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)

The effect of long-term ethanol exposure on muscarinic receptors was investigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM ethanol for 4 days enhanced both peak and steady-state levels of carbachol-stimulated inositol 1,4,5-bisphosphate increase. An ethanol concentration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [3H]inositol-labeled [3H]phosphatidylnositol 4,5-bisphosphate and increase [3H]inositol trisphosphate and [3H]inositol bisphosphate were also potentiated in ethanol-treated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is mediated via M1 receptors both in ethanol-treated and control cells. Ethanol exposure for 2 or 4 days also caused an increase in [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate binding sites and elevation of [3H]pirenzepine binding, which indicated that the number of muscarinic M1 receptors is increased in ethanol-treated SH-SY5Y cells. These results demonstrate that long-term exposure to ethanol potentiates muscarinic M1 receptor-stimulated activation of phospholipase C in SH-SY5Y cells. This is likely to be explained by an increased number of muscarinic M1 receptors.
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PMID:Long-term exposure to ethanol increases the number and function of muscarinic M1 receptors in human neuroblastoma cells. 876 65

We have examined the actions of alkanols, halogenated ethanol derivatives and diethyl ether on ion current mediated by 5-HT3 receptors in NCB-20 neuroblastoma cells. The alcohols and diethyl ether potentiated 5-HT3 receptor-mediated ion current at concentrations that had no effect on membrane current when applied in the absence of agonist. The potency of alcohols increased with increasing hydrophobicity. However, the maximal efficacy of alcohols was unrelated to hydrophobicity. Interactions between different drugs applied simultaneously to cells were examined to determine whether these compounds compete for a distinct modulatory site associated with the 5-HT3 receptor. Analysis of interactions observed at different drug concentrations indicated a variety of interactions between different compounds, ranging from negative to positive allosteric interactions. Interactions between trichloroethanol (TCEt) and isopentanol exhibited characteristics that might indicate competition for a single site of action. However, further examination of interactions between these two drugs indicated that although isopentanol altered the efficacy of co-applied TCEt, TCEt did not have a similar effect with respect to isopentanol. Furthermore, isopentanol did not alter the potency of TCEt for potentiation of receptor function. The absence of competitive interactions among alcohols indicates that a single "alcohol receptor" cannot be defined using established pharmacologic approaches. Our findings are most consistent with the idea that alcohols interact with several hydrophobic sites associated with the 5-HT3 receptor.
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PMID:Pharmacologic characteristics of potentiation of 5-HT3 receptors by alcohols and diethyl ether in NCB-20 neuroblastoma cells. 876 25

In the present study transcriptional activities has been measured with different fragments of the 5'-flanking sequence of the human monoamine oxidase (MAO) genes linked to human growth hormone which was used as a reporter gene. SH-SY5Y neuroblastoma cells and 1242 MG glioma cells were compared under basal conditions as well as after treatments with different drugs. Under basal conditions, the relative reporter activities of the different promoter fragments were similar for both cell lines. No changes in promoter activities, were observed when cells were treated with L-deprenyl, lithium chloride or raclopride. In contrast, increases (2-3-fold) in both reporter gene expression and enzyme activity were observed after ethanol treatment of cells transfected with MAO-B fragments. Gel retardation analysis showed that ethanol caused changes in transcription factor binding to the MAO-B core promoter in both the SH-SY5Y and 1242 MG cell lines in a cell-type specific fashion.
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PMID:Monoamine oxidase gene transcription in human cell lines: treatment with psychoactive drugs and ethanol. 883 30

We have shown that ethanol inhibits uptake of adenosine by a specific nucleoside transporter in NG108-15 neuroblastoma x glioma cells and that cAMP-dependent protein kinase (PKA) activity is required for this inhibition. After chronic exposure to ethanol, adenosine uptake is no longer inhibited on rechallenge with ethanol, i.e. transport has become tolerant to ethanol. Here we show that protein kinase C (PKC) contributes to ethanol-induced tolerance of adenosine transport. Activation of PKC by phorbol esters in control cells results in an ethanol-tolerant phenotype, similar to that produced by chronic ethanol exposure. In addition, chronic exposure to ethanol increases the amounts of alpha, delta, and epsilon PKC. However, reducing PKC activity by inhibition with chelerythrine during chronic exposure to ethanol or down-regulation by phorbol esters prevents the development of ethanol-induced tolerance of adenosine transport. By contrast, the inhibition of PKA activity produces tolerance to ethanol inhibition of adenosine uptake. When protein phosphatase inhibitors are present, inhibiting PKA activity has no effect on ethanol sensitivity of adenosine uptake, suggesting a role for protein phosphatases in the regulation of ethanol sensitivity of uptake. Taken together, our results suggest that PKA and PKC have opposing effects on the ethanol sensitivity of adenosine transport; PKA activity is required for ethanol sensitivity, and PKC activation produces tolerance. Based on these data, we propose that chronic ethanol exposure increases PKC activity, leading to the activation of a protein phosphatase (1 or 2A). This phosphatase then dephosphorylates a PKA-phosphorylated site, which is required for ethanol to inhibit adenosine uptake. Therefore, the sensitivity of adenosine transport to ethanol appears to be maintained by a balance of PKA and protein phosphatase activities, and PKC may regulate phosphatase activity.
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PMID:The role of protein kinase C in cellular tolerance to ethanol. 891 Jun 14

The aim of this study was to investigate the effect of ethanol exposure on the expression of fos and jun genes. Exposure of human neuroblastoma SH-SY5Y cells to ethanol for 2-4 days caused a dose-dependent increase in c-jun and junD mRNA levels, whereas mRNAs for c-fos, fosB and junB were not detectable in control or ethanol-treated cells. Four days of ethanol exposure also enhanced the AP-1 binding activity. Experiments with actinomycin D demonstrated that ethanol did not influence the degradation of c-jun and junD mRNAs. These results demonstrate that long-term exposure to ethanol increases c-jun and junD expression. This effect may be one of the mechanisms through which ethanol influences the gene regulatory system in neuronal cells.
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PMID:Ethanol exposure increases expression of c-jun and junD in human neuroblastoma cells. 893 Sep 87

The intracellular signal cascade transducing muscarinic-receptor-stimulation to gene expression was investigated in human neuroblastoma SH-SY5Y cells. Naive and ethanol-exposed SH-SU5Y cells were stimulated with carbachol (CCh) and inositol 1,4-5-trisphosphate (IP3), 1,2-diacylglycerol (DAG), and c-fos mRNA levels were analyzed using a radioreceptor assay (IP3) thin-layer chromatography (DAG) and Northern blot (c-fos mRNA). Application of the muscarinic agonist CCh induced a rapid increase in (IP3), peaking within seconds after the CCh-addition. There was also an accumulation of DAG reaching maximum after 5 min of receptor-stimulation. Stimulation with CCh also induced expression of the immediate-early gene c-fos in these cells. These events were mediated via muscarinic M1 receptors and the inhibitory effects of H7, staurosporin, and RO31-7549 on the c-fos expression indicated that it was mediated via protein kinase C. Acute exposure to 100 mM ethanol inhibited the formation of IP3 and the expression of c-fos. These effects were due to an increase in the EC50 of CCh for the events. Exposure to 100 mM ethanol for 4 days caused a potentiation of these two events. The EC50 was unaffected but the maximal response was increased. These data indicate that this signal transduction system is inhibited by acute exposure to 100 mM ethanol, an effect that is compensated for after exposure to ethanol for 4 days.
Alcohol Alcohol Suppl 1994
PMID:Muscarinic receptor-stimulated expression of c-fos in neuroblastoma cells. 897 23

Technical limitations are associated with conducting successful in situ hybridization. In this study, three cell types including a tumor neuroblastoma cell line (Neuro-2a), an oligodendrocyte primary culture, and a nonneuronal acute lymphoblastic leukemia cell line (Reh) were used to conduct successful nonradioactive in situ hybridization. Two cDNA probes were used. A 1 kb probe was used to identify the expression of proteolipid protein (PLP) mRNA in a primary culture of oligodendrocytes. A 760 bp cDNA was used to identify the expression of ubiquitin C-terminal hydrolase (UCH-L1) mRNA in Neuro-2a and Reh cells. The probes were labeled with digoxigenin-11-dUTP, denatured, and hybridized with cells fixed on coverslips. The efficiency of the labeling was tested using dot blot analysis by comparing the intensity of our labeled probes with known concentration of the probe labeled by the provider. The nonspecific signals were washed off, followed by detection of a signal specific to the gene. The specificity of the probes was determined by treating the cells with RNase A, hybridizing with bacterial Dig-labeled cDNA (pBR322) and hybridizing the tissues in the absence of labeled probe. During the labeling step, we found that addition of co-precipitants, such as tRNA or glycogen, during precipitation of the labeled probe followed by overnight incubation at -20 C is essential for good recovery of labeled cDNA. Dissolving the labeled probe in a buffer solution containing sodium dodecyl sulfate improves the quantity of the labeling. At the cellular level, prehybridization treatments optimize the permeability of the cell and allow efficient penetration of the labeled probe. Fixing with paraformaldehyde or an ethanol-acetic acid mixture can preserve the structure of cultured cells. To increase the signal to noise ratio, cells were treated with 0.2 N HCl followed by extensive washes using a solution with a high salt concentration and containing dextran sulfate. This treatment significantly improves the signal and reduces the background in cell cultures, but not in tissue sections. The ability to reuse the labeled probe-hybridization mixture is another advantage for using nonradioactive in situ hybridization.
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PMID:Nonradioactive in situ hybridization histochemistry in leukemic and nonleukemic culture. 906 9

Phospholipid base-exchange enzymes catalyze the incorporation of nitrogenous bases into phosphoglycerides by a calcium-dependent mechanism. In this study, we describe the effect of ethanol on the incorporation of radioactive serine, choline and ethanolamine into their respective phospholipids in a neuroblastoma x glioma hybrid cell line (NG 108-15). Long term ethanol exposure induced a potentiation of the incorporation of [14C]serine into phosphatidylserine. Moreover, the phosphorus content of PS was found to be increased after long-term ethanol exposure. No concomitant changes in the phosphorus content of other phospholipids were observed. The results indicate that in NG 108-15 cells, the incorporation of radiolabelled serine into PS is potentiated during chronic ethanol exposure.
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PMID:Ethanol potentiates the uptake of [14C]serine into phosphatidylserine by base-exchange reaction in NG 108-15 cells. 913 35

Long-term regulation of opioid binding was studied in the human neuroblastoma NMB and in the murine lymphoma R1.1 and R1.EGO cell lines. Binding was down-regulated following prolonged exposure to opioid agonists and up-regulated following exposure to antagonist. Down-regulation was inhibited by the metabolic blocker sodium-azide and by the protein kinase H-7. Up-regulation was blocked by the protein and mRNA synthesis blockers cycloheximide, alpha-amanitin and actinomycin D. A significant difference was found between the response of neuronal and immune cells to ethanol exposure: while opioid binding in neuroblastoma culture underwent a pronounced (75%) up-regulation, no effect of ethanol on opioid receptors in lymphoma cultures was detected. The described cell lines present an excellent experimental model to study long-term regulation of opioid receptors in the nervous and immune systems and to elucidate the biological effects of chronic use of opiates and alcohol.
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PMID:Long-term regulation of opioid receptors in neuroblastoma and lymphoma cell lines. 918 44

Iron (Fe) chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class may be useful agents to treat Fe overload disease and also cancer. These ligands possess high activity at mobilizing 59Fe from neoplastic cells, and the present study has been designed to examine whether their marked activity may be related to an energy-dependent transport process across the cell membrane. Initial experiments examined the release of 59Fe from SK-N-MC neuroblastoma (NB) cells prelabelled for 3 h at 37 degrees C with 59Fe-transferrin (1.25 microM) and then reincubated in the presence and absence of the chelators for 3 h at 4 degrees C or 37 degrees C. Prelabelled cells released 4-5% of total cellular 59Fe when reincubated in minimum essential medium at 4 degrees C or 37 degrees C. When the chelators desferrioxamine (DFO; 0.1 mM) or PIH (0.1 mM) were reincubated with labelled cells at 4 degrees C, they mobilized only 4-5% of cellular 59Fe, whereas as 37 degrees C, these ligands mobilized 21% and 48% of cell 59Fe, respectively. The lipophilic PIH analogue, 311 (2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone; 0.1 mM), which exhibits high anti-proliferative activity, released 10% and 53% of cellular 59Fe when reincubated with prelabelled cells at 4 degrees C and 37 degrees C, respectively. Almost identical results were obtained using the SK-Mel-28 melanoma cell line. These data suggest that perhaps temperature-dependent mechanisms are essential for 59Fe mobilization from these cells. Interestingly, the metabolic inhibitors, 2,4-dinitrophenol, oligomycin, rotenone, and sodium azide, markedly decreased 59Fe mobilization mediated by PIH, but had either no effect or much less effect on 59Fe release by 311. Considering that an ATP-dependent process was involved in 59Fe release by PIH, further studies examined 4 widely used inhibitors of the multi-drug efflux pump P-glycoprotein (P-gp). All of these inhibitors, namely, verapamil (Ver), cyclosporin A (CsA), reserpine (Res) and quinine (Qui), decreased 59Fe mobilization by PIH but had little or no effect on 59Fe release mediated by analogue 311. Further, both CsA and Ver increased the proportion of ethanol-soluble 59Fe within cells in the presence of PIH, suggesting inhibited transport of the 59Fe complex from the cell. However, when PIH-mediated 59Fe release was compared between a well characterized Chinese hamster ovary cell line (CHRB30) expressing high levels of P-gp and the relevant control cell line (AuxB1), no appreciable difference in the kinetics of 59Fe release were found. In contrast, it was intriguing that the CHRB30 cells released more 59Fe into control medium (i.e., without PIH) than the AuxB1 control line (16.7% compared to 5.9%, respectively). In summary, the results suggest that a temperature- and energy-dependent process was involved in the efflux of the PIH-59Fe complex from the cells. In contrast, 59Fe release mediated by 311 was temperature-dependent but not energy-dependent, and could occur by simple diffusion or passive transport. Further studies investigating the membrane transport of Fe chelators may be useful in designing regimes that potentiate their anti-neoplastic effects.
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PMID:Mobilization of iron from neoplastic cells by some iron chelators is an energy-dependent process. 918 79


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