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)

We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.
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PMID:Manipulation of the fate of long chain polyunsaturated fatty acids in cultured cells. 925 Jun 4

Early ethanol exposure depletes neurons in the developing nervous system, however the effects on neuronal precursors are not homogeneous. Some cells are more susceptible to ethanol toxicity than others. Growth factors are important mitogens for neuronal precursors. We tested the hypothesis that the differential sensitivity of neuronal precursors to ethanol is determined by their responses to growth factors using an in vitro model (SH-SY5Y, SK-N-SH, and IMR32 neuroblastoma cells) of neuronal precursors. The three cell lines were raised in a medium containing 10% or 0% fetal calf serum. Cells were exposed to ethanol and/or a growth factor. These factors included basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor-I, nerve growth factor, and platelet-derived growth factors AA and BB. The numbers of cells per culture were counted both before and after 3 days of ethanol and/or growth factor treatment. In addition, the effect of ethanol exposure on the expression of receptors for these growth factors was examined. Neuroblastoma cells displayed differential sensitivity to ethanol. The growth of SH-SY5Y and SK-N-SH cells was inhibited by ethanol in a concentration-dependent manner. Ethanol did not affect cell viability. Thus, this inhibition resulted from a reduction of cell proliferation. In contrast, IMR32 cells were not affected by ethanol (even at concentrations as high as 800 mg/dl). The response to growth factors was also heterogeneous. In serum-supplemented medium, SH-SY5Y and SK-N-SH cells were stimulated by all of the tested growth factors. For cells raised in a serum-free medium, only the nerve growth factor was ineffective. IMR32 cells, however, were unaffected by most of these growth factors, regardless of the medium conditions. Ethanol blocked the action of all growth factors tested. In general, all cells expressed the specific receptors for the six growth factors. Only the expression of the basic fibroblast growth factor, insulin-like growth factor-I, and nerve growth factor receptors were reduced by ethanol exposure. In summary, neuroblastoma cells exhibit differential susceptibility to ethanol, and this correlates with their response to mitogenic growth factors. Some growth factors are a target of ethanol toxicity. These heterogeneous effects seem to parallel ethanol-induced changes of proliferating neuronal precursors in vivo.
Alcohol Clin Exp Res 1997 Oct
PMID:Differential sensitivity of human neuroblastoma cell lines to ethanol: correlations with their proliferative responses to mitogenic growth factors and expression of growth factor receptors. 934 77

Human neuroblastoma cells were exposed to ethanol (EtOH; 100 mM) in culture for various time periods. It was found that chronic EtOH exposure increased the arachidonyl-specific phospholipase A2 (PLA2) activity significantly in both cytosol (1.6-fold) and membrane (2.2-fold) fractions when 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine was used as a substrate. This arachidonyl-specific PLA2 activity progressively increased with increasing duration of EtOH exposure and reached peak level at 72-hr EtOH exposure (chronic). A significant amount of the PLA2 activity was associated with the membrane fraction. No significant difference in PLA2 activity was observed when 1-palmitoyl-2 oleoyl or linoleoyl-sn-glycero-3-phosphocholine was used as a substrate. It was also found that co-treatment of neuroblastoma cells with ganglioside GM1 reduced the EtOH-induced activation of arachidonyl-specific PLA2 activity. The present results indicate that arachidonic acid-specific PLA2 may play a role in adaptation mechanisms to chronic EtOH in cultured neuroblastoma cells. Ganglioside GM1, in part, may exert its neuroprotective effects by modulating arachidonyl-specific PLA2 activity in chronic EtOH-exposed neuroblastoma cells.
Alcohol Clin Exp Res 1997 Oct
PMID:Activation of arachidonic acid-specific phospholipase A2 in human neuroblastoma cells after chronic alcohol exposure: prevention by GM1 ganglioside. 934 79

In vivo studies show (a) that early exposure to ethanol depletes neurons in the central nervous system (CNS) and (b) that a primary target of ethanol in the developing nervous system is proliferating neuronal precursors. We used a neuronal cell line (B 104 neuroblastoma cells) as an in vitro model for the effects of ethanol on the proliferation of neuronal precursors to test the hypothesis that ethanol interferes with growth factor-regulated proliferation of neuron-like precursors. The effects of ethanol on the mitogenic activity of two growth factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor AA and BB (PDGF-AA and PDGF-BB), were examined. Cell proliferation was monitored by tracing the change in the numbers of cultured cells over 4-5 days and in the cell cycle kinetics was determined using a cumulative labeling technique with bromodeoxyuridine (BrdU). Western immunoblots and immunohistochemical preparations show that B104 cells expressed the high affinity receptors for bFGF, PDGF-AA and PDGF-BB. The three growth factors were potent mitogens for the B104 cells; they promoted an increase in cell number even when the cells were grown in serum-free medium. Ethanol depressed the bFGF-, PDGF-AA- and PDGF-BB-mediated cell proliferation without altering the incidence of cell death. These changes in proliferation were concentration-dependent; at a concentration of 100 mg/dl, ethanol partially, but significantly inhibited growth factor-stimulated proliferation and higher ethanol concentrations (400 mg/dl or more) completely abolished growth factor-regulated cell proliferation. The effects of ethanol on cell growth were a result of ethanol-induced changes in growth factor-regulated cell cycle kinetics, principally the total length of the cell cycle and the fraction of the population that was actively cycling (the growth fraction). Ethanol completely negated the action of bFGF, but only partially blocked PDGF-promoted cycling activity. Thus, B104 cells are a suitable model for studying the effects of ethanol on neuronal proliferation. The blockage of bFGF- and PDGF-mediated cell proliferation by ethanol supports the hypothesis that growth factors are a target of ethanol neurotoxicity. Furthermore, the differential actions and effects of ethanol on the two growth factors mirror effects observed in vivo.
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PMID:Basic fibroblast growth factor- and platelet-derived growth factor-mediated cell proliferation in B104 neuroblastoma cells: effect of ethanol on cell cycle kinetics. 937 13

This study compared the interaction between ethanol and gamma-aminobutyric acid (GABA)-mediated current responses elicited in several immortalized cell lines and stably transfected cells, as well as in cultured and acutely dissociated rat cerebellar Purkinje cells. Only cell lines that were found previously to possess functional GABAA receptors were examined in this study. Under identical recording conditions, ethanol (10-200 mM) exerted no effect on GABA-induced currents in any of the cell lines or stably transfected cells tested in this study. However, GABA responses monitored in both primary culture and acutely dissociated Purkinje cells were significantly potentiated by ethanol (25 and 50 mM). Mouse pancreatic cells (RINm5F) were insensitive to both diazepam and ethanol suggesting the expression of a GABAA receptor isoform lacking a gamma subunit. Immortalized neuroblastoma IMR-32 cells displayed GABA responses that could be distinguished based on differential sensitivity to diazepam. However, none of the IMR-32 cells displayed GABA responses that were sensitive to modulation by ethanol. GABA responses in the stably transfected cell lines, PA3 (alpha1beta1gamma2L) and WSS-1 (alpha1beta2gamma2), were also unaffected by exposure to ethanol. In Purkinje cells acutely dissociated from the neonatal cerebellum, the ethanol-induced potentiation of GABA-induced current response could be observed before postnatal day 7, when only the gamma2S but not the gamma2L splice variant is expressed. This indicates that the gamma2L subunit is not necessary for an ethanol-induced potentiation of GABAA receptor-mediated response to become manifest. In addition, the results point to inherent differences that should be taken into account in interpreting comparative data between native and recombinant GABAA receptors.
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PMID:Ethanol-GABAA receptor interactions: a comparison between cell lines and cerebellar Purkinje cells. 945 26

For a study of the underlying mechanisms of a possible interaction between ethanol and nicotinic receptors during ethanol dependence, the aim of this work was to investigate the effect of chronic ethanol exposure on nicotinic receptor subtypes in a transfected fibroblast cell line (M10 cells) stably expressing alpha4beta2 nicotinic receptor subtype and an SH-SY5Y neuroblastoma cell line expressing alpha3, alpha5, alpha7, beta2, and beta4 nicotinic acetylcholine receptor (nAChR) subunits. A significant dose-related decrease (-30-80%) in number of [3H]nicotine binding sites was observed in ethanol-treated (25-240 mM) compared with untreated M10 cells. Similarly, 4-day treatment with ethanol in concentrations relevant to chronic alcoholism (100 mM) decreased the number of nicotinic receptor binding sites in the SH-SY5Y cells when measured using [3H]epibatidine. When M10 cells were chronically treated with nicotine, ethanol partly inhibited the up-regulation of nicotinic receptors when present in the cells together with nicotine. Chronic treatment for 4 days with 100 mM ethanol significantly decreased the mRNA level for the alpha3 nAChR subunit (-39%), while the mRNA levels for the alpha7 (+30%) and alpha4 (+22%) subunits were significantly increased. Chronic ethanol treatment did not affect the mRNA levels for the beta2 nAChR subunit. Changes in the levels of nAChR protein and mRNA may have adaptive significance and be involved in the development of dependence, tolerance, and addiction to chronic ethanol and nicotine exposure. They also may be targets for therapeutic strategies in the treatment of ethanol and nicotine dependence.
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PMID:Chronic ethanol treatment decreases [3H]epibatidine and [3H]nicotine binding and differentially regulates mRNA levels of nicotinic acetylcholine receptor subunits expressed in M10 and SH-SY5Y neuroblastoma cells. 948 34

An isomaltotriose-producing endo-dextranase was simply purified from cell-free culture broth of a Fusarium sp. by ethanol fractionation and consecutive column chromatographies using DEAE-Toyopearl and Bio-Gel P-100. The purified enzyme was judged to be homogeneous on PAGE and SDS-PAGE as well as isoelectric focusing. The molecular mass of the enzyme was estimated to be about 69 kDa by SDS-PAGE. The enzyme is an acidic protein with a pI of 4.6. The optimum pH and temperature were pH 6.5 and 35 degrees C, respectively. The enzyme was completely stable over the range of pH 4.5-11.8 at 4 degrees C for 24 h and at temperatures below 45 degrees C. Inactivation of the enzyme was found to be partial with 5 mM Cu2+, being about 70% inhibition and complete with 5 mM of Fe3+, Hg2+, Ag+ or NBS. The enzyme split dextran in an endo-lytic action to produce a large amount of isomaltotriose and a slight amount of isomaltose and glucose. The anomeric configurations of the reaction products formed by the enzyme were alpha-form, indicating that the alpha-glycoside linkages in the substrate are retained. The final yield of isomaltotriose from dextran T-2000 was about 62%.
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PMID:Purification and characterization of an isomaltotriose-producing endo-dextranase from a Fusarium sp. 950 22

Muscarinic receptor stimulation and activation of protein kinase C cause an increase in fosB and junB transcripts in human neuroblastoma SH-SY5Y cells. In this study, the effect of long-term ethanol exposure on these events was investigated. Carbachol-stimulated fosB and junB expression was elevated in ethanol-exposed cells compared with control cells. The potentiation was time- and dose-dependent on ethanol. Preincubation with muscarinic antagonists or protein kinase C inhibitor demonstrated that the carbachol-stimulated increase in fosB and junB mRNA levels was primarily mediated via M1 receptors and dependent on the activity of protein kinase C in both control and ethanol-exposed cells. Long-term ethanol exposure did not influence the expression of fosB and junB induced by activation of protein kinase C with phorbol ester. These results demonstrate that the muscarinic receptor-stimulated fosB and junB expression is sensitive to ethanol exposure in SH-SY5Y cells, suggesting that these genes participate in the regulation of neuronal function in response to chronic ethanol treatment.
Alcohol Clin Exp Res 1998 Feb
PMID:Ethanol exposure potentiates fosB and junB expression induced by muscarinic receptor stimulation in neuroblastoma SH-SY5Y cells. 951 11

1. 5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to analyse effects of alcohols on receptor-channel kinetics in detail. 2. Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20-80% rise time and measured desensitization rate of the current induced by low concentrations (1-2 microM) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had similar effects on the 5-HT3 receptor-induced current. 3. TCEt and ButOH decreased the measured desensitization rate of current induced by 10 microM 5-HT, a maximally effective concentration of agonist. These alcohols also increased the relative amplitude of steady state to peak current induced by 2 or 10 microM 5-HT, indicating a possible decrease in the intrinsic rate of desensitization. 4. TCEt also decreased the deactivation rate of the current activated by 2 microM 5-HT after a short pulse of agonist application. 5. Current sweeps generated by 1 microM 5-HT in the presence or absence of 10 mM TCEt or 100 mM EtOH were well fitted using a modified standard kinetic model derived from the nicotinic acetylcholine receptor. This analysis indicated that potentiation by alcohols could be accounted for by increases in the association rate constant coupled with decreases in the dissociation and desensitization rate constants. 6. This study suggests that alcohols potentiate 5-HT3 receptor-mediated current by both increasing the rate of channel activation and stabilizing the open state by decreasing the rates of channel deactivation and desensitization.
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PMID:Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state. 951 97

The mechanism of the fetal embryopathology resulting from ethanol ingestion during pregnancy is not established. This review summarizes recent research on the interaction of ethanol and vitamin A in models that explore if an interaction between these two compounds might potentially be the mechanism for fetal alcohol syndrome. The rationale for this hypothesis includes the known facts that: (1) in adults, ethanol ingestion alters vitamin A metabolism and tissue distribution; (2) there are many phenotypic similarities between fetal alcohol syndrome and malformations of both vitamin A toxicity and deficiency; and (3) the vitamin A metabolite, retinoic acid (RA), is a potent mediator in embryogenesis and differentiation. One interaction that could possibly alter fetal development is that the synthesis of RA from retinol, catalyzed by alcohol dehydrogenase, might be competitively inhibited by ethanol leading to RA deficiency. Controversy over this hypothesis continues. Another model demonstrates in vivo effects of pregnant rat mother's ethanol consumption on retinol, retinyl ester, RA content, RA receptor (RAR) binding, and the levels of RAR expression in developing fetal organs. The variable responses in this model still need clarification, and specific defects resulting from specific RAR changes have not yet been identified. In a quail embryo model, ethanol treatment mimics vitamin A deficiency, and RA appears to prevent the adverse effects of ethanol. Finally, RA and ethanol reverse or block each other's effects in studies on isolated neuroblastoma cells. Taken together, these experiments show definite interactions between ethanol and vitamin A. Further studies are needed to determine if any of these mechanisms significantly contribute to prenatal ethanol consumption embryopathy; but, clearly this hypothesis is gaining experimental support.
Alcohol Clin Exp Res 1998 Oct
PMID:The interaction of ethanol and vitamin A as a potential mechanism for the pathogenesis of Fetal Alcohol syndrome. 980 41


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