Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prosaposin was identified as a neurotrophic factor stimulating neurite outgrowth in murine neuroblastoma (NS20Y) cells and choline acetyltransferase (ChAT) activity in human neuroblastoma (SK-N-MC) cells. The four naturally occurring saposins, which are derived by proteolytic processing of prosaposin, were tested for activity. Saposin C was found to be active, whereas saposins A, B, and D were inactive as neurotrophic factors. Dose-response curves demonstrated that nanomolar concentrations of prosaposin and saposin C stimulated neurite outgrowth and increased ChAT activity. Prosaposin and saposin C exerted activity by a mechanism independent of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Binding assays utilizing saposin C as a ligand gave two saturable binding constants, a high-affinity (Kd = 19 pM) and a low-affinity (Kd = 1 nM) constant, with 2000 and 15,000 sites per NS20Y cell, respectively. Phosphorylation stimulation experiments demonstrated that brief treatment with prosaposin or saposin C enhanced phosphorylation of a variety of proteins, some of which contained phosphorylated tyrosine(s). Since both cell lines were also stimulated by ciliary neurotrophic factor (CNTF) as well as prosaposin, inhibition was tested by utilizing an anti-gp130 monoclonal antibody, which specifically inhibited CNTF stimulation; this antibody did not inhibit prosaposin or saposin C stimulation. These results indicate that prosaposin and saposin C are neurotrophic factors which initiate signal transduction by binding to a high-affinity receptor that induces protein phosphorylation.
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PMID:Identification of prosaposin as a neurotrophic factor. 793 12

The effect of ciliary neurotrophic factor (CNTF) on beta-amyloid precursor protein (APP) gene expression was investigated in cultured rat C6 glioma cells and human SH-SY5Y neuroblastoma cells. CNTF increased APP mRNA abundance in C6 glioma cells in a dose-dependent manner, with an approximately 3-fold increase in maximum observed after 24 h with a concentration of 1 ng/ml. However, no significant differences in the splicing pattern of the three major isoforms of APP mRNA were apparent between control and CNTF-treated C6 glioma cells. CNTF had no effect on APP mRNA abundance in SH-SY5Y neuroblastoma cells. These findings suggest that CNTF can modulate APP mRNA expression and might affect amyloidogenesis in Alzheimer's disease.
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PMID:Ciliary neurotrophic factor induced-increase in beta-amyloid precursor protein mRNA in rat C6 glioma cells. 794 86

This study used reporter gene constructs containing regulatory regions of the c-fos, vasoactive intestinal peptide, and choline acetyltransferase genes to determine the role of p21ras and protein kinase C in the action of ciliary neurotrophic factor and leukemia inhibitory factor. Down-regulation of protein kinase C with phorbol ester did not affect the induction of either c-fos-beta-galactosidase or vasoactive intestinal peptide-luciferase by ciliary neurotrophic factor or leukemia inhibitory factor. In contrast, while leukemia inhibitory factor induction of choline acetyltransferase-luciferase expression was protein kinase C-independent, there appears to be both protein kinase C-dependent and -independent pathways for induction of choline acetyltransferase-luciferase by ciliary neurotrophic factor. Cotransfection of a dominant-negative mutant p21rasN17 blocked nerve growth factor-mediated induction of c-fos-beta-galactosidase, but did not affect induction of c-fos-beta-galactosidase, vasoactive intestinal peptide-luciferase, or choline acetyltransferase-luciferase by either ciliary neurotrophic factor or leukemia inhibitory factor. Thus, in contrast to the action of nerve growth factor, gene induction by ciliary neurotrophic factor, and leukemia inhibitory factor is ras-independent in IMR-32 neuroblastoma cells.
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PMID:Differential requirements for p21ras and protein kinase C in the regulation of neuronal gene expression by nerve growth factor and neurokines. 803 40

Information on the transmembrane signaling events and subsequent biochemical processes initiated by ciliary neurotrophic factor (CNTF) receptor activation in neurons is lacking. SH-SY5Y cells, a human neuroblastoma cell line expressing CNTF receptors, were used to study metabolic changes associated with functional ligand-receptor interactions. Real-time measurements quantifying the rate of extracellular acidification by SH-SY5Y cells (a measure of metabolic activity) were made using a silicon-based cytosensor. Application of recombinant human CNTF (rhCNTF) to resting SH-SY5Y cells increased their acidification rate in a concentration and time-dependent manner with an apparent EC50 of 60 ng/ml. Pretreatment of cells with phosphatidylinositol-specific phospholipase C (PI-PLC) prevented the CNTF, but not an NGF-stimulated increase in acidification rate. Collectively, these results demonstrate that: (1) SH-SY5Y cells express functional CNTF receptors; and (2) the initial signal transduction mechanism activated by the CNTF receptor in SH-SY5Y cells is distinct from that activated by the NGF receptor; however, both may ultimately stimulate the same downstream biochemical messengers to increase cellular metabolism.
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PMID:Recombinant human ciliary neurotrophic factor stimulates the metabolic activity of SH-SY5Y cells as measured by a cytosensor microphysiometer. 806 84

Differentiation factors have been identified that influence the phenotype of sympathetic neurons by altering expression of classical neurotransmitters and neuropeptides. Investigation of the molecular mechanisms through which such factors act would be facilitated by the availability of a neuronal cell line that responds to these factors in a fashion similar to sympathetic neurons. We have identified a human neuroblastoma cell line, NBFL, that responds to the differentiation factor ciliary neurotrophic factor (CNTF) by coordinately inducing multiple neuropeptide genes as do sympathetic neurons. Treatment of NBFL cells with CNTF increases vasoactive intestinal polypeptide (VIP), somatostatin, and calcitonin gene-related peptide (CGRP) mRNAs but does not change other neurotransmitter properties. The induction of VIP mRNA by CNTF in NBFL cells is dose dependent, rapid, sustained, and independent of new protein synthesis. Genomic 5' flanking sequences located within a 1.59-kilobase region of the human VIP gene and distinct from the previously defined cAMP-responsive element subserve transcriptional activation by CNTF. Further examination of NBFL cells should permit the elucidation of the molecular mechanisms by which CNTF and other differentiation factors coordinately activate neuropeptide gene transcription to influence neuronal differentiation. Similar mechanisms may mediate the effect of CNTF on neuronal survival.
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PMID:Ciliary neurotrophic factor coordinately activates transcription of neuropeptide genes in a neuroblastoma cell line. 809 44

LA-N-2, a cell line derived from a human peripheral neuroblastoma, has a partially cholinergic phenotype and is a potential in vitro model of cholinergic neurons. The object of this study was to enhance the cholinergic phenotype of these cells with differentiation agents to improve the cell line's usefulness as a convenient model of cholinergic function. I treated cells in the presence of serum with 10 microM 5-azacytidine, 2.5 microM bromodeoxyuridine, 2 nM ciliary neurotrophic factor, 1 mM dibutyryl cAMP, 0.25 nM leukemia inhibitory factor and/or 3.8 nM nerve growth factor, N-2 supplement (without serum), or 10 microM retinoic acid for 9-14 days. Treated cells were loaded with [3H]choline for 30 min at 37 degrees and washed. The amounts of cellular and released (5 min, room temperature), labeled and unlabeled acetylcholine and choline were determined by HPLC. None of the differentiation agents induced Ca(2+)-dependent release of [3H]acetylcholine, but 5-azacytidine, dibutyryl cAMP, N-2, and retinoic acid increased Ca(2+)-independent release that was specific for acetylcholine. In addition, 5-azacytidine, bromodeoxyuridine, leukemia inhibitory factor, and N-2 substantially increased [3H]acetylcholine levels, and these increases correlated highly with increases in total acetylcholine levels. Overall, LA-N-2 cells should prove to be a good model for studying cholinergic function.
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PMID:Differentiation agents enhance cholinergic characteristics of LA-N-2 human neuroblastoma cells. 863 28

We have previously reported that ciliary neurotrophic factor (CNTF) mRNA is upregulated in the rat striatum following trauma and that its peak is coincident with a peak in the number of GFAP-positive astrocytes. CNTF, or other neurotrophic factors present in the traumatized striatum, may be involved in the dopaminergic fiber sprouting seen following cavitation or graft implantation in animal models of Parkinson's disease. This study was undertaken in order to further characterize the neurotrophic activity present following trauma through the use of bioassays. Adult rats underwent stereotaxic biopsy of the right striatum, and gelatin sponge [gelfoam (GF)] was placed in the resultant cavity. GF was collected from 1 to 30 days following trauma and homogenized. GF extracts (with equal protein concentrations) were assayed using dorsal root ganglion (DRG) explants, dissociated ciliary ganglia (CG), and human dopaminergic neuroblastoma cell (SH-SY5Y) cultures. The GF extracts had significant neurite-promoting activity (NPA) for DRG, CG, and SH-SY5Y cells, with the maximum effect seen 7 days after trauma. NPA was not blocked by anti-nerve growth factor (NGF) Ab, but anti-brain-derived neurotrophic factor (BDNF) Ab significantly blocked the activity for DRG. The GF extracts protected the SH-SY5Y cells from the neurotoxins 6-OHDA and MPP+, as did NGF and BDNF. This neuroprotective effect of GF was not blocked by anti-NGF Ab. This study suggests that the neurotrophic activity in GF extracts has CNTF-like and BDNF-like components as well as another, undefined component.
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PMID:Traumatized rat striatum produces neurite-promoting and neurotrophic activities in vitro. 865 21

In a cultured hybrid neuronal cell line (BIM) which was produced between human neuroblastoma cells (IMR32) and thymidine auxotrophs (B3T) of rat nerve-like cells (B103), the mRNAs encoding ciliary neurotrophic factor (CNTF) and neurotrophins were detected by the polymerase chain reaction method. The conditioned medium of BIM cells enhanced choline acetyltransferase (ChAT) activity in septal neurons and survival of ciliary ganglion neurons. The mRNA expression of CNTF and neurotrophins in BIM cells was differently regulated by the stimulation with cAMP, FGF and retinoic acid. These data suggest multiple regulation and collaboration of neurotrophic factors.
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PMID:Expression of mRNA encoding neurotrophic factors and its regulation in a hybrid neuronal cell line. 872 6

We have investigated the effects of several neurokine/cytokine family members on the level of alpha-bungarotoxin-binding to neuronal nicotinic acetylcholine receptors. Exposure of human neuroblastoma cells (SH-SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or oncostatin-M resulted in a 30-40% decline in alpha-bungarotoxin receptors on the cells with no decrease seen in either muscarinic acetylcholine receptors or in L-type Ca2+ channels. The level of nicotinic receptor was not affected by the related cytokine, interleukin-6. Treatment of IMR-32 cells with 40 pM CNTF produced a half-maximal decrease of alpha-bungarotoxin binding which compared well with the affinity estimated from binding of 125I-CNTF (Ki approximately 40 pM) and the concentration causing c-fos activation in SH-SY5Y cells, as detected by nuclear run-on assays (60-120 pM). Previous results have indicated that the differentiating agents, phorbol esters and retinoic acid, also decrease nicotinic receptor numbers. Here the effects of CNTF, which did not induce neural differentiation, were enhanced by differentiation with 12-O-tetradecanoylphorbol 13-acetate (10 nM) and prevented by retinoic acid (10 microM). Therefore, the response of neuroblastoma cells to cytokines may be under developmental control. These cells offer a system to examine cytokine responses and signal transduction mechanisms during neural development.
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PMID:Ciliary neurotrophic factor regulates nicotinic acetylcholine receptors on human neuroblastoma cells. 878 99

We have isolated the promoter region and determined the start sites of transcription for the gene encoding the chicken m2 (cm2) muscarinic acetylcholine receptor. Transfection experiments, using cm2-luciferase reporter gene constructs, demonstrated that a 789-bp genomic fragment was sufficient to drive high level expression in chicken heart primary cultures, while an additional 1.2-kb region was required for maximal expression in mouse septal/ neuroblastoma (SN56) cells. Treatment of SN56 cells with the cytokines ciliary neurotrophic factor and leukemia inhibitory factor increases expression of endogenous muscarinic acetylcholine receptors and results in a 4- to 6-fold induction of cm2 promoter driven luciferase expression. We have mapped a region of the cm2 promoter that is necessary for induction by cytokines.
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PMID:Isolation and characterization of the chicken m2 acetylcholine receptor promoter region: induction of gene transcription by leukemia inhibitory factor and ciliary neurotrophic factor. 896 51


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