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 presence of glutamate-induced electrophysiological responses was examined in eight clonal neuroblastoma cell lines with the whole-cell voltage clamp technique. Only N2A cells responded to glutamate superfusion with a concentration-dependent, reversible inward current. Superfusion with the analogues kainic acid, quisqualic acid and N-methyl-D-aspartic acid also evoked inward currents but they had a smaller amplitude. The results indicate that N2A neuroblastoma cells could serve as an in vitro model to study the functional properties of glutamate receptors and associated ion channels.
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PMID:Glutamate-induced inward current in a clonal neuroblastoma cell line. 169 69

A 23-kDa (p23k) rat brain protein was stereospecifically eluted from a 14 beta-bromoacetamidomorphine affinity column, purified to apparent homogeneity by reverse phase HPLC, and partially sequenced. Three degenerate oligodeoxynucleotide probes were synthesized based on this partial amino acid sequence. A rat brain cDNA library was screened using these probes, and a full-length cDNA was isolated. The deduced protein, 187 amino acids long, is rich in glutamic and aspartic acid residues, endowing p23k with a net negative charge at neutral pH. The protein lacks a signal sequence as well as any transmembrane domains. Based on predictions of secondary structure, p23k is a globular protein composed of 30% alpha-helices and 18% beta-pleated sheets. Northern blot analysis revealed p23k transcripts in rat brain, liver, and the mouse x rat neuroblastoma-glioma NG108-14 cell line. Although not an opioid receptor itself, this protein may be associated with such a receptor or be related to a protein that has been shown to be cross-linked to the opioid peptide beta-endorphin.
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PMID:Purification, cloning, and tissue distribution of a 23-kDa rat protein isolated by morphine affinity chromatography. 197 48

Membranes from the neuroblastoma x embryonic retina cell hybrid cell line, N18-RE-105, bind L-[3H]glutamate with a pharmacologic profile consistent with a 'quisqualate-type' brain L-glutamate receptor. We describe here the cytotoxic effect of L-glutamate receptor agonists on intact N18-RE-105 cells. Cytotoxicity was quantitated by measurement of the release of the cytosolic enzyme, lactate dehydrogenase, into the culture medium after addition of L-glutamate and its analogs to the cell culture medium. L-Glutamate (10 mM) and its confirmationally restricted analogs, quisqualate (1 mM) and ibotenate (10 mM), caused cell lysis. In contrast, similar analogs which do not bind to N18-RE-105 cell membranes (kainic acid, N-methyl-D,L-aspartic acid and gamma-aminobutyric acid) were not cytotoxic. L-Glutamate-induced cytotoxicity was eliminated when calcium-free medium was used. Addition of inorganic or organic calcium channel antagonists also reduced the cytotoxicity of L-glutamate, even when 1.8 mM calcium was present in the medium. Cadmium chloride (10 microM) completely blocked L-glutamate toxicity, whereas manganese chloride (150 microM) and lanthanum chloride (25 microM) reduced toxicity by greater than 50%. Dihydropyridine voltage-sensitive calcium channel agonists or antagonists, had little or no significant effect on L-glutamate-induced toxicity. In contrast, the verapamil derivatives, D600 and D888, and the diltiazem derivative, MDL 12,330A reduced L-glutamate toxicity by greater than 50%. These results suggest that a subtype of voltage-sensitive calcium channels is involved in the mechanism of L-glutamate receptor mediated cytotoxicity in this cell line.
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PMID:Calcium-dependent glutamate cytotoxicity in a neuronal cell line. 289 63

Rubrophilin, a unique brain specific polypeptide, was purified to apparent homogeneity from microsomal fractions of bovine brains. The peptide stains pink with Coomassie Brilliant Blue R-250 (C.I. No. 42660) under specific conditions, has an apparent Mr of 53,000, and is acidic with an apparent pI of 4.9. The purification involves initial solubilization of delipidated microsomes in sodium dodecyl sulfate, followed by ammonium sulfate fractionation, reversed ammonium sulfate gradient elution from diatomaceous earth, gel filtration on polyacrylamide (Biogel P-200), gradient elution chromatography from hydroxylapatite, and reverse-phase chromatography from phenyl-Sepharose. A yield of about 5 mg of rubrophilin was obtained from 9 g of microsomal proteins. Amino acid analysis shows that rubrophilin contains only nine amino acids with residues/mol as follows: alanine (102), glutamic acid (97), lysine (65), proline (55), aspartic acid (48), glycine (44), serine (37), threonine (35), and valine (10). Cysteine, methionine, tryptophan, tyrosine, isoleucine, phenylalanine, histidine, and arginine could not be detected. Relative rubrophilin content of vertebrate brains was as follows: mammals greater than birds greater than reptiles greater than fishes. It is present in mouse retina and human neuroblastoma cell cultures but could not be detected in octopus optic lobe or in cultured C-6 rat glioma cells.
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PMID:Purification and properties of rubrophilin: a novel brain specific membrane polypeptide. 380 7

The molecular events associated with beta-amyloid-induced neuronal injury remain incompletely characterized. Using a substantia nigra/neuroblastoma hybrid cell line (MES 23.5) synthetic beta-amyloid 1-40 induced a time and dose-dependent apoptotic cell death which was characterized by cell shrinkage and fragmentation of DNA, and was inhibited by aurintricarboxylic acid (ATA), and cycloheximide (CHX). Following beta-amyloid 1-40 treatment, cyclic GMP, an index of NO synthesis, was increased in MES 23.5 cells. The NO scavenger hemoglobin, as well as the NO synthase inhibitors NG-monomethyl-L-arginine acetate (L-NMMA) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NI0) attenuated such increases. These same inhibitors and scavengers also significantly prevented cytotoxicity. beta-Amyloid also induced an early and transient increase in intracellular calcium as monitored with laser scanning confocal microscopy and Fluo-3 imaging. These induced calcium transients could be significantly blocked by the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801. Pretreatment with MK-801 or removal of extracellular Ca2+ also reduced beta-amyloid-induced NO production and neurotoxicity. Furthermore, beta-amyloid neurotoxicity was greatly enhanced in the absence of Mg2+ or in the presence of glutamate or NMDA. These data suggest that beta-amyloid can lead to apoptotic cell death through a NO mediated process possibly triggered by Ca2+ entry through activated NMDA-gated channels.
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PMID:Cell death induced by beta-amyloid 1-40 in MES 23.5 hybrid clone: the role of nitric oxide and NMDA-gated channel activation leading to apoptosis. 758 71

Several neuropathologic findings in infants and children with human immunodeficiency virus type-1 (HIV-1) infection are different from those observed in adults, probably related to the fact that the retroviral infection occurs in the setting of neuro-development. This report describes the interaction and biologic activity of tat, the HIV-1 trans-activating protein on human neuroblasts. Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been studied for their capability to adhere to tat (full recombinant protein) and to two different peptide residues of it. Both cells adhere to tat and tat46-60 basic domain, although not to tat65-80 residue, which contains the RGD (arginine-glycine-aspartic acid) motif. Adhesion to collagen I was inhibited by preincubating GI-CA-N cells with tat,46-60 although not with tat,65-80 indicating the capability of the basic residue to interfere with collagen I-induced cellular adhesion. The expression of 200-kD neurofilaments induced by collagen I was not induced by tat,46-60 indicating that neural differentiation along the same pathway is not mimicked by this peptide. Neuroblast cell proliferation was not affected by adhesion to tat46-60 nor to tat.65-80 GI-CA-N cells are not permissive to HIV-1 infection. However, proviral DNA was documented in the cell lysate for 14 consecutive in vitro passages, whereas HIV-1 transcription was never detectable. This would exclude the possibility that tat would be transduced by these cells. GI-CA-N stained negative for CD4, although positive for Gal-C, which may explain HIV-1 entry. Results show that immature human neural cells interact with tat protein and/or its basic residue in vitro. A mechanism similar to that herein described would possibly be active in vivo, which may help in clarifying the pathogenic mechanisms of neurologic dysfunction and destruction of the CNS observed in infants infected with HIV-1.
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PMID:Adhesion of human neuroblasts to HIV-1 tat. 855 50

We determined the effects of all-trans retinoic acid (RA) on the levels of delta opioid receptor (DOR) mRNA and N-Methyl-D-Aspartate receptor (NMDAR1) mRNA in neuroblastoma x glioma hybrid cells (NG108-15) by use of quantitative solution hybridization assays. The assays utilized riboprobes complementary to major portions of the coding region of the DOR and NMDAR1 cDNAs. At 10 microM RA a 3-fold increase in DOR mRNA at 48 h, and later (144 h) alterations were observed in NMDAR1 mRNA levels. Northern blot analysis revealed six transcripts for DOR mRNA ranging in size from 8.7 to 2.0 Kb, and three transcripts for NMDAR1 mRNA ranging in size from 4.1 to 3.5 Kb. Neither the size nor the fractional band intensity was affected by RA treatment. The delayed induction of DOR mRNA suggests an indirect mechanism by which RA acts on transcription of this gene. A surprising induction of DOR mRNA by the protein synthesis inhibitor cycloheximide (CHX) suggests that either a repressor molecule or degrading enzymes/proteases may regulate basal levels of this mRNA. Treatment with RA resulted in a concentration- and time-dependent morphological differentiation characterized by increased size of the cell body and the appearance of numerous short and long processes.
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PMID:Retinoic acid-induced increase in delta-opioid receptor and N-methyl-D-aspartate receptor mRNA levels in neuroblastoma x glioma (NG108-15) cells. 886 97

NG108-15 neuroblastoma cells differentiated with 0.1 M of all-trans retinoic acid (RA) were processed for immunohistochemical analysis using polyclonal antisera against the delta opioid receptor (DOR) and the N-Methyl-D-Aspartate receptor (NMDAR1) to determine the cellular sites for possible functional associations between DOR and NMDAR1 receptors. In this study, 6 days of RA treatment resulted in prominent morphological differentiation characterized by the appearance of numerous axon- and dendrite-like processes and formation of networks between the cell clusters. An immunocytochemical approach allowed the demonstration of antibody concentration-dependent differences, not evident in ligand binding studies, in the distribution of DOR and NMDA receptor protein between cell soma and processes. RA-differentiated cultures showed positive DOR-like immunostaining (DOR-LI) throughout the cell bodies as well as on the newly acquired processes. In contrast, NMDAR1-like immunoreactivity (NMDAR1-LI) in the RA-treated cells was detected in the cell soma and processes only with the higher concentration of the antiserum. With the lower concentration of the antibody the NMDAR1-LI was not detected in the processes and was limited to a punctuate subcellular distribution in the soma. The DOR-LI pattern of distribution in NG108-15 cells differentiated with RA appeared to be consistent with the DOR-LI detected in the CNS. The NMDAR1-LI distribution in these cells is similar to brain tissue with respect to its presence on the newly acquired processes. However, it differed from brain in that a much higher abundance of NMDAR1 receptors was observed in the cell soma. This differential distribution of DOR and NMDAR1 receptors in the RA-treated NG108-15 cells could provide a basis for future studies of drug-induced changes in these two receptors.
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PMID:Detection of delta opioid receptor and N-methyl-D-aspartate receptor-like immunoreactivity in retinoic acid-differentiated neuroblastoma x glioma (NG108-15) cells. 898 Dec 41

Several attempts to investigate the bioactive conformation of neuropeptide Y have been made so far. As cyclic peptides are much more rigid than linear ones, we decided to synthesise cyclic analogues of the C-terminal dodekapeptide amide neuropeptide Y Ac-25-36. Cyclisation was performed by side chain lactamisation of ornithine or lysine and glutamic or aspartic acid. The affinity of the 19 peptides ranged from Ki 0.6 nM to greater than 10,000 nM. We found that the size, position, orientation, configuration. and the location of the cycle plays an important role for receptor recognition. Circular dichroic studies have been performed to characterise the secondary structure of each peptide. Receptor binding studies were carried out on human neuroblastoma cell lines SK-N-MC (Y1) and SMS-KAN (Y2), and on rabbit kidney membranes (Y2). The pharmacological and spectral data showed that the alpha-helix content was not the predominant factor for high Y2-receptor affinity. Instead, the location and the size of the hydrophobic lactam bridge, and the conserved C-terminal tetrapeptide (Arg-Glu-Arg-Tyr) seemed to be the main parameters. Using molecular dynamics, the structures of four cyclic peptides (i,i+4) have been investigated and compared with the previously published NMR structure of one of the cyclic peptide analogues. Significant differences have been found in the overall three-dimensional fold of the peptides. The distances between the N- and the C-terminus allow discrimination between peptides with high binding affinity and those with low binding affinity, because of the correlation that was found with the measured affinity. Thus, this study suggests that a turn-like structure and the orientation of the C-terminus towards the N-terminus play major roles for high affinity binding of cyclic dodecapeptides to the Y2-receptor. None of the cyclic segments exhibits significant affinity to the Y1-receptor. Thus, these results support the hypothesis of a discontinuous binding site of neuropeptide Y at the Y1-receptor.
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PMID:The bioactive conformation of neuropeptide Y analogues at the human Y2-receptor. 928 27

Na+-K+-2Cl- cotransporters are important in renal salt reabsorption and in salt secretion by epithelia. They are also essential in maintenance and regulation of ion gradients and cell volume in both epithelial and nonepithelial cells. Expression of Na+-K+-2Cl- cotransporters in brain tissues is high; however, little is known about their function and regulation in neurons. In this study, we examined regulation of the Na+-K+-2Cl- cotransporter by the excitatory neurotransmitter glutamate. The cotransporter activity in human neuroblastoma SH-SY5Y cells was assessed by bumetanide-sensitive K+ influx, and protein expression was evaluated by Western blot analysis. Glutamate was found to induce a dose- and time-dependent stimulation of Na+-K+-2Cl- cotransporter activity in SH-SY5Y cells. Moreover, both the glutamate ionotropic receptor agonist N-methyl-D-aspartic acid (NMDA) and the metabotropic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) significantly stimulated the cotransport activity in these cells. NMDA-mediated stimulation of the Na+-K+-2Cl- cotransporter was abolished by the selective NMDA-receptor antagonist (+)-MK-801 hydrogen maleate. trans-ACPD-mediated effect on the cotransporter was blocked by the metabotropic receptor antagonist (+)-alpha-methyl-(4-carboxyphenyl)glycine. The results demonstrate that Na+-K+-2Cl- cotransporters in neurons are regulated by activation of both ionotropic and metabotropic glutamate receptors.
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PMID:Stimulation of Na+-K+-2Cl- cotransporter in neuronal cells by excitatory neurotransmitter glutamate. 973 Sep 61


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