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)

L-Asparagine is necessary and sufficient for the maximal induction of ornithine decarboxylase (ODC) (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in confluent N18 mouse neuroblastoma cells in a salts/glucose medium; L-asparagine also induces maximal ODC activity when added to a tissue culture medium. L-Glutamine is about one-half as effective as asparagine. Cholera toxin and agents that are known to raise intracellular cyclic AMP concentrations have no effect on the induction of ODC activity unless suboptimal concentrations of asparagine are present in the salts/glucose medium. Whereas actinomycin D does not inhibit induction of ODC activity by asparagine, it inhibits the induction of ODC activity in association with cyclic AMP. In the salts/glucose medium, the rate of loss of ODC activity following the inhibition of protein synthesis by cycloheximide or puromycin depends upon the presence or absence of asparagine; loss is rapid only in the absence of asparagine and does not appear to be related to the inhibition of protein synthesis. These results are discussed in the context that the overlay of the growth medium tends to mask the minimal requirements for enzyme induction, because the composition of the medium defines: (a) the requirements for the induction of ODC activity; (b) the effect, or lack of effect, of cyclic AMP (and of inducers of intracellular cyclic AMP) on the induction of ODC activity; (c) the effect, or lack of effect, of actinomycin D on the induction of ODC activity; and (d) the action of puromycin and of cycloheximide on the rate of loss of ODC activity. It will be interesting to determine whether these results are uniquely applicable to ODC, whether many of the reactions attributed to cyclic AMP in the literature may be mediated by asparagine and glutamine, and whether actinomycin D, cycloheximide, and puromycin can be relied upon to differentiate between transcriptional and post-transcriptional control.
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PMID:Enzyme regulation in neuroblastoma cells in a salts/glucose medium: induction of ornithine decarboxylase by asparagine and glutamine. 19 3

We have developed a clonal variant, named DF-40, from the N2a mouse neuroblastoma cell line, which has the ornithine decarboxylase (L-ornithine carboxylase, EC 4.1.1.17, ODC) gene amplified. When DF-40 cells were maintained in a simple salt glucose medium (e.g. Earle's blanced salt solution), L-asparagine alone was sufficient to induce a maximal increase in ODC activity. The increase in ODC activity correlated well with an increase in the amount of ODC protein. Northern blot analysis indicated that asparagine caused a 12-15-fold increase in ODC mRNA. The half-life of ODC mRNA induced by asparagine in DF-40 cells changed from more than 8 h to about 25 min upon removal of asparagine from the culture in the presence of actinomycin D. In contrast, asparagine had little or no effect on the rate of transcription of the ODC gene. Pulse labeling of cells for 15 min with [35S]methionine showed a 90-140-fold increase in the synthesis of ODC protein after 4-8 h of incubation with asparagine. The removal of asparagine from the medium resulted in a rapid loss of ODC protein with a half-life as short as 12 min. The presence of asparagine increased the half-life of ODC protein by 3-5-fold when measured in the presence of cycloheximide. Taken together, our data show that asparagine induced ODC gene expression in DF-40 cells, primarily by post-transcriptional stabilization of ODC mRNA. In addition, asparagine specifically stimulated the synthesis and suppressed the degradation of ODC protein.
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PMID:Mechanism of regulation of ornithine decarboxylase gene expression by asparagine in a variant mouse neuroblastoma cell line. 155 4

In order to develop a molecular probe to delineate chemical and biological characteristics of human neuroblastoma cells, a murine monoclonal antibody (Mab 5G3) was produced that is directed to a glycoprotein, preferentially expressed on the surface of such cells. This antibody is of IgG2a isotype, has an association constant of 8 X 10(9) M-1, and reacts preferentially with human neuroblastoma cell lines and fresh frozen tissue sections in enzyme-linked immunosorbent assay and immunoperoxidase assays, respectively. Minimal reactivity is observed with a variety of lymphoblastoid cell lines and normal fetal and adult tissues. Mab 5G3 specifically recognizes a neuroblastoma target glycoprotein antigen of 215 kDa that is derived from a 200-kDa precursor, as evident from pulse-chase biosynthetic studies. Treatment with tunicamycin revealed that both molecules contain N-asparagine-linked oligosaccharides; however, only the 215-kDa species is resistant to treatment with endo-beta-N-acetylglucosaminidase H and sensitive to neuraminidase, indicating that it contains trimmed and terminally sialylated oligosaccharides of the "complex" type. In contrast, the 200-kDa precursor is sensitive to endo-beta-N-acetylglucosaminidase H and resistant to neuraminidase treatment indicating that it contains high-mannose non-processed oligosaccharides. The 215-kDa molecule is sulfated, phosphorylated at serine residues, and expressed on the cell surface. A molecule of 200 kDa is detected by Mab 5G3 in spent culture medium of human neuroblastoma cells which is neither sulfated nor phosphorylated.
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PMID:Characterization of a unique glycoprotein antigen expressed on the surface of human neuroblastoma cells. 352 41

The minimum requirements for eliciting or enhancing ornithine decarboxylase activity (EC. 4.1.1.17); L-ornithine carboxylase) in neuroblastoma cells incubated in salts-glucose solutions have been investigated. These incubation conditions permit the study of changes in ornithine decarboxylase activity independently of the growth-associated reactions that occur in cell culture media (Chen, K.Y. and Canellakis, E.S. (1977) Proc. Natl, Acad. Sci. U.S.A. 74, 3791-3795). Ornithine decarboxylase activity can be elicited by a variety of asparagine and other amino acid analogs, including alpha-aminoisobutyric acid, that cannot participate in protein synthesis. Of the eleven asparagine analogs tested, alpha-N-CH3-DL-asparagine is the most potent in eliciting ornithine decarboxylase activity and is equivalent to asparagine in this regard. Inclusion of polar groups into the asparagine molecule results in the loss of its ability to elicit ornithine decarboxylase activity. With the use of these analogs and of analogs of other amino acids it is shown that the rapid fall in ornithine decarboxylase activity that is noted following cycloheximide treatment may not be a consequence of the inhibition of protein synthesis. The rapid fall in ornithine decarboxylase activity is primarily due to the removal of the agent that elicits and stabilizes its activity. These results, the finding that alpha-aminoisobutyric acid stimulates ornithine decarboxylase activity and that sodium is required for the stimulation of ornithine decarboxylase activity are discussed in relation to the "A" amino acid transport system.
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PMID:Studies on the role of protein synthesis and of sodium on the regulation of ornithine decarboxylase activity. 711 71

We have previously shown that asparagine alone induces a 10-15-fold increase in ornithine decarboxylase (ODC) mRNA level in DF-40 mouse neuroblastoma cells. The induction is due to an accumulation of ODC mRNA through a post-transcriptional stabilization mechanism (Chen, Z.P. and Chen, K.Y. (1992) J. Biol. Chem., 267, 6946-6951). In the present study we showed that asparagine induced ODC gene expression in v-Ha-ras-transformed 3T3 (ras-3T3) cells but not in 3T3 cells. Other growth related genes including c-src, c-ras, and c-fos were not affected by asparagine in ras-3T3 cells. Southern blot analysis indicated that the pronounced asparagine effect was not due to ODC gene amplification in ras-3T3 cells. The effect of asparagine on the induction of ODC mRNA could account for the significant increases in the ODC activity in ras-3T3 cells. We also examined the effect of asparagine on ODC gene expression in human KD cells and their transformed counterparts. Our findings strongly suggest that the induction of ODC mRNA by asparagine may represent a component of an altered growth regulatory program associated most prominently with cell transformation.
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PMID:Asparagine markedly induces the expression of ornithine decarboxylase gene in transformed mammalian cells but not in their untransformed counterparts. 795 61

The carbohydrate moieties of glycoproteins in plasma membrane are known to correlate with the induction of cell differentiation in some kinds of cells. We investigated the asparagine-linked sugar chains of neuroblastoma and ganglioneuroma cell membranes. The acidic oligosaccharides were bi-, tri-, and tetraantennary complex-type sugar chains with Man alpha-->(Man alpha)Man beta-->GlcNAc beta-->(+/- Fuc alpha-->)GlcNAc as their cores. A comparative study of the oligosaccharides of these cells showed that the biantennary complex-type sugar chain with bisecting N-acetylglucosamine residues increased and high-molecular-weight oligosaccharides decreased in ganglioneuroma cells. It is suspected that asparagine-linked sugar chains correlate with the differentiation stage of neuroblastoma.
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PMID:Bisected N-acetylglucosamine residue of biantennary sugar chains and high-molecular-weight oligosaccharides of neuroblastoma cell membranes. 826 79

An antigenic double mutant of rabies virus (challenge virus standard [CVS] strain) was selected by successive use of two neutralizing antiglycoprotein monoclonal antibodies, both specific for antigenic site III. This mutant differed from the original virus strain by two amino acid substitutions in the ectodomain of the glycoprotein. The lysine in position 330 and the arginine in position 333 were replaced by asparagine and methionine, respectively. This double mutant was not pathogenic for adult mice. When injected intramuscularly into the forelimbs of adult mice, this virus could not penetrate the nervous system, either by the motor or by the sensory route, while respective single mutants infected motoneurons in the spinal cord and sensory neurons in the dorsal root ganglia. In vitro experiments showed that the double mutant was able to infect BHK cells, neuroblastoma cells, and freshly prepared embryonic motoneurons, albeit with a lower efficiency than the CVS strain. Upon further incubation at 37 degrees C, the motoneurons became resistant to infection by the mutant while remaining permissive to CVS infection. These results suggest that rabies virus uses different types of receptors: a molecule which is ubiquitously expressed at the surface of continuous cell lines and which is recognized by both CVS and the double mutant and a neuron-specific molecule which is not recognized by the double mutant.
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PMID:An avirulent mutant of rabies virus is unable to infect motoneurons in vivo and in vitro. 942 Feb 24

The steroid SC17599 (17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxypregna -3, 5-dien-20-one) has mu-opioid actions in vivo. The ability of SC17599 to interact with opioid receptors has been studied using radioligand and [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) binding assays. SC17599 bound to mu-opioid receptors in SH-SY5Y neuroblastoma cells and to recombinant receptors expressed in rat C6 glioma cells and Chinese hamster ovary cells with good affinity and with greater than 100-fold selectivity for mu- over both delta- and kappa-opioid receptors. Binding was much reduced when aspartate 147 in the wild-type mu-opioid receptor was replaced with asparagine. The affinity of SC17599 for the mu-opioid receptor was decreased in the presence of sodium ions, indicating agonist activity. SC17599 stimulated the binding of [(35)S]GTPgammaS in a naloxone-reversible manner with good potency and maximal effect equivalent to that of the mu-opioid agonists fentanyl and [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. In rat brain membranes, SC17599-mediated stimulation of [(35)S]GTPgammaS binding was reversed by the antagonist naltrexone. SC17599 lacks an aromatic ring and para-hydroxyl substituent considered critical in the pharmacophore for mu-opioids. The structural relationship between SC17599 and more traditional opioid ligands was investigated through genetic algorithm-based modeling techniques for pharmacophore generation (GASP) and ligand-receptor docking (GOLD). The relatively planar and electron-rich A ring of the steroid compensated for the lack of aromaticity. Modeling of ligand-receptor docking showed that both morphine and SC17599 occupy the same binding pocket within the transmembrane helix bundle of the mu-opioid receptor and that the relationship between their binding modes largely mimicked the pharmacophore alignment.
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PMID:The steroid 17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxy-pregna-3, 5-dien-20-one (SC17599) is a selective mu-opioid agonist: implications for the mu-opioid pharmacophore. 1099 35

This study characterized the Na+-dependent transport of L-glutamine by a human neuroblastoma cell line, SK-N-SH. The Na+-dependent component represented >95% of the total glutamine uptake. Kinetic studies showed a single saturable high-affinity carrier with a Michaelis constant (K(m)) of 163 +/- 23 microM and a maximum transport velocity (Vmax) of 13,713 +/- 803 pmol x mg protein(-1) x min(-1). Glutamine uptake was markedly inhibited in the presence of L-alanine, L-asparagine, and L-serine. Li+ did not substitute for Na+. These data show that L-glutamine is predominantly taken up through system ASC. Glutamine deprivation resulted in the decrease of glutamine transport by a mechanism that decreased Vmax without affecting K(m). The expression of the system ASC subtype ASCT2 decreased in the glutamine-deprived group, whereas glutamine deprivation did not induce changes in system ASC subtype ASCT1 mRNA expression. Adaptive increases in Na+-dependent glutamate, Na+-dependent 2-(methylamino)isobutyric acid, and Na+-independent leucine transport were observed under glutamine-deprived conditions, which were completely blocked by actinomycin D and cycloheximide. These mechanisms may allow cells to survive and even grow under nutrient-deprived conditions.
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PMID:Characterization of L-glutamine transport by a human neuroblastoma cell line. 1199 38

Persistent infection of mouse neuroblastoma NB41A3 cells with yellow fever 17D virus generates viral variants which exhibit defective cell penetration, poor cell-to-cell spread, small plaque size and reduced growth efficiency, caused by substitution of glycine for aspartic acid or glutamic acid at positions 360 and 362 in the envelope protein. These positions occur within a charge cluster, Asp360-Asp361-Glu362, located in domain III, near its interface with domain I. To characterize further the molecular basis for the variant phenotype, a series of mutant viruses containing substitutions at position 360, 361 and 362, were studied for effects on the cell culture properties typical of the neuroblastoma-adapted variant. Most substitutions at position 360 gave rise to viruses that were very defective in cell penetration, growth efficiency and cell-to-cell spread, whereas substitution with glutamic acid yielded a virus indistinguishable from parental yellow fever 17D. Substitution with lysine was not tolerated and substitution with asparagine resulted in frequent wild-type revertants. A glycine residue was not tolerated at position 361, but substitution at 362 yielded a small plaque virus, similar to the effect of substitution at position 360. These data indicate that the yellow fever virus E protein contains a locus within domain III where a negative-charge cluster is important for optimal function of this domain in virus-cell interactions beyond the stage of virus attachment. Modelling predictions suggest that the mutations alter the local properties of the loop within domain III, and may compromise interactions of this domain with an adjacent region of domain I during conformational changes that occur in the E protein in association with virus entry.
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PMID:Neuroblastoma cell-adapted yellow fever virus: mutagenesis of the E protein locus involved in persistent infection and its effects on virus penetration and spread. 1565 61


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