induced differentiation of PC12 cells i.e. neurite outgrowth."
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"In this study, we established an NGF induced PC12 differentiation model to screen novel compounds that have the potential to induce neuronal differentiation, and further characterized 4,10-Aromadendranediol (ARDD) isolated from the dried twigs of the Baccharis gaudichaudiana plant, which exhibited the capability of promoting neurite outgrowth in neuronal cells in vitro."
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"To test the hypothesis that dual and sustained delivery of GDNF and NGF with different release kinetics can modulate neural differentiation, the morphology of PC12 cells cultured on different scaffolds was investigated and neurite length was measured for determining neural differentiation percentages."
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"The different fates of PC12 pheocromocytoma cells in response to epidermal growth factor (EGF) and nerve growth factor (NGF) are classical examples of temporal control in ERK1/2 signaling, as EGF induced transient activation of ERK stimulates PC12 cell proliferation, whereas NGF sustained stimulus leads to cell differentiation [XREF_BIBR]."
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"In our text mining study, Hia has been linked to nerve growth factor (NGF), a homodimeric protein that acts as a mediator of inflammation in injured tissues, induces neuronal differentiation, promotes neuronal survival and prevents apoptosis in neurons of both central and peripheral nervous systems."
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"In PC12 cells, robust MAP kinase activation induced by EGF and FGF2, respectively, contributes to cellular proliferation, whereas nerve growth factor (NGF) stimulation leads to prolonged activation of MAP kinase through the FRS2alpha-Shp2-Rap1 pathway and to neuronal differentiation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"The neurotrophin nerve growth factor ( NGF ) modulates the growth of human gliomas and is able to induce cell differentiation through the engagement of tropomyosin receptor kinase A ( TrkA ) receptor , although the role played in controlling glioma survival has proved controversial ."
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"For instance, in rat adrenal pheochromocytoma PC12 cells, nerve growth factor (NGF) induces cell differentiation mainly through sustained phosphorylation of ERK [XREF_BIBR - XREF_BIBR], whereas pituitary adenylate cyclase activating polypeptide (PACAP) induces cell differentiation mainly through cAMP dependent CREB phosphorylation [XREF_BIBR - XREF_BIBR]."
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"Previous studies revealed that liganded ERalpha enhanced NGF induced differentiation in PC-12 cells while in the absence of 17beta-estradiol (17betaE2), the expression of ERalpha actually partly suppressed NGF induced neurite outgrowth or expression of neuronal markers [XREF_BIBR]."
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"SuperFect (TM) was originally designed as a DNA transfectant, however Superfect and siRNA dendriplexes have previously been described to successfully knock down the expression of Erbin in rat cheochromocytoma cells (PC12), resulting in a 52% enhancement of NGF mediated differentiation."
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"The time- and dose dependent differentiation triggered by NGF was (1) markedly increased by basic fibroblast growth factor, interleukin-6 or dibutyryl cyclic AMP; (2) diminished by leukemia inhibitory factor or ciliary neurotrophic factor; (3) not potentiated by insulin like growth factor I or progesterone."
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"Early insights into ERK signal specificity came from studies of the PC12 rat pheochromocytoma cell line in which it was shown that sustained ERK activation induced by nerve growth factor (NGF) led to neuronal differentiation while transient ERK activation following EGF treatment elicited a non differentiating proliferative response [XREF_BIBR]."
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"The illumination of NGF’s critical role in neuronal development eventually led to the creation of the “neurotrophic factor hypothesis” and the classical neurotrophic model in which NGF is synthesized and released by target tissues during embryonic development, promoting the growth, differentiation, and survival of neurons in a dose-dependent manner."
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"In rat pheochromocytoma (PC-12) cells, which have been used as an in vitro model system to study the mechanisms of neuronal differentiation, NGF induces their differentiation, leading to the extension of neurites and the development of the characteristics of sympathetic neurons [XREF_BIBR]."
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"This suggests that partial NGF activity is inadequate to drive neuronal differentiation, providing further evidence that there is an optimal level of NGF-TRKA signalling required for neuronal development.Despite the general consensus that proNGF is an apoptotic agent, the data presented here do not support an apoptotic role for the intermediate cleavage forms of proNGF, as the mutation p.R121W which prevented cleavage to mature NGF did not induce apoptosis."
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"Figure XREF_FIG (C) shows that, in keeping with the results previously reported, PC12 cells grown on PLL-glass present a basal level of protein nitration which increases upon NGF induced differentiation at a level similar to the one evaluated for PC12 cells grown on ns-TiO 2 independently from the presence of the inducer NGF."
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"Interestingly, PC12 cells express both NOX1 and NOX2, which are differentially regulated during NGF-induced differentiation such that NOX2 promotes neurite extension, and is down-regulated during the process, while NOX1 opposes neurite extension and is upregulated (Ibi et al., 2006), suggesting different signaling roles depending on the specific NOX isoform."
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"For neuronal differentiation, PC12 cells were treated with 50 ng/ml NGF in a low-serum medium (DMEM supplemented with 2% FBS, 1% penicillin and streptomycin, and 1% L-glutamine) every 24 h for 96 h. Every 48 h, culture media was removed and replaced with fresh media and NGF according to Binnington and Kalisch."
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"In agreement with previous results from Jeon et al XREF_BIBR, NGF promoted the differentiation of axonal neurite of PC12 cells as evidenced by the high concentration of Tau-1 expression, a specific axonal marker, at the terminal tips of neurite when compared to MAP-2 dendritic marker which was more concentrated in the cell body and proximal neurites (XREF_FIG, upper panels)."
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"Although the growth factor effects predominated (e.g., EGF induced maintenance of NSCs and NGF induced neural differentiation), the ECM also played a role, as illustrated by much less extensive NT-3-induced neural and CNTF induced astroglial differentiation on laminin vs. fibronectin [XREF_BIBR]."
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"Because signaling cascades activated by TrkA receptor on cell surface are sufficient to mediate NGF induced survival, but NGF induced differentiation requires internalization of the Trk receptor in PC12 cells, Our observation suggests that NTRAP may be involved in the internalization and/or subsequent endocytic sorting of activated Trk receptors."
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"The hypothesis of Mulhall that early penile size reduction is the result of sympathetic hyperinnervation is based on the fact that nerve growth factor (NGF), a neurotrophin which is released after peripheral nerve damage, induces differentiation of sympathetic neurons and enhances target innervation [XREF_BIBR, XREF_BIBR]."