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 cytotoxic potential of heterologous rabbit antibody directed against mouse serum albumin (MSA) and alpha-fetoprotein (AFP) was investigated in vitro with a cell line (Hepa) derived from the mouse hepatoma BW7756. Anti-AFP in the presence of complement could kill Hepa cells at concentrations of anti-MSA that were virtually nontoxic. The specificity of the anti-AFP was defined by demonstrating that Hepa cell toxicity was dependent upon and paralleled the secretion of AFP in synchronized cultures. Furthermore, neither antiserum could be shown to be significantly toxic to mouse neuroblastoma cells (Neuro-2A). Immunoglobulin purified from pools of antisera was also highly effective in producing cytotoxicity even in a complement-free system. This reaction proceeded more slowly, requiring nearly 48 hr to reach maximum effect in comparison to the 12 hr for complement-mediated toxicity. MSA and AFP are secreted during different phases of the cell cycle. In cultures arrested by isoleucine starvation, labeled AFP appears in the medium 10 hr after release of the blockade in association with S phase. The appearance of labeled MSA is delayed until the first mitosis. Cytotoxic effects of anti-AFP parallel the secretion of AFP in synchronous cultures. Both antisera could be inhibitory to the secretion and synthesis of the proteins of their antigenic specificity. MSA synthesis was more susceptible to this inhibition than was AFP synthesis. The significance of this phenomenon and its association with the differential cytotoxicity of the antiserum are discussed.
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PMID:The influence of antisera specific for alpha-fetoprotein and mouse serum albumin on the viability and protein synthesis of cultured mouse hepatoma cells. 6 16

Neuroblastoma cells were synchronized by a combined isoleucine plus glutamine starvation. Adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] was measured under basal conditions and in the presence of dopamine, adenosine and prostaglandin (PG) E1. A clear dissociation occurred between the respective evolution patterns of basal and agonist-stimulated adenylate cyclase activities. The magnitudes of the enzyme response to PGE1, adenosine, and dopamine also exhibited different evolution patterns during the cell cycle. Evolution of adenylate cyclase responsiveness to PGE1 during the cell cycle exhibited striking similarities with the intracellular 3':5'-cyclic AMP changes observed elsewhere. Use of theophylline and fluphenazine as specific inhibitors of adenosine and dopamine, respectively, made it possible to demonstrate that adenosine, dopamine, and PGE1 stimulated adenylate cyclase through independent receptor sites. Furthermore, whatever the stage of the cell cycle, responses to these three agonists were not additive, indicating that the receptors of adenosine, dopamine, and PGE1 control the same adenylate cyclase moieties. The data suggest that adenylate cyclase cell content and enzyme responsiveness to specific agonists can be independently controlled.
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PMID:Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. 26 97

Mouse neuroblastoma cells derived from cholinergic clone NS 20 were synchronized by isoleucine plus glutamine starvation. Basal adenylate cyclase activity increased linearly during the different phases of the cell cycle. Pharmacological data are presented indicating that adenosine, dopamine and prostaglandin E1 control through distinct receptors the same adenylate cyclase activity. The demonstration that basal enzyme activity and its responsiveness to the three agonists tested followed different evolution patterns during the cell cycle suggests that enzyme activity (or content) and activity (or number) of enzyme coupled receptors can be independently modulated.
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PMID:[Adenylate cyclase in synchronized neuroblastoma cells: enzyme response during the cell cycle]. 82 49

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

Monolayer cultures of neuroblastoma X glioma hybrid (clonal) cell line NG108-15, synchronized by the isoleucine/glutamine deprivation method, showed maximal expression of opiate binding sites at the same point in the cell cycle at which prostaglandin E1 (PGE1) had a maximum stimulatory effect on cyclic AMP synthesis. However, the capacity of enkephalin [D-Ala2D-Leu5] to block the stimulation of cyclic AMP synthesis by PGE1 was not related to the number of opiate receptors expressed. The Ki for the inhibition of cyclic AMP synthesis by opioid peptides increased substantially during the period of the cell cycle at which maximal expression of opiate binding sites occurred, making the effective level of inhibition of adenylate cyclase activity by 0.1 microM enkephalin [D-Ala2D-Leu5] the same through the cell cycle. Data are presented to suggest that enkephalin receptor coupling to adenylate cyclase, via a GTP-binding protein, is maximal during G1 phase (which may approximate the state of the differentiated neuron) and minimal during S + G2 phase, just prior to cell division, when many receptors are uncoupled.
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PMID:Cell cycle-dependent expression of specific opiate binding with variable coupling to adenylate cyclase in a neurotumor hybrid cell line NG108-15. 631 83

Secretin, a gut-brain peptide, elicited cyclic AMP production in a clone of neuroblastoma cells derived from the C1300 mouse tumor. Adenylate cyclase (EC 4.6.1.1) in plasma membranes from these cells was stimulated by secretin greater than vasoactive intestinal peptide greater than peptide histidine isoleucine amide, but not by the related peptides glucagon, gastric inhibitory polypeptide, or human growth hormone releasing factor. Hill coefficients for stimulation approximated one and the response to submaximal peptide concentrations was additive, as expected for hormones competing for a single receptor associated with the enzyme. Binding of 125I-labeled secretin to the neuroblastoma plasma membranes was saturable, time-dependent, and reversible. The KD determined from kinetic and equilibrium binding studies approximated 1 nM. The binding site displayed marked ligand specificity that paralleled that for stimulation of adenylate cyclase. The secretin receptor was regulated by guanine nucleotides, with guanosine 5'-(beta, gamma-imino)-triphosphate being the most potent to accelerate the rate of dissociation of bound secretin. These findings demonstrate the functional association of the secretin receptor with adenylate cyclase in neuronally derived cells.
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PMID:Secretin receptors on neuroblastoma cell membranes: characterization of 125I-labeled secretin binding and association with adenylate cyclase. 632 61

The Km value of R. nodosus acid lipase was found to be 5 X 10(-2) M and 8 X 10(-3) M with olive oil and tricaprylin respectively. The lipase hydrolyzed triglycerides better than synthetic detergents and methyl esters. When synthetic triglycerides varying in fatty acid chain length were used, maximum hydrolysis was observed with tricaprylin as the substrate. Positional specificity studies indicated a preference for primary esters. The lipase was activated by albumin, NaCl and taurocholate whereas heparin had no effect. The lipase contains a single polypeptide chain with 298 amino acid residues. Glutamic acid and isoleucine were found to be the amino and carboxy-terminal residues, respectively. By gel filtration and SDS-PAGE the molecular weight was determined to be 40,000 +/- 500. The lipase was susceptible to photooxidation in the presence of methylene blue and Rose bengal whereas PMSF and thiol-group specific reagents had no appreciable effect on the lipase activity. NBS inactivated the lipase. Tryptophan residues were found to be essential for the lipase activity.
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PMID:Further studies on the physico-chemical properties of Rhizopus nodosus acid lipase. 673 85

Whole-cell Ca2+ channel currents were recorded in human neuroblastoma (SH-SY5Y) cells, using the perforated-patch technique with 10 mM Ba2+ as charge carrier. Neuropeptide Y (NPY; 10 nM to 1 microM) caused concentration-dependent inhibition of Ca2+ channel currents which were associated with a slowing in current activation kinetics. [Ala31]NPY, a residue 31 L-alanine substituted analogue of NPY, also inhibited Ca2+ channel currents and caused slowing of activation kinetics, but with approximately 6-fold lower potency. In the presence of 100 nM [Ala31]NPY (which itself had little or no effect on currents), the actions of NPY were similar in magnitude to its effects in the absence of the analogue. Our results suggest that substitution of isoleucine for alanine at residue 31 results in a NPY analogue which is a full agonist but with lower affinity for Y2 receptors.
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PMID:Low potency inhibition of Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells by [Ala31]NPY, an L-alanine substituted analogue of neuropeptide Y. 763 88

Mouse neuroblastoma cells (NB) selected for 10,000-fold increased resistance to mycophenolic acid (NB-Myco) showed a 200-500-fold increase in IMP dehydrogenase protein, and the enzyme (IMP: NAD+ oxidoreductase, EC 1.1.1.205) also exhibited a 2400-fold increased ki for mycophenolic acid and reduced catalytic efficiency (Hodges, S.D., Fung, E., McKay, D.J., Renaux, B.S., and Snyder, F.F. (1989) J. Biol. Chem. 264, 18137-18141). The molecular basis of these changes is the subject of the present study. The nucleotide sequence of IMP dehydrogenase cDNA from NB-Myco cells revealed four nucleotide changes. One of these changes did not result in a codon change, and a second one corresponding to methionine-483 was present in the parental NB mouse line. The remaining two nucleotide substitutions and deduced residue changes are: the C to T transition at base 998 relative to initiation of translation, altering threonine-333 to isoleucine; and the C to A transversion at base 1052, altering serine-351 to tyrosine. Evidence was also obtained for IMP dehydrogenase having undergone gene amplification. IMP dehydrogenase mRNA levels were 500-fold increased in NB-Myco cells as compared to parental NB cells. DNA dot blot analysis showed a 25-fold increase in IMP dehydrogenase gene copy number and restriction enzyme analysis revealed similar gene structure for NB and NB-myco cells.
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PMID:Gene amplification and dual point mutations of mouse IMP dehydrogenase associated with cellular resistance to mycophenolic acid. 790 45

Cell culture techniques, high-resolution in vitro 1H NMR spectroscopy, and chromatographic analyses were used to compare the properties of three types of human brain and nervous system tumours. Cell lines were immunocytochemically characterized at all stages in culture with specific antibodies. Intracellular metabolites present in cell extracts were analysed by 1H NMR spectroscopy and by high performance liquid chromatography (HPLC). The spectra from meningiomas, neuroblastomas, and glioblastomas displayed, in addition to similarities-including the presence of signals from leucine, isoleucine, valine, threonine, lactate, acetate, glutamate, choline-containing compounds and glycine-certain distinguishing metabolic features. Spectra from meningiomas featured relatively high signals from alanine. Intense signals from creatine were present in neuroblastoma spectra, while in spectra from glioblastoma they were not detectable. We found statistically significant differences by 1H NMR spectroscopy in the amounts of alanine, glutamate, creatine, phosphorylcholine and threonine among the types of tumours examined. HPLC determinations confirmed that there were also other metabolites specific to a type of tumour, such as taurine, gamma-aminobutyric acid, and serine. We suggest that these findings have potential relevance for the development of non-invasive diagnosis of tumour lineage by 1H NMR spectroscopy in vivo.
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PMID:Characteristic metabolic profiles revealed by 1H NMR spectroscopy for three types of human brain and nervous system tumours. 873 81


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