UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliosides, sialic acid-containing glycosphingolipids, enhance platelet adhesion to collagen and consequent platelet activation. For example, gangliosides shed by neuroblastoma tumor cells (NBTG) added to a subthreshold (non-activating) concentration (1 microgram/ml) of collagen, cause platelet aggregation (59 +/- 10%) and ATP release (2.3 +/- 0.2 nmol) equivalent to that caused by 10 micrograms/ml collagen alone. Here we report further studies to characterize this effect. Platelet aggregation and ATP release were not induced by NBTG in combination with subthreshold concentrations of adenosine diphosphate, epinephrine, thrombin or arachidonic acid, suggesting that NBTG specifically influences collagen-mediated platelet activation. Maximal platelet aggregation and ATP release required extracellular magnesium and only a short (1 min) preincubation with NBTG, suggesting a collagen receptor-mediated mechanism of this ganglioside activity. Since gangliosides interact with several integrin receptors, we determined whether NBTG influences alpha 2 beta 1, a major integrin collagen receptor on platelets. Incubation of platelets with a monoclonal antibody directed against the alpha 2 chain (5E8) blocked the increase in platelet aggregation (9 +/- 3% vs. 80 +/- 2%) and ATP release ( < 0.2 vs 2.5 +/- 0.1 nmol) induced by NBTG and 1 microgram/ml collagen. Incubation with an antibody to the non-integrin collagen receptor, CD36, or with an isotype control antibody did not abrogate the effect of NBTG. Finally, NBTG and its major component, GD2, enhanced alpha 2 beta 1-mediated platelet adhesion to immobilized collagen in an antibody 5E8-inhibitable manner. These findings implicate the alpha 2 beta 1-collagen interaction as a target of the effect of tumor-derived gangliosides.
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PMID:Tumor gangliosides enhance alpha2 beta1 integrin-dependent platelet activation. 863 39

The homodimeric SecA protein is the peripheral subunit of the preprotein translocase in bacteria. It binds the preprotein and promotes its translocation across the bacterial cytoplasmic membrane by nucleotide modulated coinsertion and deinsertion into the membrane. SecA has two essential nucleotide binding sites (NBS; Mitchell & Oliver, 1993): The high-affinity NBS-I resides in the amino-terminal domain of the protein, and the low-affinity NBS-II is localized at 2/3 of the protein sequence. The nucleotide-bound states of soluble SecA were studied by site directed tryptophan fluorescence spectroscopy, tryptic digestion, differential scanning calorimetry, and dynamic light scattering. A nucleotide-induced conformational change of a carboxy-terminal domain of SecA was revealed by Trp fluorescence spectroscopy. The Trp fluorescence of a single Trp SecA mutant containing Trp775 decreased and increased upon the addition of NBS-I saturating concentrations of ADP or AMP-PNP, respectively. DSC measurements revealed that SecA unfolds as a two domain protein. Binding of ADP to NBS-I increased the interaction between the two domains whereas binding of AMP-PNP did not influence this interaction. When both NBS-I and NBS-II are bound by ADP, SecA seems to have a more compact globular conformation whereas binding of AMP-PNP seems to cause a more extended conformation. It is suggested that the compact ADP-bound conformation resembles the membrane deinserted state of SecA, while the more extended ATP-bound conformation may correspond to the membrane inserted form of SecA.
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PMID:Domain interactions of the peripheral preprotein Translocase subunit SecA. 881 Sep 4

In neuroblastoma X glioma hybrid NG108-15 cells, P2 purinoceptor agonists inhibited forskolin-stimulated cyclic AMP accumulation with distinct selectivities and their activities could be partially reversed by P2 purinoceptor antagonists. The rank order of potency in inhibition of cyclic AMP accumulation was UTP > 2 methylthio-ATP (MeSATP) > benzoylbenzoic ATP (BzATP) = alpha, beta-methylene ATP (AMPCPP) > beta, gamma-methylene ATP (AMPPCP) > ATP > ADP > adenosine 5'-thiotriphosphate (ATP gamma S). Neither adenosine nor AMP caused any inhibitory effect on cyclic AMP accumulation. Pertussis toxin treatment of cells attenuated the inhibitory effect of UTP, MeSATP and ATP on cyclic AMP accumulation whereas it had no effect on the BzATP-induced response. In addition, P2-purinoceptor-mediated inhibition of cyclic AMP accumulation was insensitive to cytosolic Ca2+ concentration. The breakdown of cyclic AMP was enhanced by MeSATP but not by the addition of ATP, UTP and BzATP. Our results suggest that a pertussis toxin-sensitive Gi signalling pathway is directly coupled to the occupancy of P2u and P2y receptors in NG108-15 cells.
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PMID:P2 purinoceptor-mediated inhibition of cyclic AMP accumulation in NG108-15 cells. 889 31

Chronic exposure of all-trans-retinoic acid-differentiated SH-SY5Y cells to morphine (10 mu M; 2 days) results in sensitization of adenylate cyclase as characterized by a significant increase in both PGE1 receptor-mediated as well as receptor-independent (NaF, 10 mM; forskolin, 100 mu M) stimulation of effector activity. To investigate the underlying biochemical alterations, chronic opioid regulation of each of the components comprising the stimulatory PGE1 receptor system was examined. On receptor level, chronic morphine treatment was found to reduce PGE1 receptor number (Bmax) by approximately 40%, whereas their affinity slightly increased. Binding experiments performed in the presence of GTPgammaS (100 mu M) further indicate that the decrease in PGE1 receptor density is associated with a loss of functionally G protein-coupled receptors. On post-receptor level, chronic morphine treatment substantially increased the abundance and functional activity of stimulatory G proteins, as assessed by cholera toxin-catalyzed ADP-ribosylation of GSalpha and S49 cyc- reconstitution assays. No changes were found on the level of adenylate cyclase. Evaluation of the functional interaction between PGE1 receptors and GS in situ by application of a C-terminal anti-GSalpha antibody revealed a more intense coupling efficiency between these two entities, since a significant higher amount of antibody (2.3-fold) was required in morphine dependent cell membranes to half-maximally attenuate PGE1 receptor-stimulated adenylate cyclase activity. In addition, limitation of the amount of functionally available GSalpha within the PGE1 receptor/adenylate cyclase signal transduction cascade abolished the generation of a supersensitive adenylate cyclase response during the state of naloxone (100 mu M)-precipitated withdrawal. These data demonstrate that in human neuroblastoma SH-SY5Y cells chronic morphine-induced sensitization of adenylate cyclase is associated with distinct quantitative and qualitative adaptations within the stimulatory adenylate cyclase-coupled PGE1 receptor system. Thus, alterations in the functional activity of stimulatory receptor systems are suggested to contribute to the cellular mechanisms underlying opioid dependence.
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PMID:Morphine dependence in human neuroblastoma SH-SY5Y cells is associated with adaptive changes in both the quantity and functional interaction of PGE1 receptors and stimulatory G proteins. 891 1

To clarify the mechanisms of nitric oxide (NO)-induced cell death in human neuronal cells, we examined effects of NO donors such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) on activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and poly(ADP-ribose) polymerase (PARP) in human neuroblastoma cell line, SH-SY5Y. SNP-induced [32P]ADP-ribosylation of 113-kDa and 37-kDa proteins in SH-SY5Y cells. Treatment with PARP inhibitors such as 3-aminobenzamide and 1,5-isoquinolinediol partially prevented SNAP-induced cell death of SH-SY5Y. In purified GAPDH (37-kDa protein), SNP- and SNAP-induced enhancement of [32P]ADP-ribosylation, and inhibition of GAPDH activity. These results suggest that NO-induced cell death in human neuroblastoma SH-SY5Y cells possibly involves in covalent modifications such as ADP-ribosylation in PARP and GAPDH.
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PMID:Possible involvement of ADP-ribosylation of particular enzymes in cell death induced by nitric oxide-donors in human neuroblastoma cells. 904 62

SecA is the peripheral subunit of the preprotein translocase of Escherichia coli. SecA consists of two independently folding domains, i.e., the N-domain bearing the high-affinity nucleotide binding site (NBS-I) and the C-domain that harbors the low-affinity NBS-II. ATP induces SecA insertion into the membrane during preprotein translocation. Domain-specific monoclonal antibodies (mAbs) were developed to analyze the functions of the SecA domains in preprotein translocation. The antigen binding sites of the obtained mAbs were confined to five epitopes. One of the mAbs, i.e., mAb 300-1K5, recognizes an epitope in the C-domain in a region that has been implicated in membrane insertion. This mAb, either as IgG or as Fab, completely inhibits in vitro proOmpA translocation and SecA translocation ATPase activity. It prevents SecA membrane insertion and, more strikingly, reverses membrane insertion and promotes the release of SecA from the membrane. Surface plasmon resonance measurements demonstrate that the mAb recognizes the ADP- and the AMP-PNP-bound state of SecA either free in solution or bound at the membrane at the SecYEG protein. It is concluded that the mAb actively reverses a conformation essential for membrane insertion of SecA. The other mAbs directed to various epitopes in the N-domain were found to be without effect, although all bind the native SecA. These results demonstrate that the C-domain plays an important role in the SecA membrane insertion, providing further evidence that this process is needed for preprotein translocation.
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PMID:Inhibition of preprotein translocation and reversion of the membrane inserted state of SecA by a carboxyl terminus binding mAb. 923 48

Incubation of Neuro 2A mouse neuroblastoma cells with UTP and UDP results in a concentration-dependent increase in the accumulation of inositol phosphates with equal potency and maximal effect; ATP, ADP, and 2-methylthioadenosine 5'-triphosphate were much less potent, indicating the expression of P2Y receptor in these cells. The effects of UTP and ATP were not affected by pretreatment of cells with pertussis toxin, indicating that the P2Y receptor in Neuro 2A cells is coupled to pertussis toxin-insensitive Gq protein. Short-term (10 min) treatment of cells with 1 microM 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in the inhibition of the UTP and ATP effects; this inhibitory effect was gradually attenuated with increased length of TPA treatment (1.5-6 h) and was not seen after long-term (24 h) treatment. Western blot analysis showed the expression of protein kinase C (PKC) alpha, epsilon, theta, and zeta in Neuro 2A cells. Translocation of PKC alpha, epsilon, and theta from the cytosol to the membrane was seen after 10 min or 1.5 h of treatment with TPA. However, partial and complete down-regulation of both membrane PKC alpha and theta were seen after 3 and 6 h of treatment, respectively. In contrast, the TPA-induced translocation of PKC epsilon was maintained after 3-6 h of treatment, and almost complete down-regulation occurred only after a 24-h treatment. The observed TPA-induced inhibition of UTP- or ATP-stimulated phosphoinositide hydrolysis, therefore, correlated well with the extent of translocation of PKC epsilon. Phosphoinositide hydrolysis induced by AlF4-, but not Ca2+ ionophores, was inhibited by a 10-min treatment with TPA. This was not seen after a 24-h treatment, indicating that the site of action of PKC epsilon in the P2Y receptor/Gq protein/phospholipase C beta pathway might be the Gq protein. This is the first study to show the existence of the P2Y receptor in Neuro 2A cells and the possible involvement of neuronal PKC epsilon in the regulation of the receptor-mediated phosphoinositide turnover.
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PMID:P2Y receptor linked to phospholipase C: stimulation of neuro 2A cells by UTP and ATP and possible regulation by protein kinase C subtype epsilon. 932 69

On the cellular level, opioid dependence is characterized by a significant elevation of adenylyl cyclase (AC) activity after drug withdrawal, a regulatory phenomenon termed "AC supersensitivity" or "cAMP overshoot." The present study examines the role of the stimulatory G protein (Gs) in the expression of naloxone precipitated opioid withdrawal in chronically morphine (10 microM; 3 days) treated neuroblastoma X glioma (NG108-15) hybrid cells. Determination of high-affinity [3H]forskolin binding to intact cells, which provides a direct parameter for the binding of the activated alpha-subunit of Gs (Gsalpha) to AC, revealed that the enhancement of AC activity after opioid withdrawal is not caused by an increased stimulation of effector activity by Gsalpha. Although not a direct function of Gs, the expression of AC supersensitivity required Gsalpha-mediated stimulation of AC, because 1) the enhancement of AC activity after opioid withdrawal was observed only in the presence of low, but not of high concentrations of forskolin, and 2) chemical inactivation of Gsalpha by low pH pretreatment abolished the induction of AC supersensitivity. Moreover, the regulatory mechanism underlying AC supersensitivity not only required the presence of activated Gsalpha per se, but functional intact stimulatory signal transduction pathways. Indeed, blockade of prostaglandin E1 receptor/Gs interaction in situ with a site-specific anti-Gsalpha antibody, as well as uncoupling of prostaglandin E1 receptor signaling by cholera toxin-catalyzed ADP-ribosylation of Gsalpha, prevented the expression of AC supersensitivity in membranes from opioid-withdrawn cells. These results suggest that the enhancement of AC activity in opioid-dependent cells, triggered by drug withdrawal, is not a direct Gsalpha effect, but involves a secondary regulatory event that requires costimulation of AC by acutely receptor-activated Gsalpha.
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PMID:Adenylyl cyclase supersensitivity in opioid-withdrawn NG108-15 hybrid cells requires Gs but is not mediated by the Gsalpha subunit. 969 42

Regulation of inositol phospholipid hydrolysis by UTP and UDP in neuroblastoma x glioma hybrid cell line NG108-15 was potentiated in the presence of ATP. The effect of ATP was dose dependent and shifted the EC50 value for these uracil nucleotides up to three powers of magnitude, having no influence on the maximal value of the response. Adenine nucleotides (ADP, AMP, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), beta,gamma-methyleneadenosine 5'-triphosphate (betagammaMeATP), 3'-O-(4-benzoyl)benzoyl ATP (BzATP) and 3'-deoxyadenosine 5'-O-(1-thio)triphosphate (dATPalphaS)) as well as adenosine, had no influence on the pyrimidinoceptor response. The potentiation effect was abolished by excess of EDTA. The results were in agreement with the hypothesis of pyrimidinoceptor affinity regulation via extracellular phosphorylation of the receptor protein, initiated by ATP. This mechanism may have physiological implication for functioning of uracil nucleotides as endogenous signaling molecules.
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PMID:Pyrimidinoceptor potentiation by ATP in NG108-15 cells. 984 88

Glial cell line-derived neurotrophic factor (GDNF) signals through a unique receptor system that includes Ret receptor tyrosine kinase and a glycosyl-phosphatidylinositol-linked cell surface protein. In the present study, we have identified several proteins in neuroblastoma cells that are phosphorylated on tyrosine in response to GDNF. The phosphorylated proteins include focal adhesion kinase (FAK), paxillin and Crk-associated substrate, p130Cas, all of which are known to be associated with focal adhesions. Of these, paxillin and p130Cas interacted with Crk proteins in GDNF-treated neuroblastoma cells. GDNF also induced reorganization of the actin cytoskelton. Tyrosine phosphorylation of FAK, paxillin and p130Cas was inhibited by cytochalasin D or two specific inhibitors of phosphatidylinositol-3' kinase (PI-3' kinase), wortmannin and LY294002, indicating that their tyrosine phosphorylation depends on the formation of actin stress fiber and activation of PI-3' kinase. In addition, phosphorylation of FAK but not of paxillin and p130Cas was markedly impaired by the Clostridium botulinum C3 exoenzyme that specifically ADP-ribosylates and inactivates Rho. These results suggested the presence of Rho-dependent and -independent signaling pathways downstream of PI-3' kinase that mediate tyrosine phosphorylation of FAK, paxillin and p130Cas through Ret kinase.
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PMID:Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase, paxillin and p130Cas mediated by Ret kinase. 1020 19

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