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)

Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels.
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PMID:Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. 0 56

A method for assessing the binding of 3H-labeled prostaglandin E1 ([3H]PGE1) to cell membranes has been developed and used to study the interaction of [3H]PGE1 with membranes from cultured mammalian cells. Receptor sites were identified by correlation of the potency of a series of compounds to compete for [3H]PGE1 binding sites and to stimulate adenylate cyclase activity, by correlation of rates of binding and change in enzyme activity, and by the correspondence of [3H]PGE1-binding activity with the presence or absence of PGE1-sensitive adenylate cyclase in several clones. In clone B82, a murine L-cell, [3H]PGE1 binds with an activation energy of 14 kcal/mol to a class of sites with an affinity of 0.5 X 10(8) M-1 and a capacity of 150 fmol/mg of protein. Concentration dependence of adenylate cyclase activation by PGE1 (KD =30 nM) and kinetic analysis of [3H]PGE1 binding (k1 = 4 X 10(6) liters/mol/min, k-1 0.15/min) verify this affinity. Concentration dependence and specificity of binding and activation of adenylate cyclases in neuroblastoma clone N4TG1 and N18TG2 substantiate the method. In several clones that lack PGE1-responsive adenylate cyclase, no specific [3H]PGE1 binding is detectable.
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PMID:Binding of (3H)prostaglandin E1 to putative receptors linked to adenylate cyclase of cultured cell clones. 0 51

The binding of adenosine cyclic 3':5'-monophosphate (cyclic AMP) with soluble (100,000 X g supernatant), pellet, and total homogenate proteins from cyclic AMP-induced "differentiated" mouse neuroblastoma cells increased by about two-fold. The extent of binding with soluble proteins was higher than that with pellet proteins. The binding of cyclic AMP with soluble proteins from 5'-adenosine monophosphate-treated, serum-free medium-treated, sodium butyrate-treated, 6-thioguanine-treated, or X-irradiated neuroblastoma cells did not significantly change. When the soluble proteins containing bound cyclic [3H]AMP were filtered through a Sephadex G-25 column, the relative amount of protein-bound cyclic [3H]AMP in differentiated cells was greater than that in malignant cells, but the amount of free cyclic [3H]AMP was correspondingly less. The electrophoretic characteristics of cyclic AMP-binding proteins of differentiated and malignant cells were identical. There were two binding peaks, but the extent of binding at each peak was relatively high in differentiated neuroblastoma cells. An increase in cyclic AMP binding occurred 24 hr after treatment of neuroblastoma cells with prostaglandin E1. This increase was completely blocked by cycloheximide but not by actinomycin D. The binding was heat labile and sensitive to protease action. These data indicate that the increase in binding in differentiated cells is due to an elevation in the levels of binding proteins. The binding of cyclic AMP with soluble proteins from rat glial cells and mouse L-cells did not significantly change after treatment with prostaglandin E1 or an inhibitor of cyclic AMP phosphodiesterase. Cyclic AMP and guanosine cyclic 3':5'-monophosphate bind with the same proteins, but cyclic AMP has about 10-fold higher binding affinity than does guanosine cyclic 3':5'-monophosphate.
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PMID:Binding of cyclic nucleotides with proteins in malignant and adenosine cyclic 3':5'-monophosphate-induced "differentiated" neuroblastoma cells in culture. 17 1

Induction of neurite formation in neuroblastoma cells by dibutyryl cyclic 3':5'-AMP (db-cAMP) or prostaglandin EI (PGE1) was enhanced after enucleation. Cells selected for resistance to db-cAMP were induced to form neurites by db-cAMP or PGE1 only after, but not before enucleation. Inhibition of protein synthesis inhibited neurite induction in nucleated, but not in enucleated cells, and enucleated cells were less sensitive to inhibition of neurite formation by concanavalin A (ConA). Colchicine, vinblastine and cytochalasin B (CB), compounds that interfere with the assembly of microtubules and microfilaments, inhibited induction in both types of cells. It is suggested that enucleation removes a nuclear inhibitor of neurite induction by db-cAMP and PGE1, and that neurite induction in nucleated cells requires that cAMP activates the assembly of microtubules and microfilaments and inactivates the nuclear inhibitor.
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PMID:Nuclear control of neurite induction in neuroblastoma cells. 23 69

In these structure activity studies, the 46 analogs of the 27-amino-acid form of the pituitary-adenylate-cyclase-activating peptide, PACAP(1-27), and the 38-amino-acid form, PACAP(1-38), were either monosubstituted or bisubstituted at positions 1-3, 20 and 21 or N-terminally shortened. All analogs were compared on human neuroblastoma NB-OK-1 cell membranes for their ability to occupy 125I-[AcHis1]PACAP(1-27)-labelled receptors (AcHis, N alpha-acetylhistidine) and to activate adenylate cyclase (in terms of potency and intrinsic activity). The monophasic slope of dose/effect curves on both parameters suggested interaction with one class of PACAP receptor. Residues 28-38 in the C-terminally extended peptide, PACAP(1-38), played a favorable role in recognition, in that receptors coupled to adenylate cyclase were, in general, more sensitive to PACAP(1-38) analogs than to the corresponding PACAP(1-27) analogs. At variance with PACAP(6-27), PACAP(6-38) was well recognized and acted as a potent competitive antagonist (Ki 1.5 nM). Residues 1-3 were all important in enzyme activation: modification of the beta-turn potential gave full agonists (the LAla2 and DAla2 derivatives) or partial agonists (LPhe2 and DPhe2; LArg2 and DArg2; Glu3 and Asn3). Finally, a proper alpha-helix was also important: the combined substitution of Lys21/Lys22 by Gly21/Gly22 decreased the binding affinity sharply.
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PMID:Structural requirements for the occupancy of pituitary adenylate-cyclase-activating-peptide (PACAP) receptors and adenylate cyclase activation in human neuroblastoma NB-OK-1 cell membranes. Discovery of PACAP(6-38) as a potent antagonist. 132 Oct 43

N-terminally shortened analogs of the 27-amino-acid and 38-amino-acid forms of the pituitary-adenylate-cyclase-activating neuropeptide, PACAP(1-27) and PACAP(1-38), were synthesized by a solid-phase method. Systematic deletion of the first 13 amino acids of both PACAP was tested by evaluating their ability to occupy the specific and selective PACAP receptor of human neuroblastoma NB-OK-1 cell membranes and to stimulate adenylate cyclase or, when inactive per se, to inhibit PACAP-stimulated adenylate cyclase activity. For each peptide, the Kact (concentration required for half-maximal adenylate cyclase activation) or Ki [concentration required to shift the dose/response curve of PACAP(1-27) twofold to the right] was in good agreement with the corresponding IC50 [concentration inhibiting 50% of 125I-[AcHis1]PACAP(1-27) binding to membranes], suggesting interaction with the same homogeneous class of adenylate cyclase-coupled receptors. The deletion of the two first amino acids (His1 and Ser2) sufficed to decrease the affinity for receptors and to suppress the capacity to activate adenylate cyclase. The shorter fragments 3-27 and 3-38, 4-27 and 4-38, 5-27 and 5-38, 6-27 and 6-38, 7-27 and 7-38, 8-27 and 8-38, and 9-27 and 9-38 were all competitive antagonists of PACAP(1-27)-stimulated activity with the N-terminally shortened PACAP(1-38) derivatives being 4-30-fold more potent than the equivalent PACAP(1-27) derivatives. In this group PACAP(6-38) was the most potent antagonist (Ki 1.5 nM). Surprisingly, the N-terminally shorter fragments 10-27 and 10-38, 11-27 and 11-38, 12-27 and 12-38, 13-27 and 13-38, and 14-27 and 14-38 were again able to stimulate adenylate cyclase, the smallest fragments, PACAP(14-27) and PACAP(14-38), being the most potent and efficient (Kact 2 microM and 0.1 microM, respectively). In this group of agonists, PACAP(1-38) derivatives deleted at the N-terminus were also more potent than the equivalent PACAP(1-27) derivatives.
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PMID:Antagonistic properties are shifted back to agonistic properties by further N-terminal shortening of pituitary adenylate-cyclase-activating peptides in human neuroblastoma NB-OK-1 cell membranes. 132 69

Northern blot, immunoprecipitation, and gel electrophoretic data demonstrate that the mouse neuroblastoma NB2a/d1 cells express ependymin mRNA and synthesize and release into the culture medium a protein with immunoreactivity and electrophoretic mobility properties identical to ependymin. This is a brain extracellular glycoprotein that has been implicated in the consolidation process of memory formation and neuronal regeneration. In labeling experiments with 35S-methionine, dibutyrylcyclic3',5'-adenosine-monophosphate (dbcAMP) was found to stimulate the expression of ependymin mRNA and the enhanced synthesis and release of ependymin into the culture medium at the same time that dbcAMP stimulation of neurite outgrowth takes place. These results are consistent with the proposed role of the protein in the mechanism of neuronal regeneration and synaptogenesis. The data indicate that the NB2a/d1 cell line is a good model system for studies of the functional properties of ependymin.
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PMID:Dibutyryl cyclic AMP stimulates expression of ependymin mRNA and the synthesis and release of the protein into the culture medium by neuroblastoma cells (NB2a/d1). 132 62

In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.
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PMID:Research on the differentiation of human and murine neuroblastoma cells. 167 82

The effects of metoclopramide (MCP) and bromocriptine (BC) on the growth of neuroblastoma (NB) cells and their influence on the plasma membrane binding of several neurotransmitters were studied. In the first part of this study, in vitro experiments were done with three human and two murine NB cell lines. Dibutyryl cyclic 3',5'-adenosine monophosphate is known to differentiate NB cells in vitro and served as a reference substance during the experiments. MCP significantly reduced the replication rate in NB cells and increased cellular differentiation by morphological as well as by functional criteria. BC, in contrast, stimulated cell replication. Similar to dibutyryl cyclic 3',5'-adenosine monophosphate, MCP increased the binding capacity of the plasma membrane for the beta-adrenergic hormones dopamine and noradrenaline. In the second part, the effects of BC and MCP upon NB tumor growth were investigated in vivo in the mouse. Significant changes in tumor growth were induced; BC promoted and MCP inhibited the NB tumor growth in a dose-dependent relationship. The findings are discussed, along with the observed accompanying changes in serum copper and in the peripheral blood count.
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PMID:Influence of metoclopramide and bromocriptine upon the growth of human and murine neuroblastoma cells. 196 34

PACAP (pituitary adenylate-cyclase-activating peptide)-binding receptors were investigated in membranes from the rat pancreatic acinar cell line, AR 4-2J, the rat hippocampus and the human neuroblastoma cell line NB-OK, by 125I-PACAP(1-27) (amino acid residues 1-27 of N-terminal amidated PACAP) binding and adenylate cyclase activation. The relative binding of 125I-PACAP(1-27) to the receptor, and ability to activate adenylate cyclase were PACAP greater than or equal to PACAP(1-27) greater than PACAP(2-38) greater than PACAP(1-9)-VIP(10-28)(PACAP-VIP) greater than PACAP(2-27) greater than [Ser9,Tyr13]VIP greater than [Tyr13]VIP greater than or equal to [Ser9]VIP greater than or equal to VIP(1-23)-PACAP(24-27)(VIP-PACAP) greater than VIP (vasoactive intestinal peptide). The N-terminal moiety of PACAP(1-27) was more important than the three amino acids at the C-terminus for 125I-PACAP(1-27)-binding site recognition. For rat pancreatic 125I-VIP-binding sites tested with 125I-VIP, the order of binding affinity was PACAP = PACAP(1-27) greater than or equal to VIP = [Ser9]VIP = [Tyr13]VIP = [Ser9,Try13]VIP greater than or equal to PACAP-VIP greater than or equal to VIP-PACAP greater than PACAP(2-38) = PACAP(2-27). Pancreatic 125I-VIP-binding sites, when compared to 125I-PACAP(1-27)-binding sites, showed little specificity and only weak coupling, so that PACAP and VIP-PACAP acted only as partial VIP agonists on adenylate cyclase.
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PMID:Structural requirements for the binding of the pituitary adenylate-cyclase-activating peptide to receptors and adenylate-cyclase activation in pancreatic and neuronal membranes. 199 28


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