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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify the functional significance of type IV phosphodiesterase (PDEIV) in neurons and glia cells [3H]rolipram binding and phosphodiesterase (PDE) activity were examined in cytosol and membrane fractions of neuroblastoma N18TG-2 and glioma C6Bu-1 cells. [3H]Rolipram binding was highly observed in cytosolic fractions of N18TG-2 compared to C6Bu-1. Binding was hardly observed in membrane fractions of both types of cells. Rolipram strongly (70%) inhibited the hydrolytic activity of cAMP in cytosolic fractions of N18TG-2. The activity in cytosol fractions of C6Bu-1 was slightly (20%) inhibited by rolipram. These results suggest that PDEIV plays important roles in neurons.
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PMID:[3H]Rolipram binding and phosphodiesterase activity in neuroblastoma N18TG-2 and glioma C6Bu-1. 752 96

Effects of bradykinin (BK) on the membrane conductance and level of cytoplasmic free Ca2+ in undifferentiated and differentiated neuroblastoma-glioma hybrid (NG108-15) cells were studied using the nystatin-perforated patch-clamp technique and fura-2 fluorometry. Under voltage clamp at -20 mV, undifferentiated cells responded to BK at > 10(-9) M, producing a biphasic current composed of an apamin-sensitive Ca(2+)-activated K+ outward current and non-specific cationic inward current. Both current components corresponding to a biphasic elevation of [Ca2+]i were completely prevented by an intracellular perfusion with EGTA (1 mM) under conventional whole cell recording condition. Undifferentiated cells revealed almost no voltage sensitive Ca2+ current. In NG108-15 cells differentiated with 8-Br-cyclic AMP (1 mM) or rolipram (1 mM), an inhibitor of type IV phosphodiesterase, BK concentration required for the non-specific cationic current with amplitude of > 100 pA was much greater than that of undifferentiated cells. This suggests that the differentiated cells decreased BK-sensitivity in induction of the non-specific cationic current. The non-specific cationic channel is suggested to play roles as a source of Ca2+ entry in undifferentiated NG108-15 cells.
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PMID:Bradykinin-evoked non-specific cationic current in neuroblastoma-glioma hybrid (NG108-15) cells and its down-regulation through differentiation. 752 42

A comparison of the effects of various phosphodiesterase (PDE) inhibitors upon cellular cAMP levels was undertaken in human neuroblastoma SH-SY5Y cells. When inhibitors such as rolipram and Ro 20 1724 (selective for the low Km cAMP-specific PDE) were used, cAMP levels were seen to rise dramatically under basal (< or = 60 fold) or forskolin-stimulated (< or = 200 fold) conditions. However, the non-selective PDE inhibitor isobutylmethylxanthine (IBMX) was 7-18% as effective as these other agents even at 1 mM. The poor efficacy of IBMX was not attributable to concomitant increases in cGMP, to alterations in cAMP egress or to a lack of sensitivity of the cellular PDEs to IBMX inhibition. In additivity experiments, IBMX potently and rapidly reduced cAMP that had accumulated after rolipram treatment. The fact that the agonist 2-chloroadenosine can enhance cAMP accumulation in these cells, and that cAMP elevated by rolipram or forskolin can be reduced by adenosine deaminase and theophylline suggest that cell-derived adenosine enhances cAMP in these cells in an autocrine fashion. Since IBMX is an adenosine receptor antagonist, it is suggested that its blockade of endogenous adenosine effects is at least partly responsible for its poor response when compared to other PDE inhibitors which are weaker adenosine receptor antagonists. These results forewarn against assuming that similar levels of cAMP accumulate after application of PDE inhibitors in these cells.
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PMID:Comparison of the effect of isobutylmethylxanthine and phosphodiesterase-selective inhibitors on cAMP levels in SH-SY5Y neuroblastoma cells. 768 30

2-5A Synthetase and 2-5A phosphodiesterase were determined by analytical capillary isotachophoresis in comparison to radioenzymatic methods. By means of isotachophoretic analysis, a frequently used radioenzymatic 2-5A synthetase assay was optimized and the results of both assays were compared. Using the isotachophoretic assay the influence of interferon-related cytokines (tumor necrosis factor-alpha and interleukin-2) on 2-5A synthetase induction in neuroblastoma cells was estimated. In contrast to mononuclear blood cells, the tumor necrosis factor induced 2-5A synthetase in these cells. 2-5A Phosphodiesterase was determined using an isotachophoretic assay and a radioenzymatic method. Degradation of A2'p5'A2'p5'A (trimeric form of 2-5A core) was measured by isotachophoresis whereas degradation of a mixture of phosphorus-32 labeled 2-5A cores was registered by radioenzymatic assay. Activity of 2-5A phosphodiesterase was only insignificantly enhanced by interferon in mononuclear blood and neuroblastoma cells. In contrast to the radioenzymatic assays, an accurate determination of 2-5A synthetase as well as of 2-5A phosphodiesterase is possible using the isotachophoretic method because the reactions are followed by measuring the substrates ATP and A2'p5'A2'p5'A, respectively.
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PMID:Determination of 2-5A synthetase and 2-5A phosphodiesterase in neuroblastoma cells by analytical capillary isotachophoresis: effects of cytokines and comparison with radioenzymatic methods. 814 79

In neuroblastoma x glioma NG108-15 hybrid cells, opioid agonists inhibited both basal and prostaglandin E1-stimulated adenylate cyclase activities assayed in the presence of the phosphodiesterase (PDE) inhibitors isobutylmethylxanthine and ZK62711 (rolipram). However, when intracellular [3H]cAMP was measured in the absence of the PDE inhibitors the maximal inhibitory level was increased, using the opioid agonist D-Ala2,D-Leu5-enkephalin. This increase in opioid activity was due to agonist stimulation of cAMP degradation, because when the degradation rate of [3H] cAMP was measured in intact hybrid cells it was observed to increase from the control value of 0.495 +/- 0.003 min-1 to 0.760 +/- 0.003 min-1 in the presence of 1 microM D-Ala2,D-Leu5-enkephalin; this was reversed by naloxone. Dose-dependent studies with various opioid agonists, partial agonists, and antagonists revealed that there was a direct correlation between the abilities of these opioid ligands to inhibit adenylate cyclase activity and to stimulate PDE activity, with enkephalin and its analogs being the most potent agonists. Chronic agonist treatment also resulted in a reduction of the opioid agonist stimulation of cAMP degradation, with an apparent decrease in the PDE activity upon addition of naloxone after chronic treatment. However, treatment of the hybrid cells with pertussis toxin, which attenuated the agonist inhibition of adenylate cyclase activity, did not abolish this opioid response. When selective inhibitors for various types of PDE were used, the type I PDE inhibitor W-7 attenuated the opioid effect, whereas the type II PDE inhibitor trequinsin (HL725), the type III PDE inhibitor indolidan, and the type IV PDE inhibitor rolipram had no effect on opioid-stimulated cAMP degradation. The stimulation of type I PDE activity by delta-opioid receptors was independent of extracellular Ca2+ and was not observed with membrane preparations. Therefore, in NG108-15 cells delta-opioid receptors regulate intracellular cAMP levels by coupling to a pertussis toxin-insensitive guanine nucleotide-binding protein, resulting in an increase in intracellular Ca2+ and in Ca2+/calmodulin-dependent PDE activity.
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PMID:delta-Opioid receptor activates cAMP phosphodiesterase activities in neuroblastoma x glioma NG108-15 hybrid cells. 838 86

Characterization of 'low Km' 3':5' cyclic nucleotide phosphodiesterase activities (PDE) expressed in mouse N18TG2 neuroblastoma cells is reported. At least 3 peaks of activity were isolated by DEAE chromatography, none of which was calcium-calmodulin stimulated and cGMP stimulated or inhibited. A first peak elutes at 200 mM sodium acetate; it specifically hydrolyzes cGMP with a Km of 4.7 microM and shows sensitivity to zaprinast [M&B 22948] (1.8 microM). A second peak eluting at 410 mM sodium acetate hydrolyzes both cyclic nucleotides. A third peak, specific for cAMP hydrolysis, elutes at 580 mM sodium acetate, has a Km of 3.2 microM and is sensitive to RO 20 1724 (7.6 microM) and rolipram (2 microM). Hydrodynamic analysis showed for the first peak a Stokes radius of 5.3 nm with a sedimentation coefficient of 8.1 S, a frictional ratio (f/fo) of 1.41 and a native molecular mass of 182 kDa. The same analysis for peak 3 showed a Stokes radius of 4.1 nm with a sedimentation coefficient of 3.2 S, a frictional ratio of 1.63 and a native molecular mass of 56 kDa. The biochemical features reported for the enzyme eluting in the first peak, and its cGMP-binding activity stimulated by inhibitors of phosphodiesterase activity, demonstrate that it belongs to the PDE V subfamily; on the other hand the cAMP specific enzyme eluting in the third peak can be assigned to the 'RO 20 1724 inhibited' form. The significance of these findings is discussed in relation to the functional characteristics of the N18TG2 cell line.
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PMID:Characterization of 3':5' cyclic nucleotide phosphodiesterase activities of mouse neuroblastoma N18TG2 cells. 838 2

Two putative human oligodendroglioma cell lines were examined for the expression of the oligodendrocyte-associated genes, 2',3'-cyclic nucleotide-3'-phosphodiesterase, myelin basic protein, myelin proteolipid proteins, and myelin-associated glycoprotein. The expression of these genes also was examined in control astrocytoma and neuroblastoma cell lines. In addition, the expression of the non-oligodendrocyte-specific genes, glial fibrillary acidic protein (GFAP), neuron-specific enolase and neurofilaments (NF) NF-L and NF-M also were examined. All the cell lines expressed 2',3'-cyclic nucleotide 3'-phosphodiesterase, neuron-specific enolase, and vimentin, and none expressed myelin-associated glycoprotein. The "oligodendrocyte-specific" myelin proteolipid protein mRNAs and the "neuron-specific" NF-L mRNA were expressed in the two astrocytoma cell lines, which also expressed GFAP. Expression of intermediate filament protein genes was more restricted. The astrocytoma, neuroblastoma, and oligodendroglioma cell lines expressed only GFAP, NF-M, and cytokeratin K7, respectively. These results: (a) provide molecular data confirming the classification of the two cell lines as oligodendrogliomal and suggest that their molecular profiles are indicative of immature oligodendrocytes; (b) demonstrate the expression of cytokeratins in oligodendrogliomal cell lines and suggest that apparent GFAP expression in oligodendrogliomas detected by immunocytochemical methods may be due to cross-reactivity with cytokeratins, with which they share common polypeptide sequence; and (c) indicate that astrocytoma cell lines can exhibit a "mixed" phenotype, expressing genes associated with fully differentiated oligodendrocytes and neurons.
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PMID:Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas. 841 42

Cyclic nucleotides levels and cyclic nucleotide phosphodiesterase (PDE) activities were measured in human neuroblastoma NB-OK-1 cells possessing atrial natriuretic peptide (ANP) receptors of the A type and pituitary adenylate cyclase activating polypeptide (PACAP)-preferring receptors. Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) degradation were interrelated since the increase in cGMP, induced by ANP-(99-126), stimulated the hydrolysis of cAMP by PDE isoenzyme II. In intact NB-OK-1 cells, the levels of cAMP and cGMP attained in the presence of, respectively, 1 nM PACAP-(1-27) and 10 nM ANP-(99-126), and in the absence or presence of PDE inhibitors, strongly suggested that cAMP hydrolysis was mainly achieved by isoenzyme IV, and to a lesser extent by isoenzymes I, II, and III, while cGMP was degraded by isoenzymes I, II, III, and V. More than one-half of total cAMP- and cGMP-hydrolyzing activities was present in the membrane-bound fraction. Cyclic nucleotide PDE activities separated by anion-exchange chromatography showed that isoenzymes III and IV were mainly present in the membrane fraction, while isoenzymes I, II, and V were in the cytosolic fraction.
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PMID:Role of phosphodiesterase II in cross talk between cGMP and cAMP in human neuroblastoma NB-OK-1 cells. 877 55

Transcriptional regulation of the rat tyrosine hydroxylase (TH) gene by prostaglandin E2 (PGE2) was investigated in human neuroblastoma SK-N-BE(2)C cells. Prostaglandins increased intracellular cAMP in the presence of 3-isobutyl-1-methylxanthine (IBMX), a cAMP phosphodiesterase inhibitor. Among the prostaglandins tested for their cAMP raising property PGE2 was the most effective. The results suggest that the cells express adenylyl cyclase-linked prostanoid receptors that have a higher affinity for PGE2 than for any other naturally occurring prostaglandin. The treatment of cells with PGE2 increased the TH gene expression approximately 2-fold, even though the cAMP accumulation induced by PGE2 alone was almost negligible. Simultaneous treatment with PGE2 and IBMX enhanced the gene expression concomitantly with a marked accumulation of cAMP. Transient transfection assays with 5' upstream serially deleted constructs of the rat TH gene promoter region fused to the chloramphenicol acetyltransferase (CAT) gene revealed that a cAMP response element (CRE) located at -45 to -38 from the start of the TH gene was essential for the enhancement of TH gene expression by PGE2. Site-directed mutagenesis and specific deletion within the sequence of the CRE motif abolished the transcriptional enhancement by PGE2. In addition, a protein kinase A (PKA) inhibitor, H89, specifically blocked the PGE2 effect on TH gene expression. Northern blot analysis revealed that the increase in TH gene transcription with PGE2 is associated with an elevated TH mRNA level. Gel retardation and competition assays confirmed that the binding of nuclear factors to the CRE site was sequence specific and was augmented by PGE2. Our data indicate that PGE2 enhances transcription of the TH gene mediated by the CRE motif through the activation of PKA. They also suggest that the signal flow from the adenylyl cyclase-linked prostanoid receptor to the nucleus is efficient although cAMP accumulation is not prominent.
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PMID:Transcriptional enhancement of tyrosine hydroxylase by prostaglandin E2 in SK-N-BE(2) C cells. 880 26

Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimulating factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/ nucleotide pyrophosphatase family. PD-Ialpha was found as a brain-type ecto-phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-Ialpha are alternative splicing products from one gene. ATX stimulates motility of A2058 melanoma cells in vitro; however, it has not been known if PD-Ialpha/ATX is expressed in naturally occurred human tumors. In this study, we examined the expression of the human PD-Ialpha/ATX gene in human neuroblastoma tumor tissues and the motility stimulating activity of recombinant ATX on neuroblastoma cells and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell line. The PD-Ialpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma patients to varying degrees. This gene is also expressed in the SMS-KAN neuroblastoma cell line. We identified both isoforms, PD-Ialpha and ATX, in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanomolar concentration. We situated the promoter region, which is essential for its transcription in SMS-KAN cells, at -287 to -254 nucleotides by the promoter activity assay. The gel-shift assay revealed that there exists a nuclear protein in SMS-KAN cells that binds this region. These new insights about autocrine tumor cell motility-stimulating protein will help us to understand the metastatic mechanism of human neuroblastoma.
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PMID:Expression and transcriptional regulation of the PD-Ialpha/autotaxin gene in neuroblastoma. 919 34


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