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 M current, IM, a voltage-dependent non-inactivating K+ current, was recorded in NG108-15 neuroblastoma x glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25-50 microM) arachidonic acid first increased and later decreased the current, Ih, which holds the membrane potential at -30 mV and mainly flows through open M channels. It shifted the midpoint potential, Vo, of the relation between M conductance, gM, and membrane potential, V, to more negative values and decreased the maximum conductance gM and the time constant tau M. In smaller concentrations (5-10 microM) arachidonic acid merely decreased Ih and gM with little effect on Vo and tau M. Eicosatetraynoic acid and docosahexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i.e. caused a biphasic change in Ih. Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of Ih and gM. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism.
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PMID:The effect of arachidonic acid on the M current of NG108-15 neuroblastoma x glioma hybrid cells. 148 72

Significant differences in the rate of reduction of two spin labels, 5-doxylstearic acid and TEMPOL, in the undifferentiated and differentiated NB-15 mouse neuroblastoma cells were demonstrated by using electron paramagnetic resonance (EPR) spectroscopy. The half-time (T1/2) values for decay of the EPR signal of 5-doxylstearic acid in the undifferentiated and differentiated neuroblastoma cells were 70 min and 290 min, respectively. The T1/2 values of TEMPOL in the undifferentiated and differentiated cells were 18 min and 34 min, respectively. The cellular reductant was characterized as non-protein-bound sulfhydryl groups. A corresponding difference in the cellular non-protein-bound sulfhydryl content, 19.30 nmol/mg protein for the undifferentiated cells and 6.78 nmol/mg protein for the differentiated cells, was observed. Comparison of the reduction rates of TEMPOL, 5-doxylstearic acid and 16-doxylstearic acid in the undifferentiated NB-15 cells suggested that the permeation of non-protein-bound sulfhydryl compounds from the cytosol to membrane may be responsible for the reduction of the lipid-soluble stearic acid spin labels.
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PMID:Differences in the reduction kinetics of incorporated spin labels in undifferentiated and differentiated mouse neuroblastoma cells. 298 18

Inhibitors of arachidonate metabolism and perturbants of the oxidation-reduction state of the cell were employed to develop a pharmacologic profile for muscarinic receptor-mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Several lipoxygenase inhibitors [eicosatetraynoic acid (ETYA), nordihydroguaiaretic acid (NDGA), FPL 57231, FPL 55712, BW755c, propylgallate, and AA861] blocked the elevation of [3H]cyclic GMP induced by muscarinic receptor activation. The cyclooxygenase inhibitors indomethacin and ibuprofen were two orders of magnitude less potent in blocking the muscarinic receptor-mediated [3H]cyclic GMP response than in blocking cyclooxygenase in other systems. ETYA and NDGA did not affect the muscarinic inhibition of the prostaglandin E1-mediated increases in [3H]cyclic AMP levels in N1E-115 cells. ETYA did not have a reproducible effect on the muscarinic receptor-induced release of inositol phosphates. Thus, these lipoxygenase inhibitors appeared to be selective for the effector system coupled to the low-affinity muscarinic agonist-receptor conformation, i.e. that which induces cyclic GMP formation. Other effective inhibitors of the cyclic GMP response were methylene blue, catalase, bromphenacyl bromide, retinal, dithiothreitol, quinacrine, and oxidized glutathione. The antioxidant alpha-tocopherol in the concentration range of 100 microM to 1 mM potentiated the receptor response. Arachidonic acid itself was an inhibitor of the muscarinic receptor-mediated cyclic GMP response (IC50 = 45 microM). Linoleic acid and oleic acid were less potent (IC50 = 130 and 190 microM, respectively), and stearic acid was ineffective. When arachidonic acid was air-oxidized, its inhibitory potency was increased 10-fold. Most but not all of the spontaneously-produced oxidative metabolites, separable by reverse-phase high pressure liquid chromatography, were inhibitory to the receptor response. Enzymatically synthesized 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid inhibited the muscarinic receptor [3H]cyclic GMP response, with IC50 values of 17 and 8 microM respectively. Catalase was effective in blocking the muscarinic cyclic GMP response (IC50 = 5 microM) while having no effect on either the muscarinic receptor-induced inositol phosphate release or the reduction of cyclic AMP levels. Thus, the effector system for increasing cyclic GMP in these cells displays may of the expected characteristics for the involvement of a lipoxygenase or a related enzyme that oxidatively metabolizes arachidonate in order to activate the guanylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Blockade of N1E-115 murine neuroblastoma muscarinic receptor function by agents that affect the metabolism of arachidonic acid. 301 48

The effects of changed ionic environments on the frog taste nerve responses to the bitter substances were examined. The responses to quinine and strychnine carrying a positive charge were suppressed by an increase in ionic strength of stimulating solutions. It was concluded that electrostatic interaction of these positive bitter substances with the receptor membranes greatly contributes to the adsorption of the substances on the membranes and that this interaction was suppressed by an increase in ionic strength. The responses to neutral bitter substances (caffeine and theophylline) were unchanged by an increase in salt concentration. The zeta potential of the mouse neuroblastoma (N-18 clone), which was depolarized by various bitter substances similarly to a taste cell, was measured in the presence of the bitter substances. The zeta potential was a little changed by quinine and practically unchanged by strychnine, caffeine and theophylline. The membrane fluidity of the N-18 cell monitored with 2-(9-anthroyloxy)stearic acid was changed in response to the bitter substances, while the fluidity monitored with 12-(9-anthroyloxy)stearic acid or 1,6-diphenyl-1,3,5-hexatriene was unchanged. This suggested that the bitter substances are adsorbed on the hydrophobic region near the surface and induce a conformational change at the region. The depolarization by the bitter substances seems to stem from changes in the "boundary potential" at the region near the surface within the membrane interior.
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PMID:Contribution of electrostatic and hydrophobic interactions of bitter substances with taste receptor membranes to generation of receptor potentials. 348 63

The mouse neuroblastoma cell (N-18 clone), which is independent of an olfactory cell, was depolarized by 20 odorants examined, suggesting that specific proteins are not required for reception of odorants. The mechanism of non-receptor-mediated odor discrimination was examined using the N-18 cell. Changes in the membrane fluidity of the cell induced by adsorption of odorants were measured with various fluorescence probes, which monitor the fluidity at the different depth and in the different phase of the membrane. The profiles of the membrane fluidity changes monitored with these dyes were different from one species of odorants to another, suggesting that odorants having different odors are adsorbed at different sites in the membranes. The alteration of the lipid composition of the cell membrane brought about by exogenous application of stearic acid and cholesterol led to modification of the responses (magnitude of depolarization) to various odorants. The extent and direction (increase or decrease) of changes in the responses greatly varied among species of odorants. The following mechanism on odor discrimination was proposed. A membrane composition of each olfactory cell is postulated to be different from cell to cell. Different combinations of lipids and proteins in the membranes provide different adsorption sites for odorants. Relative amounts of the membrane potential changes in many olfactory cells in response to an odorant are characteristic of the species of the odorant. The response profiles at the cell level determine the quality of the odor.
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PMID:Evidence for non-receptor odor discrimination using neuroblastoma cells as a model for olfactory cells. 407 64

In this study the effects of experimental modifications of plasma membrane lipid lateral mobility on the electrical membrane properties and cation transport of mouse neuroblastoma cells, clone Neuro-2A, have been studied. Short-term supplementation of a chemically defined growth medium with oleic acid or linoleic acid resulted in an increase in the lateral mobility of lipids as inferred from fluorescence recovery after photobleaching of the lipid probe 3,3'-dioctadecylindocarbocyanide iodide. These changes were accompanied by a marked depolarization of the membrane potential from -51 mV to -36 mV, 1.5 h after addition, followed by a slow repolarization. Tracer flux studies, using 86Rb+ as a radioactive tracer for K+, demonstrated that the depolarization was not caused by changes in (Na+ + K+)-ATPase-mediated K+ influx or in the transmembrane K+ gradient. The permeability ratio (PNa/PK), determined from electrophysiological measurements, however, increased from 0.10 to 0.27 upon supplementation with oleic acid or linoleic acid. This transient rise of PNa/PK was shown by 24Na+ and 86Rb+ flux measurements to be due to both an increase of the Na+ permeability and a decrease of the K+ permeability. None of these effects occurred upon supplementation of the growth medium with stearic acid.
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PMID:Effect of fatty acids on plasma membrane lipid dynamics and cation permeability in neuroblastoma cells. 629 65

The profiling of total long-chain fatty acids and cholesterol in a variety of biological materials, using capillary gas chromatography with flame ionization detection, is described. The within-run precision and day-to-day precision for fifteen fatty acids and cholesterol in erythrocyte samples were investigated. Quantitative data on the analysis of amniotic fluid samples collected from women in the 30th to 38th week are given together with a correlation study on their lecithin/sphingomyelin and their palmitic acid/stearic acid ratios. In addition, the method was applied to lumbar cerebrospinal fluid, plasma, isolated leukemic blood cells and neuroblastoma tissue.
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PMID:Capillary gas chromatographic profiling of total long-chain fatty acids and cholesterol in biological materials. 666 7

The effect of inhibited bioenergetics and ATP depletion on membrane composition and fluidity was examined in cultured neuroblastoma-glioma hybrid NG108-15 cells. Sodium cyanide (CN) and 2-deoxyglucose (2-DG) were used to block, oxidative phosphorylation and anaerobic glycolysis, respectively. Endoplasmic reticulum (ER) Ca(2+)-pump activity measured by 45Ca2+ uptake was > 92% inhibited in intact cells incubated with CN (1 mM) and 2-DG (20 mM) for 30 min. In addition, exposure of cells to CN and 2-DG caused a 134% increased release of isotopically labeled arachidonic acid (3H-AA) or arachidonate-derived metabolites from membranes. Removal of Ca2+ from the incubation medium ablated the CN/2-DG induced release of 3H-AA or its metabolites. Membrane fluidity of intact cells was measured by electron spin resonance spectroscopy using the spin label 12-doxyl stearic acid. The mean rotational correlation time (tau c) of the spin label increased 49% in CN/2-DG exposed cells compared to controls, indicating a decrease in membrane fluidity. These results show that depletion of cellular ATP results in inhibition of the ER Ca(2+)-pump, loss of AA from membranes, and decreased membrane fluidity. We propose that impaired bioenergetics can increase intracellular Ca2+ as a result of Ca(2+)-pump inhibition and thereby activate Ca(2+)-dependent phospholipases causing membrane effects. Since neurons derive energy predominantly from oxidative metabolism, ATP depletion during brain hypoxia may initiate a similar cytotoxic mechanism.
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PMID:Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line. 813 64

In the human neuroblastoma cell line SK-N-BE(2), arachidonic acid (AA), supplied in the medium at micromolar concentrations, markedly enhanced [14C]stearic acid (SA) (but not [14C]palmitic acid or [14C]oleic acid) incorporation into phosphatidylinositol (PtdIns). AA failed to stimulate [14C]SA incorporation into PtdIns precursors, namely phosphatidic acid and cytidinediphosphodiacylglycerol: furthermore, enhanced [14C]SA incorporation, brought about by exogenously administered AA, was not restricted to PtdIns tetraenoic species. When cells were pulsed for 1 h with [14C]SA (either in the presence or absence of AA) and then reincubated in AA- and [14C]SA-free medium, a marked loss of radioactivity from PtdIns was observed, that however was restricted to molecular species other than tetraenoic. These results are discussed in the light of possible mechanisms through which PtdIns achieves the 1-stearoyl-2-arachidonoyl configuration.
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PMID:Arachidonic acid modulates [14C]stearic acid incorporation into phosphatidylinositol, in human neuroblastoma cells. 904 41

We investigated whether zinc deficiency can affect plasma membrane rheology. Three cell lines, human leukaemia T-cells (Jurkat), rat fibroblasts (3T3) and human neuroblastoma cells (IMR-32), were cultured for 48 h in control medium, in zinc-deficient medium (1.5 microM zinc; 1.5 Zn), or in the zinc-deficient medium supplemented with 15 microM zinc (15 Zn). The number of viable cells was lower in the 1.5 Zn group than in the control and 15 Zn groups. The frequency of apoptosis was higher in the 1.5 Zn group than in the control and 15 Zn groups. Membrane fluidity was evaluated using the 6-(9-anthroyloxy)stearic acid and 16-(9-anthroyloxy)palmitic acid probes. Membrane fluidity was higher in 1.5 Zn cells than in the control cells; no differences were observed between control cells and 15 Zn cells. The effect of zinc deficiency on membrane fluidity at the water/lipid interface was associated with a higher phosphatidylserine externalization. The higher membrane fluidity in the hydrophobic region of the bilayer was correlated with a lower content of arachidonic acid. We suggest that the increased fluidity of the membrane secondary to zinc deficiency is in part due to a decrease in arachidonic acid content and the apoptosis-related changes in phosphatidylserine distribution.
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PMID:Influence of zinc deficiency on cell-membrane fluidity in Jurkat, 3T3 and IMR-32 cells. 1462 98


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