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 expression of cellular adhesion molecules (CAM) involved in cell adhesion and immune recognition was measured on neuroblastoma tissue samples, on a neuroblastoma (NB) cell line, SK-N-SH, and on 3 phenotypically different variants, SH-SY5Y, SH-EP, SH-IN, representing neuronal, Schwannian/glial or intermediate NB-cell types. Immunohistochemical analysis of CAM expression by NB and related tumors at different stages of differentiation revealed a co-expression of several CAM (ICAM-1/CD54, LFA-3, VLA-2 and HLA-ABC) associated with low stages and more highly differentiated NB tumors and peripheral neuroepitheliomas (PN). In contrast, N-CAM was uniformly expressed on all NB tumors. Flow cytometric analysis of CAM surface expression by SK-N-SH and variant cells revealed highly variable phenotypes. Expression of ICAM-1, LFA-3, VLA-2 and HLA-ABC molecules was associated with the epithelial cell type represented by the SH-EP variant. In contrast, low expression of these molecules and high expression of N-CAM was associated with the neuronal SH-SY5Y cells. Exposure of the NB cells to differentiation inducers (retinoic acid, 5'-bromodeoxyuridine and phorbol esters) and cytokines (tau-interferon, alpha-tumor necrosis factor) resulted in a variable up-regulation of the expression of all CAMs, except N-CAM, regardless of the type of differentiation induced. In an attempt to establish a link between the pattern of expression of CAM on NB cells and their susceptibility to natural killer (NK) or lymphokine-activated killer (LAK) cell lysis, the analysis revealed that NB cells expressing CAM and a differentiated phenotype were less susceptible to NK lysis, but no difference in the sensitivity of the NB cell types to LAK effectors was observed. Treatment of NB target cells with cytokines or PMA decreased their susceptibility to NK and LAK lysis, while induction of differentiation with RA or BUdR resulted in no changes in the sensitivity to NK and LAK lysis. In conclusion, expression of HLA-ABC and several co-regulated CAMs was shown to be associated with a differentiated phenotype in NB, with an overall decreased sensitivity to NK/LAK effector cells.
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PMID:Differentiation-related expression of adhesion molecules and receptors on human neuroblastoma tissues, cell lines and variants. 135 3

Op18 is a highly conserved major cytosolic phosphoprotein that is expressed at high levels in acute leukemia and in neuroblastoma. In this study we present evidence pointing to a role for Op18 in cellular proliferation. Blocking of Op18 mRNA translation using antisense oligonucleotides delayed entrance of mitotically stimulated normal peripheral blood lymphocytes into the S phase. Moreover treatment of HL-60 promyelocytic leukemia cells with DMSO or PMA which induced terminal differentiation resulted in a decrease in the level of Op18 RNA and protein. Inhibition of lymphoid proliferation with cyclosporin also resulted in reduced Op18 levels.
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PMID:Involvement of OP18 in cell proliferation. 193 Feb 3

We have investigated the coupling of muscarinic acetylcholine receptors (mAChR) to phospholipid hydrolysis in a human neuroblastoma cell line, LA-N-2, by measuring the formation of 3H-inositol phosphates (3H-IP) and of [3H]phosphatidylethanol ([3H]PEt) in cells prelabeled with [3H]inositol and [3H]oleic acid. The muscarinic agonist carbachol (CCh) stimulated the phospholipase C (PLC)-mediated formation of 3H-IP in a time- and dose-dependent manner (EC50 = 40-55 microM). In addition, in the presence of ethanol (170-300 mM), CCh elevated levels of [3H]PEt [which is regarded as a specific indicator of phospholipase D (PLD) activity] by three- to sixfold. The effect of CCh on PEt formation also was dose dependent (EC50 = 50 microM). Both effects of CCh were antagonized by atropine, indicating that they were mediated by mAChR. Incubation of LA-N-2 cells with the phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1 microM; 10 min) increased [3H]PEt levels by up to 10-fold. This effect was inhibited by the protein kinase C (PKC) inhibitor staurosporine (1 microM) or by pretreatment for 24 h with 0.1 microM PMA, by 74% and 65%, respectively. In contrast, the effect of CCh on PEt accumulation was attenuated by only 28% in the presence of staurosporine (1 microM). In summary, these results suggest that, in LA-N-2 neuroblastoma cells, mAChR are coupled both to phosphoinositide-specific PLC and to PLD. PKC is capable of stimulating PLD activity in these cells; however, it is not required for stimulation of the enzyme by mAChR activation.
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PMID:Stimulation of phospholipase D activity in human neuroblastoma (LA-N-2) cells by activation of muscarinic acetylcholine receptors or by phorbol esters: relationship to phosphoinositide turnover. 200 44

The effects of toxin II (AaH II) isolated from the scorpion Androctonus australis Hector on sodium current in neuroblastoma X glioma NG 108-15 hybrid cells were analysed under patch clamp conditions in the whole cell configuration. AaH II (70 nM) induced a maintained sodium current, as well as increasing both fast and slow inactivation time constants and the amplitude of the peak current. This latter effect occurred via a shift of the activation-voltage curve towards negative voltage values by about 9 mV. Oleic acid (5 microM), which had no effect on INa under control conditions, decreased the AaH II-induced maintained current. It also reversed, or prevented the increase of the peak current induced by AaH II. However, it neither prevented nor modified the AaH II-induced increase in inactivation time constants. The binding of the toxin to its specific site and the number of binding sites for AaH II were not significantly modified by oleic acid. The oleic acid-induced effects could not be related to the activation of protein kinase C since PMA, a potent activator of this enzyme, did not produce oleic acid-like effects. From these results, it is concluded that AaH II has several independent effects on sodium channels, some of which could be modulated by the lipid environment of sodium channels in the membrane.
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PMID:Effects of toxin II from the scorpion Androctonus australis Hector on sodium current in neuroblastoma cells and their modulation by oleic acid. 253 22

delta 9-tetrahydrocannabinol, the major psychoactive cannabinoid of marijuana modulates immune cells in vivo and in vitro. It is possible that the drug exerts it's effect either by inserting into and disrupting the cell membrane (nonreceptor mechanism) or by binding to a cannabinoid receptor moiety and thus altering cell function through some form of signal transduction. In the present study, we confirm and extend the findings that mouse and human immune cells express specific cannabinoid binding sites and cannabinoid receptor mRNA. Reverse transcription-polymerase chain reaction analysis showed the presence of receptor mRNA not only in the neuroblastoma cell line (N18TG-2), but also in mouse splenocytes and in cell lines such as NKB61A2 (a mouse natural killer-like), CTLL2 (a mouse IL2-dependent T cell), THP-1 (a human monocytic cell) and Raji (a human B cell) but not in Jurkat (a human T cell). Furthermore, the receptor mRNA was expressed in purified populations of resting splenic T and B lymphocytes but not in resting populations of enriched splenic macrophages. Finally, LPS-stimulated Raji and PMA-stimulated THP-1 human cell lines showed increased levels of the cannabinoid receptor mRNA. These results suggest cannabinoid receptors have biological relevance in lymphoid cells because: receptor mRNA is detected in some resting immune cells but not others and the mRNA increases during cell activation. The major psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC), has been shown to modulate human and mouse immune responses both in vitro and in vivo (1,2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of cannabinoid receptor mRNA in murine and human leukocytes. 754 49

The effect of hypericin, an antiviral agent and inhibitor of protein kinase C (PKC), on cell proliferation and programmed death was investigated in the human neuroblastoma cell line SK-N-SH. Hypericin induced significant growth inhibition in a dose-dependent manner demonstrated by a microculture tetrazolium (MTT) assay. DNA isolated from cells treated with hypericin at concentrations over 1 microM exhibited a 'ladder' pattern of oligonucleosome-sized fragments characteristic of apoptosis. Similarly, treatment of the cells with the PKC inhibitors staurosporine, tamoxifen or phorbol ester PMA for 72 h also resulted in apoptosis, suggesting that hypericin may be triggering an apoptotic signal in neuroblastoma cells, which at least in part may be mediated by the inhibition of PKC.
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PMID:Growth inhibition and apoptosis in human neuroblastoma SK-N-SH cells induced by hypericin, a potent inhibitor of protein kinase C. 755 5

Protein kinase C (PKC) consists of a family of closely related subtypes which differ in their localization and activation properties. Our previous studies have suggested a role for PKC in the regulation of noradrenaline (NA) release from the human neuroblastoma SH-SY5Y. Here we have used two approaches to characterize the PKC subtypes present in SH-SY5Y cells. Firstly, the PCR was used to show that SH-SY5Y cells contain mRNA encoding PKC subtypes alpha, beta, gamma, delta, epsilon and zeta. Secondly, immunoblotting showed that SH-SY5Y cells express PKC subtypes alpha, epsilon and zeta at the protein level. Prolonged (48 h) exposure of cells to the phorbol ester phorbol 12-myristate 13-acetate (PMA; 100 nM) resulted in a marked decrease in the amounts of PKC-alpha and PKC-epsilon, with no change in levels of PKC-zeta. Prolonged PMA treatment had no significant effect on K(+)-evoked NA release from SH-SY5Y cells, whereas carbachol-evoked release was increased 2.2-fold. However, prolonged exposure to PMA completely inhibited the ability of acute (12 min) PMA treatment to enhance both K(+)- and carbachol-evoked NA release. The specific PKC inhibitor RO 31-7459 (10 microM) was found to inhibit K(+)- and carbachol-evoked release by 27% and 68% respectively. RO 31-7549 also completely inhibited the ability of acute PMA treatment to enhance release. These data suggest that PKC-alpha and/or PKC-epsilon play an essential role in the regulation of PMA-enhanced K(+)- and carbachol-evoked NA release in SH-SY5Y cells.
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PMID:A role for protein kinase C subtypes alpha and epsilon in phorbol-ester-enhanced K(+)- and carbachol-evoked noradrenaline release from the human neuroblastoma SH-SY5Y. 829 48

Interferon-gamma (IFN-gamma) is a potent growth-inhibitory cytokine also endowed with differentiating activity on neural cells. Binding of IFN-gamma to its high-affinity receptor induces a rapid and transient activation of phospholipase A2 (PLA2). The mechanism coupling the IFN-gamma receptor (IFN-gamma-R) to PLA2 activation is not clearly defined, and no information is available on this mechanism in neuroblast cells. We have tested the hypothesis that GTP-binding proteins (G-proteins) may couple the IFN-gamma-R to PLA2 in the human neuroblastoma (NB) cell line LAN-5. Incubation of NB cells with IFN-gamma resulted in a rapid increase in [3H]arachidonic acid (AA) release, and this effect was blocked by pretreatment with anti-IFN-gamma antibodies. IFN-gamma-stimulated AA release was still observed in permeabilized cells that were blocked by pretreatment with anti-IFN-gamma-R antibodies. Exposure of permeabilized LAN-5 cells to guanosine 5'-[gamma-thio]triphosphate (GTP[S]), a non-hydrolysable GTP analogue, induced a dose-dependent release of [3H]AA. A non-specific nucleotide effect was excluded, since similar stimulatory effects on AA mobilization were not observed by GTP, ATP, CTP, ADP and GDP. IFN-gamma-stimulated AA release was completely blocked by the guanine nucleotide analogue that inhibits G-protein function, guanosine 5'-[beta-thio]diphosphate (GDP[S]). A role for G-proteins in IFN-gamma-R coupling to PLA2 was further supported by the inhibition of IFN-gamma-induced [3H]AA release by treatment of permeabilized cells with pertussis toxin and with the antiserum against the common alpha-subunits of G-proteins. To determine a possible contribution to AA mobilization by the phospholipase C and diacyglycerol lipase pathway or by protein kinase C activation, the effects of neomycin, a phospholipase C inhibitor, and PMA (phorbol 12-myristate 13-acetate), a direct activator of protein kinase C, were investigated. Neither neomycin nor PMA affected either basal or IFN-gamma-stimulated AA release. Ca2+ concentration, which has been shown to regulate the activity of some PLA2s, does not appear to play an important role in the regulation of the IFN-gamma-stimulated PLA2 activity, since incubating permeabilized cells in different concentrations of Ca2+ induced AA release without affecting the IFN-gamma response. Altogether, these findings suggest the existence of IFN-gamma-R, which couples a Ca(2+)-independent PLA2 activation via pertussis-toxin-sensitive G-proteins.
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PMID:Interferon-gamma-stimulated and GTP-binding-proteins-mediated phospholipase A2 activation in human neuroblasts. 839 12

Treatment of 8-Br-cAMP promotes neurite outgrowth and neuronal differentiation in N1E115 mouse neuroblastoma cells. Prior or simultaneous treatment of PMA blocks 8-Br-cAMP-mediated neurite outgrowth. Phosphorylation of cellular proteins during these treatments was examined in a permeabilized cell system. While PMA promotes phosphorylation of the heat-stable protein kinase C substrates MARCKS and neuromodulin, 8-Br-cAMP hastens the dephosphorylation of a protein of M(r)95k (p95). Extensively purified, N-terminal sequenced, and judged from its phosphorylation properties, p95 was identified as the eukaryotic elongation factor-2 (eEF-2), whose dephosphorylation has been reported to be related to an increase in protein synthesis. It is likely 8-Br-cAMP stimulates dephosphorylation of eEf-2, promotes protein synthesis that eventually leads to neuronal differentiation in N1E115 cells.
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PMID:Identification of a rapidly dephosphorylating 95-kDa protein as elongation factor 2 during 8-Br-cAMP treatment of N1E115 neuroblastoma cells. 852

Single 5-HT3 receptor-gated ion channels were recorded in cell-attached and excised membrane patches of mouse N1E-115 neuroblastoma cells. In cell-attached patches 5-HT3 receptor-gated ion channels show distinct conductance levels of 27, 18, 11 and 6 pS. Patch excision, buffering of intracellular Ca2+ by BAPTA and inhibition of protein kinase activity by staurosporine increase the probability of occurrence of the 6 pS level and decrease that of the 27 pS level. Conversely, patch cramming and stimulation of protein kinase activity by the phorbol ester PMA enhance the probability of occurrence of the 27 pS level and decrease that of low conductance levels. We conclude that phosphorylation controls the conductance of 5-HT3 receptor ligand-gated ion channels. Control of channel conductance may prove an additional mechanism in the modulation of synaptic efficacy.
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PMID:Phosphorylation controls conductance of 5-HT3 receptor ligand-gated ion channels. 858 95


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