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)

Nerve growth factor (NGF) induces a protein in the C1300 mouse neuroblastoma cell line which recognises the octamer DNA consensus sequence 'ATGCAAAT'. This protein is absent, or only minimally present, in C1300 cells prior to induction with NGF. This induced octamer binding protein is detectable by gel retardation analysis within 3 h of NGF treatment and increases progressively with 24 h and 72 h of exposure to NGF.
Brain Res Mol Brain Res 1992 Sep
PMID:An NGF-inducible octamer binding protein activity in a C1300 neuroblastoma cell line. 133 65

Insulin-like growth factors (IGF) I and II are polypeptides with both growth-promoting and insulin-like metabolic effects. The developmentally specific expression of IGF I and II in the nervous system implies a role for these growth factors in neuronal growth and differentiation. In the present study, we analyzed IGF and IGF receptor mRNA transcripts from two related human neuroblastoma cell lines, SH-SY5Y and SK-N-SH. These cell lines provide a good in vitro model of neuronal development. Northern analysis of total RNA from each cell line revealed three IGF II mRNA transcripts (6.0, 4.8, and 1.8 kb), and one mRNA transcript each for the type I (11.0 kb) and type II (9.4 kb) IGF receptors. The size distribution of these multiple transcripts is similar to that found during normal human fetal development. These results establish both cell lines as good in vitro models for investigating the mechanisms which underly IGF gene expression during nervous system development.
Brain Res Mol Brain Res 1992 Oct
PMID:Gene expression of the insulin-like growth factors and their receptors in human neuroblastoma cell lines. 133 80

Protein kinase C (PKC) activation was examined for its role in delta-opioid receptor down-regulation in the neuroblastoma X glioma hybrid cell line NG108-15. Incubation of NG108-15 cells for 2 hr at 37 degrees with up to 1 microM 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), a phorbol ester that activates PKC, had no effect on opioid binding to membranes prepared from these cells. However, as little as 3 nM PMA incubated with an opioid agonist and NG108-15 cells potentiated the decrease and the rate of decrease of opioid binding, compared with agonist alone. Scatchard analysis of [3H][D-Ala2,D-Leu5]enkephalin (DADLE) binding revealed that NG108-15 cells incubated for 3 hr with 1 nM DADLE and 30 nM PMA displayed a > 50% reduction in the number of [3H]DADLE binding sites with no affinity change at the remaining sites, compared with cells treated with DADLE alone. The antagonist naloxone blocked both DADLE-induced and PMA-enhanced DADLE-induced down-regulation. The agonists morphine and cyclazocine, which alone were unable to induce delta receptor down-regulation, did so in the presence of PMA. The PKC inhibitor staurosporine and down-regulation of PKC by chronic PMA treatment blocked PMA potentiation of DADLE-induced down-regulation, but not "normal" DADLE-induced down-regulation. The enhancement of down-regulation by PMA was unaffected by either metabolic inhibitor or incubations at 20 degrees, conditions that blocked down-regulation by DADLE alone. NG108-15 cells incubated with [3H]DADLE and PMA retained more [3H]DADLE than cells incubated with [3H]DADLE alone, suggesting that PMA enhanced receptor internalization instead of merely inhibiting membrane binding. The diacylglycerol 1-oleoyl-2-acetyl-glycerol and bradykinin substituted for PMA but not carbachol, indicating that PKC activated physiologically may play a role in delta receptor down-regulation.
Mol Pharmacol 1992 Oct
PMID:Protein kinase C activation increases the rate and magnitude of agonist-induced delta-opioid receptor down-regulation in NG108-15 cells. 133 57

The immortalized septal cell line, SN56 B5 G4, generated by the fusion of mouse septal area cells and neuroblastoma cells, was used to determine if nimodipine, an antagonist of voltage sensitive calcium 'L' channels, might act in a neuroprotective fashion when intracellular calcium levels were raised by incubation in ouabain and monensin. Fluorescent indicator dyes and the automated spectrofluorometer, the CytoFluor 2300, were used to analyze specific cellular targets and functions affected by ouabain and monensin and possible protection by prior incubation with nimodipine. Ouabain and monensin were used together to create a time- and dose-dependent toxic episode. Increases in the emission intensity of Fluo3-AM demonstrated that the concentration of intracellular calcium was monotonically increased by increasing levels of ouabain-monensin. The calcein-AM fluorescent probe indicated that there were no changes in plasma membrane permeability during the toxic episode. Lysosomal integrity decreased as indicated by decreases in neutral red retention. The concentration of free radicals increased as shown by the increase in emission intensity of 2',7'-dichlorfluorescein. Nimodipine pretreatment of the cells incubated with ouabain and monensin resulted in apparent protection of lysosomes and a reduction in the level of free radicals. While nimodipine, by itself, produced a small decrease in intracellular calcium, it actually augmented the ouabain-monensin induced increase in intracellular calcium. The data suggest that in immortalized septal cells, (a) nimodipine offers protection to certain of the responses induced by ouabain-monensin, (b) the protection offered by nimodipine may be independent of antagonism of voltage sensitive calcium channels, and (c) that the protective changes can occur at the same time that intracellular calcium is increasing. These latter observations question the hypothesis that the protection against cell death and dysfunction offered by nimodipine is due solely to maintaining calcium homeostasis.
Brain Res Mol Brain Res 1992 Nov
PMID:Cellular alterations produced by the experimental increase in intracellular calcium and the nature of protective effects from pretreatment with nimodipine. 133 95

Six independent clonal isolates from a morphologically heterogeneous human neuroblastoma cell line stably expressed several products of the human amyloid precursor protein (APP) from an introduced DNA construct; the "substrate-adherent" phenotype (fibroblast-like cells) predominated in all 6; these displayed immunoreactivity of vimentin, but little to no reactivity of neuron-specific enolase. A stably transfected isolate which did not show any expression from the identical construct (presumably because of a position effect) exhibited the predominantly neuronal phenotype of the parental cells (neuron-specific enolase positive). These results suggest selective neurotoxicity of the expressed products. Two of the 6 stably expressing cell lines showed a decrease of native mRNA for APP to levels that were 1/4-1/3 that of the parental cells and a decrease of their growth rates to half that of the parental cells; these decreased growth rates were improved by conditioned medium from the parental cell line. Western blot analysis revealed at least four distinct fragments of the COOH-terminus of APP in the isolate which expressed protein and mRNA in greatest abundance, suggesting that overexpression of APP in a human neural cell line leads to aberrant cleavage of APP.
Brain Res Mol Brain Res 1992 Nov
PMID:Expression of a carboxy-terminal region of the beta-amyloid precursor protein in a heterogeneous culture of neuroblastoma cells: evidence for altered processing and selective neurotoxicity. 133 98

The alkaloid pumiliotoxin B (PTX-B) "activates" voltage-dependent sodium channels in synaptoneurosomes and neuroblastoma cells. It appears that PTX-B activates sodium channels by interacting with a site that is allosterically coupled to other sites on the sodium channel, namely two scorpion toxin sites and the brevetoxin site. In guinea pig cortical synaptoneurosomes, alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin induce a dose-dependent potentiation of PTX-B-induced 22Na+ influx. The synergism with beta-scorpion toxin differentiates PTX-B from the alkaloid veratridine, which induces an activation of sodium channels that is not affected by beta-scorpion toxin. PTX-B does not inhibit [3H]batrachotoxinin-A benzoate ([3H]BTX-B) binding to the alkaloid site on sodium channels. On the other hand, aconitine, which activates sodium channels and inhibits [3H]BTX-B binding, induces a 22Na+ influx that, like PTX-B-induced 22Na+ influx, is potentiated by alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin. Inhibition of [3H]BTX-B binding by aconitine is reduced in the presence of PTX-B. Both a type I pyrethroid (allethrin) and a type II pyrethroid (fenvalerate) inhibit PTX-B- and PTX-B/alpha-scorpion toxin-mediated 22Na+ influx. Allethrin and fenvalerate also inhibit aconitine-mediated 22Na+ flux but not BTX-mediated 22Na+ influx. It is proposed that on the sodium channel there is an "alkaloid-binding domain" at which alkaloids exert stimulatory actions. However, depending on the region on the domain to which the binding occurs, different allosteric interactions with other sites can be observed. PTX-B is proposed to interact with a part of the alkaloid-binding domain that is shared by aconitine but not by batrachotoxin or veratridine, whereas aconitine interacts with a part of the domain shared by PTX-B and by batrachotoxin/veratridine.
Mol Pharmacol 1992 Dec
PMID:Interaction of pumiliotoxin B with an "alkaloid-binding domain" on the voltage-dependent sodium channel. 133 16

We have used the polymerase chain reaction (PCR) to detect amplification of the MYCN oncogene in neuroblastoma cell lines and to distinguish primary tumors with a single copy from those with MYCN amplification using DNA extracted from frozen sections. Two primer pairs were used to co-amplify a 428-bp fragment of the MYCN oncogene along with a 268-bp fragment of the beta-globin gene (a single-copy reference standard). After 30 cycles of PCR, the products were resolved by agarose gel electrophoresis. MYCN gene amplification was identified by visual comparison of the relative intensities of MYCN and beta-globin PCR product bands on the ethidium bromide-stained gel. This semiquantitative approach, while inadequate for precise determination of copy number, provided a simple, rapid, nonisotopic method for differentiating tumors with MYCN amplification from those with a single copy. Seventy-four primary tumors were classified as amplified or nonamplified by semiquantitative PCR. Twenty-two of 23 tumors known to carry MYCN gene amplification by Southern analysis were correctly identified by PCR. The single false-negative result was due to a sampling error: DNA was extracted from a block of tissue containing small foci of tumor surrounded by normal tissue. Fifty-one of 51 tumors with a single copy of MYCN were also correctly identified by PCR. We conclude that semiquantitative PCR is a reliable, non-isotopic alternative to Southern blotting for detection of MYCN gene amplification that can be performed rapidly on DNA extracted from frozen sections.
Diagn Mol Pathol 1992 Dec
PMID:Rapid detection of MYCN gene amplification in neuroblastomas using the polymerase chain reaction. 134 70

In SK-N-SH human neuroblastoma cells, the muscarinic agonist carbachol promotes polyphosphoinositide (PPI) hydrolysis via M3 receptors and increases cyclic AMP levels through an unidentified mechanism. Activation of PPI hydrolysis by carbachol elicits a robust translocation of CaM from membranes into cytosol which was previously shown to be mimicked by the addition of the calcium ionophore ionomycin and the phorbol ester TPA28. The effect of agonist-stimulated second messenger production on CaM localization was determined by activating receptors that increase and decrease adenylyl cyclase activity on SK-N-SH cells. VIP (10 microM), prostaglandin E1 (30 microM) and forskolin (10 microM) all increased adenylyl cyclase activity 8- to 10-fold above the activity with 1 microM GTP. Carbachol (100 microM) did not stimulate adenylyl cyclase activity. The alpha 2-adrenergic agonist UK 14,304 (0.1 microM) and the delta and mu opioid DPDPE (10 microM) and DAMGO (10 microM) inhibited forskolin-stimulated cyclic AMP formation by 27-32%. CaM did not stimulate adenylyl cyclase activity. Incubation of cells with vasoactive intestinal polypeptide (VIP), dibutyryl cyclic AMP and forskolin, resulted in 30% decrease in membrane CaM and an increase in cytosolic CaM of 40-50%. The CaM translocation with the combination of an agent that elevates cyclic AMP levels and a low dose of carbachol was not different from that observed with either agent alone. UK 14,304, DPDPE and DAMGO potentiated carbachol-stimulated increases in cytosolic CaM. Upon the addition of carbachol, a 5-fold increase in intracellular calcium concentration measured with fura-2 fluorescence was observed. VIP and UK 14,304 elevated intracellular calcium concentrations 2 to 3 fold, while forskolin (10 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Jan
PMID:Cyclic AMP accumulation alters calmodulin localization in SK-N-SH human neuroblastoma cells. 134 31

1. The expression of the gene codifying for CD4, the most important human immunodeficiency virus type 1 (HIV-1) receptor molecule, was analyzed in 11 fetal brains at various gestational ages and in 9 human neuroblastoma (NB) cell lines. CD4 gene expression in fetal and malignant neural cells was then compared with that observed in a hematopoietic cell line and adult hippocampus. 2. In addition, CD4 mRNA was evaluated in two NB cell lines induced to differentiate in vitro with retinoic acid (RA) or 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H7), a protein kinase C inhibitor. 3. All fetal brains and NB cell lines express a 1.8-kb signal when hybridized with pT4BcDNA probe, while a 3.0-kb signal such as observed in hematopoietic human cells was found in 1 of 11 fetal brains and in 0 of 9 NB cell lines. The 1.8-kb signal was lost in all analyzed poly(A)+ mRNA samples. 4. Moreover, CD4 gene expression was not induced in either RA- or H7-treated NB cells at any tested time and dose. The analysis of NB cells by polymerase chain reaction failed to demonstrate CD4 expression in either poly(A)+ or poly(A)- RNA. 5. In conclusion, the results show that the 1.8-kb signal observed in RNA extracted from fetal or transformed human neural cells is probably due to an aspecific hybridization. However, the gene codifying for CD4 can rarely be expressed by fetal brain cells early during gestation, in still unclear circumstances.
Cell Mol Neurobiol 1992 Apr
PMID:Analysis of CD4 gene expression in human fetal brain and neuroblasts. 135 Sep 44

Scrapie prions are composed largely, if not entirely, of the scrapie prion protein (PrPSc) that is encoded by a chromosomal gene. Scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells synthesize PrPSc from the normal PrP isoform (PrPC) or a precursor through a posttranslational process. In pulse-chase radiolabeling experiments, we found that presence of brefeldin A (BFA) during both the pulse and the chase periods prevented the synthesis of PrPSc. Removal of BFA after the chase permitted synthesis of PrPSc to resume. BFA also blocked the export of nascent PrPC to the cell surface but did not alter the distribution of intracellular deposits of PrPSc. Under the same conditions, BFA caused the redistribution of the Golgi marker MG160 into the endoplasmic reticulum (ER). Using monensin as an inhibitor of mid-Golgi glycosylation, we determined that PrP traverses the mid-Golgi stack before acquiring protease resistance. About 1 h after the formation of PrPSc, its N-terminus was removed by a proteolytic process that was inhibited by ammonium chloride, chloroquine, and monensin, arguing that this is a lysosomal event. These results suggest that the ER is not competent for the synthesis of PrPSc and that the synthesis of PrPSc occurs during the transit of PrP between the mid-Golgi stack and lysosomes. Presumably, the endocytic pathway features in the synthesis of PrPSc.
Mol Biol Cell 1992 Aug
PMID:Synthesis and trafficking of prion proteins in cultured cells. 135 22


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