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)

Earlier studies in our laboratory have shown that C-6 glial cells in culture exhibit astrocytic properties with increasing cell passage. In this study, we tested the responsiveness of early and late passage C-6 glial cells to various cultures conditions: culture substrata (collagen, poly-L-lysine, plastic), or supplements for the culture medium, DMEM, [fetal calf, or heat inactivated (HI) serum, or media conditioned from mouse neuroblastoma cells (NBCM) or primary chick embryo cultured neurons (NCM)]. Glutamine synthetase (GS) and cyclic nucleotide phosphohydrolase (CNP), astrocytic and oligodendrocytic glial markers, were used. Cell number and protein content increased exponentially with days in culture regardless of the type of the substratum or cell passage. Differences in cell morphology among the three types of substratum were also reflected on GS activity, which rose by three-fold on culture day 3 for cells grown on collagen; thereafter, GS profiles were similar for all substrata. This early rise in GS is interpreted to reflect differential cell adhesion processes on the substrata; specifically, cell adhesion on the collagen stimulated differentiation into "astrocytic phenotype". Analogous to immature glia cells in primary cultures, early passage C-6 glial cells responded to neuronal factors supplied either from NCM or NBCM by expressing reduced GS activity, the astrocytic marker and enhanced CNP activity, the oligodendrocytic marker. Thus, early passage cells can be induced to express either astrocytic or oligodendrocytic phenotype. In accordance with our previous reports on primary glial cells, late passage C-6 cells exhibit their usual astrocytic behavior, responding to serum factors with GS activity. Moreover, whereas NCM or NBCM alone markedly lowered GS activity, a combination with serum restored activity. The present findings confirm our previous observations and further establish the C-6 glial cells as a reliable model to study immature glia.
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PMID:Early and late passage C-6 glial cell growth: similarities with primary glial cells in culture. 257 33

The human neuroblastoma cell line SK-N-SH comprises cells that undergo morphological and biochemical interconversion between a primitive sympathoblast and a variant, epithelial-like cell type which does not express the neuronal characteristics of the SK-N-SH cell line. Since neural crest cells, from which neuroblastomas are presumed to arise, can undergo transdifferentiation in culture from a neuronal phenotype into other cellular phenotypes, particularly into neurilemmal cells and melanocytes, the present study was undertaken to determine whether this capacity is preserved in malignant cells of the peripheral nervous system. Activities for tyrosinase, a melanocyte marker enzyme, and 2':3'-cyclic nucleotide phosphohydrolase, a Schwann-cell marker enzyme, were measured in clones of the two cell types. While no significant differences in 2':3'-cyclic nucleotide phosphohydrolase activity were measurable, tyrosinase activity was detectable only in the flattened neuroblastoma variant cell lines and was comparable to that in some human melanoma cell lines. The tyrosinase activity in neuroblastoma cell variants increased with cell density and was significantly elevated by melanocyte-stimulating hormone and 8-bromo-cyclic adenosine monophosphate, similar to that seen in melanoma cells in culture. Thus, our findings show that human neuroblastoma cells can undergo bidirectional transdifferentiation in vitro between a neuronal and a melanocyte phenotype, possibly reflecting a process which occurs in the patient.
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PMID:Presence and regulation of tyrosinase activity in human neuroblastoma cell variants in vitro. 298 84

1. In NG108-15 neuroblastomaxglioma hybrid cells, ATP stimulates intracellular cyclic AMP formation, which is inhibited by both adenosine (P(1)) and P2 receptor antagonists. In the present study, we examined the effects of several AMP derivatives in NG108-15 cells and mouse neuroblastoma N18TG-2 cells. 2. Adenosine 2'-monophosphate (A2P), adenosine 3'-monophosphate (A3P) and adenosine 5'-phosphosulphate (A5PS) increased cyclic AMP levels with similar concentration-dependencies in NG108-15 cells. 3. Increases in cyclic AMP by AMP derivatives were inhibited by the P2 receptor antagonist PPADS, but not by suramin. Effects of AMP derivatives were also inhibited by P(1) receptor antagonists ZM241385, XAC, DPCPX and partially by alloxazine. The ecto-nucleotidase inhibitor alpha, beta-methyleneADP was without effect. 4. In contrast, AMP derivatives did not change cyclic AMP levels in N18TG-2 cells. Accumulation of cyclic AMP in N18TG-2 cells was stimulated by adenosine A(2) receptor agonists CGS21680 and NECA, but not by ATP or beta, gamma-methyleneATP, agonists for cyclic AMP production in NG108-15 cells. 5. Reverse transcription-coupled polymerase chain reaction (RT - PCR) analyses revealed that N18TG-2 cells express both A(2A) and A(2B) receptors, while NG108-15 cells express mainly A(2A) receptors. 6. AMP derivatives did not affect the P2X and P2Y receptors expressed in NG108-15 cells. 7. These results suggest that A2P, A3P and A5PS act as agonists for cyclic AMP production and that these compounds are valuable tools for determinating the mechanism of ATP-stimulated cyclic AMP response in NG108-15 cells.
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PMID:Effects of AMP derivatives on cyclic AMP levels in NG108-15 cells. 1072 74

Adenosine triphosphate (ATP) can be released in large amounts from (damaged) cells, leading to locally high concentrations. In this study, we investigated the effect of such high concentrations of ATP on neuroblastoma cells. ATP (>or=30 microM) induced apoptosis in the mouse neuroblastoma cell line N1E-115. Activation of the ATP receptor P2X(7) is one of the routes via which ATP has been shown to induce apoptosis. Although the P2X(7) receptor was present in N1E-115 cells, both at the protein and mRNA level, studies with the P2X(7) receptor agonist benzoyl-benzoyl ATP showed that this receptor was not involved in ATP-induced apoptosis. It has been shown previously that adenosine induces apoptosis in N1E-115 cells after transport inside the cell. In this study, both dipyridamole, a nucleoside transport protein blocker, and uridine, a substrate for this transporter, were able to block ATP-induced apoptosis. This indicated that ATP had to be broken down to adenosine to induce apoptosis. The ecto-nucleotidase inhibitors 6-N,N-diethyl-beta-dibromomethylene-D-adenosine-5'-triphosphate (ARL67156) and alpha,beta-methylene adenosine 5'-diphosphate (AOPCP) commonly used to slow breakdown of ATP did not inhibit ATP breakdown appreciably, while the ATP antagonist PPADS inhibited the breakdown of AMP to adenosine; PPADS was also the only compound capable of inhibiting ATP-induced apoptosis. We conclude that the main route of ATP-induced apoptosis in N1E-115 cells was via breakdown to adenosine.
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PMID:Apoptosis induced by extracellular ATP in the mouse neuroblastoma cell line N1E-115: studies on involvement of P2 receptors and adenosine. 1193 44

The role of adenosine 5'-triphosphate (ATP) and P2Y(1) nucleotide receptor in potentiating agrin-induced acetylcholine receptor (AChR) aggregation is being demonstrated in a co-culture system of NG108-15 cell, a mouse neuroblastoma X rat glioma hybrid cell line that resembles spinal motor neuron, with C2C12 myotube. In the co-cultures, antagonized P2Y(1) receptors showed a reduction in NG108-15 cell-induced AChR aggregation. Parallel to this observation, cultured NG108-15 cell secreted ATP into the conditioned medium in a time-dependent manner. Enhancement of ATP release from the cultured NG108-15 cells by overexpression of active mutants of small GTPases increased the aggregation of AChRs in co-culturing with C2C12 myotubes. In addition, ecto-nucleotidase was revealed in the co-culture, which rapidly degraded the applied ATP. These results support the notion that ATP has a role in directing the formation of post-synaptic apparatus in vertebrate neuromuscular junctions.
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PMID:ATP potentiates the formation of AChR aggregate in the co-culture of NG108-15 cells with C2C12 myotubes. 1584 90

Defect of hypoxanthine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease (LND), but the link between HPRT deficiency and the self-injurious behavior of LND is unknown. In a previous study (Pinto et al., J. Neurochem. 72 (2005) 1579-1586) we reported on a decrease in nucleotidase activity in membranes of several HPRT(-) cell lines and fibroblasts from LND patients. Since nucleotidases are involved in ATP-induced signal transduction, in the present study, we tested the hypothesis that P2X and P2Y receptor-mediated signal transduction is impaired in HPRT deficiency. As model we studied rat B103 neuroblastoma cells. Compared to control cells, in HPRT(-) cells, NTP and NDP-induced Ca(2+) influx across the membrane and Ca(2+) mobilization from intracellular stores were impaired. Both P2X and P2Y receptors were involved in the responses. Quantitative real-time PCR revealed reduced expression of receptors P2X(3), P2X(5), P2Y(2), P2Y(4), P2Y(12), P2Y(13) and P2Y(14) in HPRT deficiency. Collectively, HPRT deficiency is associated with abnormal purinergic signaling, encompassing P2X and P2Y receptors and nucleotidases.
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PMID:Impaired P2X and P2Y receptor-mediated signaling in HPRT-deficient B103 neuroblastoma cells. 2198 3

DREAM is a Ca(2+)-dependent transcriptional repressor highly expressed in neuronal cells. A number of genes have already been identified as the target of its regulation. Targeted analysis performed on cerebella from transgenic mice expressing a dominant active DREAM mutant (daDREAM) showed a drastic reduction of the amount of transcript of Ca(2+)-activated nucleotidase 1 (CANT1), an endoplasmic reticulum (ER)-Golgi resident Ca(2+)-dependent nucleoside diphosphatase that has been suggested to have a role in glucosylation reactions related to the quality control of proteins in the ER and the Golgi apparatus. CANT1 down-regulation was also found in neuroblastoma SH-SY5Y cells stably overexpressing wild type (wt) DREAM or daDREAM, thus providing a simple cell model to investigate the protein maturation pathway. Pulse-chase experiments demonstrated that the down-regulation of CANT1 is associated with reduced protein secretion and increased degradation rates. Importantly, overexpression of wtDREAM or daDREAM augmented the expression of the EDEM1 gene, which encodes a key component of the ER-associated degradation pathway, suggesting an alternative pathway to enhanced protein degradation. Restoring CANT1 levels in neuroblastoma clones recovered the phenotype, thus confirming a key role of CANT1, and of the regulation of its gene by DREAM, in the control of protein synthesis and degradation.
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PMID:Ca2+-activated nucleotidase 1, a novel target gene for the transcriptional repressor DREAM (downstream regulatory element antagonist modulator), is involved in protein folding and degradation. 2245 50