Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Chronic treatment of neuroblastoma X glioma hybrid cells (NG 108-15) with the muscarinic cholinergic agonist carbachol, which acutely inhibits adenylate cyclase, resulted in a 104 +/- 10% increase in PGE1-stimulated cAMP accumulation. Pretreatment of intact cells with pertussis toxin can structurally modify the inhibitory regulatory protein, Gi, by ADP-ribosylation and thus abolish the acute inhibition by carbachol. Pretreatment of the cells with pertussis toxin also resulted in a 27 +/- 8% increase in PGE1-stimulated cAMP accumulation. In the pertussis toxin-treated cells, chronic treatment with carbachol did not further enhance the PGE1 stimulation. These results suggest that functional Gi is required for the development of muscarinic cholinergic-induced enhancement of PGE1-stimulated cAMP accumulation.
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PMID:Muscarinic cholinergic receptor-induced enhancement of PGE1-stimulated cAMP accumulation in neuroblastoma X glioma cells: prevention by pertussis toxin. 302 78

Amounts of the guanine nucleotide binding regulatory proteins which are also pertussis toxin substrates (such as Ni and No) were measured in rat glioma, C6BU-1, cells and in neuroblastoma X glioma, NG108-15, hybrid cells. Measurements were performed both by quantitating pertussis toxin catalyzed ADP-ribosylation and by quantitative immunoblotting with affinity purified antibodies specific for Ni or No. The amounts of pertussis toxin substrate in C6 and NG108-15 cells are 7.5 and 0.6 pmol/mg membrane protein, respectively. These levels are minimum values and higher estimates of the total amounts of N proteins in the two cells are obtained by quantitative immunoblot analysis of the beta-subunit common to all N proteins. Immunoblots with specific antibodies show that NG108-15 cells contain 3.8 pmol/mg of No and detectable but small (less than 0.1 pmol/mg) amounts of Ni. In contrast, C6 cell membranes contain no detectable No and only 0.14 pmol/mg Ni. Thus, C6 cells contain large amounts of a pertussis toxin substrate which is neither Ni nor No.
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PMID:The GTP-binding regulatory proteins of neuroblastoma x glioma, NG108-15, and glioma, C6, cells. Immunochemical evidence of a pertussis toxin substrate that is neither Ni nor No. 308 Mar 32

The culture medium of certain strains of Clostridium botulinum type C contains two separable ADP-ribosyltransferases. Besides the ADP-ribosylation of actin due to botulinum C2 I toxin, a second microbial enzyme causes the mono-ADP-ribosylation of a eukaryotic protein with a molecular mass of about 20 kDa found in platelets, neuroblastoma X glioma hybrid cells, S49 lymphoma cells, chick embryo fibroblasts and sperm. The eukaryotic substrate is inactivated by heating and trypsin treatment. In contrast, the novel ADP-ribosyltransferase, which can be separated by DEAE-Sephadex chromatography, is largely resistant in the short term to trypsin digestion.
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PMID:Clostridium botulinum type C produces a novel ADP-ribosyltransferase distinct from botulinum C2 toxin. 310 Mar 33

NG108-15 neuroblastoma x glioma hybrid cells express a major 45 kDa substrate for cholera toxin and a 40 kDa substrate(s) for pertussis toxin when ADP-ribosylation is performed in the presence of GTP. In the absence of exogenous GTP, however, cholera toxin was shown to catalyse incorporation of radioactivity into a 40 kDa protein as well as into the 45 kDa polypeptide. In membranes of cells which had been pretreated in vivo with pertussis toxin, the 40 kDa band was no longer a substrate for either pertussis or cholera toxin in vitro, whereas in membranes from cholera-toxin-pretreated cells the 40 kDa band was still a substrate for fresh cholera toxin in vitro and for pertussis toxin. In this cell line, opioid peptides have been shown to inhibit adenylate cyclase exclusively by interacting with Gi (inhibitory G-protein) and with no other pertussis-toxin-sensitive G-protein. Opioid agonists, but not antagonists, promoted the cholera-toxin-catalysed ADP-ribosylation of the 40 kDa polypeptide, hence demonstrating that this cholera-toxin substrate was indeed the alpha-subunit of Gi. These results demonstrate that Gi can be a substrate for either cholera or pertussis toxin under appropriate conditions.
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PMID:Opioid peptides promote cholera-toxin-catalysed ADP-ribosylation of the inhibitory guanine-nucleotide-binding protein (Gi) in membranes of neuroblastoma x glioma hybrid cells. 313 27

The major pertussis-toxin-sensitive guanine nucleotide-binding protein of rat glioma C6 BU1 cells corresponded immunologically to Gi2. Antibodies which recognize the alpha subunit of this protein indicated that it has an apparent molecular mass of 40 kDa and a pI of 5.7. Incubation of membranes of these cells with guanosine 5'-[beta gamma-imido]triphosphate, or other analogues of GTP, caused release of this polypeptide from the membrane in a time-dependent manner. Analogues of GDP or of ATP did not mimic this effect. The GTP analogues similarly caused release of the alpha subunit of Gi2 from membranes of C6 cells in which this G-protein had been inactivated by pretreatment with pertussis toxin. The beta subunit was not released from the membrane under any of these conditions, indicating that the release process was a specific response to the dissociation of the G-protein after binding of the GTP analogue. Similar nucleotide profiles for release of the alpha subunits of forms of Gi were noted for membranes of both the neuroblastoma x glioma hybrid cell line NG108-15 and of human platelets. These data provide evidence that: (1) pertussis-toxin-sensitive G-proteins, in native membranes, do indeed dissociate into alpha and beta gamma subunits upon activation; (2) the alpha subunit of 'Gi-like' proteins need not always remain in intimate association with the plasma membrane; and (3) the alpha subunit of Gi2 can still dissociate from the beta/gamma subunits after pertussis-toxin-catalysed ADP-ribosylation.
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PMID:GTP analogues promote release of the alpha subunit of the guanine nucleotide binding protein, Gi2, from membranes of rat glioma C6 BU1 cells. 314 Aug 1

The GTP-activated Ca2+ release process we recently described (Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W. (1986) Nature 320, 461-464) was revealed in the preceding report to operate via a mechanism likely to be induced by close membrane association but which appears not to involve membrane fusion (Chueh, S. H., Mullaney, J. M., Ghosh, T. K., Zachary, A. L., and Gill, D. L. (1987) J. Biol. Chem. 262, 13857-13864). To determine more about the GTP-activated Ca2+ translocation process, effects of GTP on cells loaded with Ca-oxalate were investigated. Using permeabilized cells of both the N1E-115 neuroblastoma and DDT1MF-2 smooth muscle cell lines, 10 microM GTP activates a profound uptake of Ca2+ in the presence of oxalate, as opposed to release observed without oxalate. GTP stimulation of Ca2+ uptake was observed at oxalate concentrations (2 mM) only slightly augmenting Ca2+ uptake without GTP; with 8 mM oxalate (which alone induces linear Ca2+ accumulation) GTP still increases the rate of uptake. GTP-activated uptake in the presence of oxalate is completely reversed by 1 mM vanadate. 3% polyethylene glycol enhances the effect of GTP although GTP-activated uptake is still observed without polyethylene glycol. The Km for GTP for activation of Ca2+ uptake is 0.9 microM. Uptake is not activated by guanosine 5'-O-(3-thio)triphosphate (GTP gamma S) or guanosine 5'-(beta, gamma-imido)triphosphate (GppNHp); however, GTP gamma S (but not GppNHp) completely blocks the action of GTP. GDP gives a delayed uptake response which is blocked by ADP, indicating its action arises from conversion to GTP. In the presence of ADP, GDP blocks the action of GTP; guanosine 5'-O-(2-thio)diphosphate, which does not activate uptake, also blocks the action of GTP. These data reveal almost exact correlation between parameters affecting GTP-activated uptake and release, strongly suggesting the same process mediates both events. To explain the opposite effects of GTP in the absence and presence of oxalate, it is proposed that GTP activates a transmembrane conveyance of Ca2+ between oxalate-permeable and -impermeable compartments.
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PMID:Intracellular calcium uptake activated by GTP. Evidence for a possible guanine nucleotide-induced transmembrane conveyance of intracellular calcium. 365 40

Ticlopidine (250 mg twice daily) was administered to human volunteers for seven days and the response of their heparinized platelet-rich plasma to SKNMC (ADP-dependent) human neuroblastoma cells was examined. The first wave of platelet aggregation, characteristic of ADP-dependent human tumor cell lines, was completely abolished but was replaced by a lag period prior to the onset of aggregation. In the Baumgartner perfusion apparatus there was a marked inhibition in the thrombus generated by the presence of SKNMC cells with a concomitant increase in the percentage of surface coverage. These results suggest that the administration of ticlopidine could be useful to prevent some of the steps of metastatic dissemination in which activated platelets may play a role.
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PMID:Platelet activation induced by a human neuroblastoma tumor cell line is reduced by prior administration of ticlopidine. 375 Feb 63

The Baumgartner perfusion apparatus has been used for quantitative comparison of the interaction of platelets with subendothelium in the presence of microvesicles derived from SKNMC (human neuroblastoma) cells, which aggregate platelets by an adenosine diphosphate (ADP)-dependent mechanism, and U87MG (human glioblastoma) cells, which function by a thrombin-dependent mechanism. The derived microvesicles from each line were as effective as the intact cells in inducing thrombogenesis on both undigested and alpha-chymotrypsin-digested subendothelium. Thrombus size on digested vessels was greater than on undigested vessels by fivefold for SKNMC cells and microvesicles and by 20-fold for U87MG cells and sevenfold for U87MG microvesicles. The results show that microvesicles from both cell lines initiate interactions between platelets and subendothelium identical to those caused by intact tumor cells. The results also demonstrate that intact tumor cells in the circulation may not be necessary for the thromboembolic complications of malignancy.
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PMID:Morphometric evaluation of thrombogenesis by microvesicles from human tumor cell lines with thrombin-dependent (U87MG) and adenosine diphosphate-dependent (SKNMC) platelet-activating mechanisms. 378 31

Inhibitory coupling of receptors to adenylate cyclase previously has been shown to be relatively sensitive to inactivation by alkylation with N-ethylmaleimide (NEM). Modification of the inhibitory guanine nucleotide regulatory protein, Ni, has been proposed to be responsible for this effect. The effects of NEM on GTP-sensitive binding of carbachol to muscarinic cholinergic receptors has been compared in a cell line (1321N1 human astrocytoma cells) in which these receptors stimulate phosphoinositide breakdown and in a cell line (NG108-15 neuroblastoma X glioma cells) in which activation of these receptors results in inhibition of adenylate cyclase. Pretreatment of membrane preparations from 1321N1 cells with NEM resulted in a concentration-dependent decrease in the extent of pertussis toxin-catalysed [32P]ADP-ribosylation of a 41 000 Da protein previously proposed to be the alpha subunit of Ni. Under conditions where 32P-labelling of Ni in 1321N1 membranes was reduced by NEM by 90%, no effect was observed on the extent of guanine nucleotide-sensitive high-affinity binding of carbachol to muscarinic cholinergic receptors. In contrast, treatment of NG108-15 membranes with NEM under the same conditions resulted in complete loss of high-affinity guanine nucleotide sensitive binding of carbachol. These results illustrate another difference between the muscarinic receptor population of these two cell lines, and support the previous proposal that muscarinic receptors of 1321N1 cells couple to a guanine nucleotide regulatory protein that is not Ni.
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PMID:Further evidence that muscarinic cholinergic receptors of 1321N1 astrocytoma cells couple to a guanine nucleotide regulatory protein that is not Ni. 392 72

The effects of chelation of divalent cations in the interaction of platelets and tumor cells has been studied in a homologous human system using human platelet-rich plasma and two tumor cell lines of human origin: SKNMC (neuroblastoma) cells, which cause platelet aggregation by an adenosine diphosphate-dependent mechanism, and U87MG (glioblastoma) cells, which function by a thrombin-dependent mechanism. When added at zero time, citrate 14 mmol/L completely abolished aggregation in heparinized (5 U/ml) platelet-rich plasma by either cell line, but the degree of inhibition was reduced by later addition of the chelating agent. Calcium citrate 8 mmol/L reduced by only 10%, indicating that citrate anion was not responsible for the inhibition. Addition of Ca++ or Mg++ alone or in combination at concentrations up to 1.5 mmol/L did not reverse the inhibition. Addition of higher concentrations of Ca++ (2 mmol/L) caused immediate clotting, whereas concentrations of Mg++ up to 6 mmol/L were without effect. Inhibition could be reversed by washing the platelets free of citrate and resuspending in heparinized platelet-rich plasma. Aggregation by either cell line was inhibited by EDTA and EGTA. In the Baumgartner perfusion apparatus, platelet interaction with subendothelium was increased about 50-fold in the presence of SKNMC cells, but this effect was also abolished after addition of citrate. After addition of U87MG cells to heparinized PRP, there was a 400-fold increase in platelet interaction with subendothelium, and complex thrombi containing red cells, white cells, and fibrin were formed. This stimulation was reduced to control levels by addition of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of divalent cations on the interaction of platelets with tumor cells: aggregation and perfusion studies with two homologous human systems. 400 24


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