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)

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used as precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here we used a population of purely cholinergic cells (human neuroblastoma, LA-N-2), incubated in the presence of [methyl-3H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. PtdCho, purified by thin-layer chromatography, contained 90% of the label incorporated into lipids, demonstrating that LA-N-2 cells contained phosphatidylethanolamine N-methyltransferase. Three peaks of radioactive material that cochromatographed with authentic Ac-Cho, choline, and phosphocholine were observed when the water-soluble metabolites of the [3H]PtdCho were purified by high-performance liquid chromatography. Their identities were ascertained by subjecting them to enzymatic modifications with acetylcholinesterase, choline oxidase, and alkaline phosphatase, respectively. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.
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PMID:Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. 347 63

Five opioid peptides (immunoreactivity) derived from their respective opioid precursors were measured in neuroblastoma-glioma hybrid cells (NG 108CC15; pmol/g protein): heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe), 13.0 +/- 2.6; alpha-neoendorphin, 6.6 +/- 0.8; dynorphin A, 4.4 +/- 1.5; dynorphin A 1-8, 1.3 +/- 0.29; beta-endorphin, 0.3 +/- 0.13. These peptides originate from preproenkephalin A (heptapeptide), prodynorphin (alpha-neonedorphin, dynorphin A, dynorphin A 1-8) and proopiomelanocortin (beta-endorphin). The data suggest the expression of all three known opioid precursors in a single hybrid cell line, permitting a simultaneous investigation of the processing of different opioid peptides under identical experimental conditions.
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PMID:Evidence for the expression of peptides derived from three opioid precursors in NG 108CC15 hybrid cells. 356 21

The effects of the potent tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on phosphatidylcholine (PtdCho) metabolism were investigated in the neuroblastoma X glioma hybrid cell line NG108-15. TPA (100 nM) stimulated by 150-200% the release into the medium of 3H radioactivity from cells that had been pre-labelled with [3H]choline. H.p.l.c. analysis of the medium revealed that TPA stimulated the release of only free [3H]choline (212 +/- 11% of control), without affecting such other labelled metabolites as [3H]phosphocholine and [3H]glycerophosphocholine. This effect was concentration-dependent, with a half-maximal effect obtained at 27.5 +/- 6.8 nM, and was observable as early as 5-10 min after exposure to TPA. The TPA-induced release of [3H]choline into the medium was accompanied by a small and variable decrease in cellular [3H]PtdCho (to 93 +/- 4% of control). However, the radioactivity associated with water-soluble cellular choline metabolites (mainly [3H]phosphocholine and [3H]glycerophosphocholine) remained unchanged. TPA also stimulated the release of [3H]choline derived from [3H]PtdCho that had been produced via the methylation pathway from [3H]methionine. These data suggest that phosphatidylcholine may serve as the source of free choline released from the cells in response to TPA. The possible enzymic mechanisms underlying this response are discussed.
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PMID:Stimulation of choline release from NG108-15 cells by 12-O-tetradecanoylphorbol 13-acetate. 356 13

To identify the VIP biosynthetic pathways, we have isolated the human VIP gene, using synthetic oligodeoxynucleotides. These specific hybridization probes were constructed according to the neuroblastoma VIP-cDNA sequence and contained up to 39 bases. The gene structure was deduced by direct chemical nucleotide sequencing. Six exons were thus far discovered; among them two short exons, one encoding VIP and the second encoding PHM-27 (a peptide having a N-terminal histidine and C-terminal methionine amide, closely related in sequence and activity to VIP). As a model system for VIP gene expression, we used a human buccal tumor producing elevated amounts of VIP. In these cells, a major transcript of the VIP-gene was identified as a long RNA containing intron sequences. The occurrence of elevated quantities of a high molecular weight, intron containing, gene transcript which is not processed directly into mature RNA suggests that VIP gene expression may be regulated at the RNA processing level.
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PMID:Structure and expression of the vasoactive intestinal peptide (VIP) gene in a human tumor. 374 44

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

Qualitative aspects of protein synthesis in organelles and intact cultured cells of brain origin were compared to clarify the distinction between synaptosomal and mitochondrial protein synthesis. Brain mitochondria and synaptosomes were isolated either on a traditional Ficoll-sucrose gradient or by a new Percoll gradient procedure, and were incubated in an amino acid incorporation system containing [35S]methionine, then electrophoresed on gradient slab gels. Autoradiography of the gels revealed that in the presence of cycloheximide both mitochondria and synaptosomes synthesized at least 17 proteins in the 6,000-50,000 MW range, and that incubation with chloramphenicol reduced or eliminated these bands. With minor variation these patterns in the low-molecular-weight region also resembled patterns obtained from cycloheximide-inhibited rat liver mitochondria and intact brain cells (cultured glia, glioma, and neuroblastoma). In the higher molecular weight region of the gels (greater than 50,000) banding patterns were more complex and tended to differ between organelles and intact cells. These polypeptides probably reflect nonmitochondrial protein synthesis, and their variable response to inhibitors may account for confusion in the literature with regard to the effects of inhibitors of protein synthesis in brain mitochondria and synaptosomes.
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PMID:Comparison of protein synthesis in mitochondria, synaptosomes, and intact brain cells. 396 18

The concentration of intracellular free calcium ions was measured by spectrofluorometry in suspensions of quin2 loaded neural cell lines: neuroblastoma X glioma hybrid cells (clones 108CC15 and 108CC25) and polyploid rat glioma cells (clone C6-4-2). In these cells, bradykinin elicits a transient increase of the cytosolic Ca2+-activity in a dose-dependent manner (half-maximal effect at about 10 nM). The effect requires the presence of extracellular Ca2+. The time to peak is at most 10 s, the decay to the original level lasts 1 min and is followed by a period of 1-4 min during which Ca2+ activity is slightly below control value. Lys-bradykinin and Met-Lys-bradykinin evoke similar effects as bradykinin, but at concentrations 10 times lower. The cells desensitize upon repeated addition of bradykinin. Under the same conditions des-Arg1-bradykinin, des-Arg9-bradykinin, angiotensin II, substance P, apamin and histamine exerted no influence on the concentrations of free Ca2+. Similar to their effect in neural cell lines, bradykinin and Lys-bradykinin induce in primary astroglia-rich cultures from rat brain an increase in the concentration of cytosolic Ca2+ with the peak reached within 30 s and the decay to the original level lasting approximately 4 min. The significance of this effect of bradykinin on the cytosolic Ca2+-activity is discussed in relation to previous findings that bradykinin in the same cell lines induces a hyperpolarization, a rise of the cyclic GMP level and a breakdown of phosphoinositides.
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PMID:Bradykinin causes a transient rise of intracellular Ca2+-activity in cultured neural cells. 406 82

Changes in the synthesis of concanavalin A binding proteins were analyzed at various times during nerve cell differentiation. Both mouse neuroblastoma cells as well as primary cells isolated from chicken dorsal root ganglia were used in these studies. Conditions were optimized for the biochemical differentiation of these cells, which were pulsed with radioactive methionine at several times during differentiation. Soluble extracts were prepared and optimum conditions for the isolation of those proteins which bind the lectin concanavalin A were determined. Incorporation of radioactivity into specific concanavalin A binding proteins was analyzed by two-dimensional gel electrophoresis and by computerized densitometry of the autoradiographs. Our results show that 10 concanavalin binding proteins are made only in differentiating neuroblastoma cells, and that twelve such proteins are made only in differentiating dorsal root ganglia cells. In addition, the synthesis of several other concanavalin A binding proteins increases dramatically during nerve cell differentiation. This class of proteins is now being further characterized by biochemical and immunological techniques.
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PMID:Changes in synthesis of concanavalin A binding proteins during nerve cell differentiation. 408 85

Binding of [3H]methionine-enkephalin to intact N1E-115 neuroblastoma cells (competing ligand: naloxone) revealed a homogenous population of receptors with a density (Bmax) of 79.0 +/- 6.5 fmol/mg protein (mean SEM, N = 3) and an apparent Kd of 5.33 +/- 1.63 mM. The order of displacement of [3H]met-enkephalin was met-/leu-enkephalin greater than naloxone greater than morphine, suggesting that it is of the delta receptor class. Specific binding was heat-labile, stereospecific and sensitive to Na+. Adding met-enkephalin to intact neuroblastoma caused reductions of both basal and prostaglandin E1-stimulated levels of cyclic AMP (41.4 +/- 4.0% (N = 6) and 45.1 +/- 2.4% (N = 3) of control levels, respectively). Maximum inhibition (naloxone-reversible) was observed as low as 10(-7) M met-enkephalin. Preliminary results suggest that cells grown in cholesterol-supplemented medium show reduced binding of [3H]met-enkephalin.
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PMID:Opiate peptide receptors on intact NIE-115 neuroblastoma: radioligand binding properties, intracellular response, and effects of increasing membrane cholesterol. 609 92

Peripherin (Formerly the Y protein) is found in the peripheral nervous system. This Triton-insoluble protein is characterized by its isoelectric point (5.6), its apparent molecular weight (56,000 daltons) and its peptide map. Peripherin was also observed in a mouse neuroblastoma cell line, NIE 115, where its expression appeared regulated by the presence of an inducer of morphological differentiation. In order to analyze more precisely this control, the presence of peripherin was investigated in several neuroblastoma cell lines which exhibit different morphological patterns of differentiation and in the rat pheochromocytoma PC 12 cell line. Differentiation of these cells was induced with 1-methylcyclohexane carboxylic acid (CCA) and nerve growth factor (NGF), respectively. Peripherin was found in these different cell lines. Moreover, the cellular amount of peripherin appraised by [35S]-methionine incorporation was significatively increased in differentiated cells. In contrast, other cytoskeletal components did not undergo a similar raise. The level at which the control of the peripherin content takes place was studied in a cell-free translation system. Poly(A)-rich RNAs extracted from growing or differentiated NIE 115 cells directed the synthesis of similar amounts of peripherin in a reticulocyte lysate. In contrast, polysomes prepared from differentiated cells and the corresponding polysomal RNA programmed in vitro the synthesis of twice more peripherin than polysomes or polysomal RNA from growth-phase cells. Since peripherin synthesis is enhanced 5 times in living cells, it seems probable that the cellular amount of peripherin is controlled partly at the translational level and partly at the turn-over level.
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PMID:Regulation of peripherin in mouse neuroblastoma and rat PC 12 pheochromocytoma cell lines. 615 88


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