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)

Nitric-oxide synthase (NOS) is responsible for the synthesis of nitric oxide which serves as a neural messenger in the central nervous system. NOS activity was markedly inhibited in brains of mice and hamsters and neuroblastoma cells infected with scrapie (ScN2a). The decrease in activity was in accordance with decreased NADPH-diaphorase-positive cells and decreased staining of NOS-positive cells demonstrated by specific anti-NOS antibodies. However, the specific nNOS mRNA in ScN2a was elevated when compared with normal neuroblastoma cells (N2a). Immunoblotting of fractions from these cell lines with an anti-nNOS monoclonal antibody revealed a band of nNOS from N2a and two bands with a lower molecular weight in ScN2a cells. Furthermore, NOS in ScN2a cells was insoluble in nondenaturing detergents. This insolubility is one of the landmark properties of PrPSc. It is, therefore, possible that nNOS in scrapie-infected cells and brains is aberrantly folded, resulting in an insoluble and inactive enzyme.
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PMID:Effect of scrapie infection on the activity of neuronal nitric-oxide synthase in brain and neuroblastoma cells. 866 7

In order to clarify the role of cytosolic Ca2+ buffering, a property that in living cells is sustained primarily by high affinity binding proteins, in NMDA receptor-sustained neuron excitotoxicity, cultures of the neuroblastoma line CHP 100 (which is known to express the receptor) were loaded with the chelator BAPTA by incubation with various concentrations (0.03-1 microM) of its acetoxymethylester derivative. The effectiveness of the loading in terms of cytosolic buffering was confirmed by fura-2 measurement experiments in which the [Ca2+]i transients induced by cell exposure to ATP were blunted in the initial peak (up to -75%) and also in the following plateau. When the BAPTA-loaded neuroblastoma cells were exposed to NMDA (1 mM), excitotoxicity was reduced dose-dependently up to almost 70%, while the generation of cGMP was inhibited up to completion. The latter result suggested the possible involvement of nitric oxide in the NMDA-induced excitoxicity, a mechanism confirmed by the dose-dependent inhibitory effect induced by the nitric oxide synthase blocker, L-N-(1-iminoethyl)-ornithine, which protected the cells completely when administered at 300 microM. Flow cytometry analysis of DNA revealed that the mechanism of excitotoxicity in CHP100 cells does not involve apoptosis. We conclude that cytosolic Ca2+ buffering, a property known to vary considerably among neuronal cells and to change in some neurons also during ageing, has a general protective effect. Such a protection appears to take place via the blunting of the glutamate-induced [Ca2+]i responses mediated by the NMDA receptor, with prevention of the ensuing overactivation of nitric oxide synthase and of the irreversible derangement of the ionic homeostasis of the cell.
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PMID:Cytosolic Ca2+ buffering, a cell property that in some neurons markedly decreases during aging, has a protective effect against NMDA/nitric oxide-induced excitotoxicity. 876 26

Inward currents activated by 8-bromc-cGMP and by muscarinic agonist were compared in N1E-115 mouse neuroblastoma cells using perforated-patch voltage clamp and Fura-2 imaging. The cGMP analog activates a voltage-independent inward current that is carried at least in part by Ca2+ because it persists in Na(+)-free saline when Ca2+ is present and is blocked by external Mn2+ and Ba2+. The current is similar to the inward current that develops during stimulation of M1 muscarinic receptors, and the currents activated by agonist and by 8-bromo-cGMP are not additive, indicating that the same pathway is involved. Inhibition of cGMP production with NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide (NO)-synthase, prevents activation of Ca2+ current by agonist without affecting the content of intracellular Ca2+ stores or the ability of agonist to mobilize Ca2+. The inhibition is overcome by 8-bromo-cGMP. LY83583, a competitive inhibitor of guanylyl cyclase, reversibly blocks activation of Ca2+ current by agonist, again without affecting the content of Ca2+ stores or Ca2+ release. Rp-8-pCPT-cGMPS, an inhibitory analog of cGMP, also reduces the Ca2+ current and reduces Ca2+ influx during muscarinic activation. It is concluded that cGMP is the necessary and sufficient intermediate in the pathway linking muscarinic receptor occupancy to the activation of voltage-independent Ca2+ current. The pathway involves positive feedback. Calcium entering via voltage-independent channels preferentially stimulates NO-synthase, which leads to enhanced cGMP production and greater Ca2+ influx. Positive feedback may explain the rapid increase in cGMP that occurs during muscarinic receptor activation.
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PMID:The nitric oxide/cGMP pathway couples muscarinic receptors to the activation of Ca2+ influx. 877 38

We developed a simplified protocol for sensitive quantitation of mRNA using polymerase chain reaction (PCR) amplification of cDNA made by reverse transcriptase (RT), as resolved with capillary electrophoresis (CE) and detected with laser-induced fluorescence (LIF). The conditions required for adequate accuracy of the simplified version of the RT/PCR quantitation, in which a single concentration of external standard and amplification to within or near the plateau phase are used, were established for assay of mRNAs expressed at high, moderate, and low abundance. The mRNAs for the cytosolic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH) and the growth-associated protein GAP-43 in cultured SN49 neuroblastoma cells were used as target genes for high and moderate levels of expression, respectively. Using cultured mouse microglial cells (BV-2), we demonstrated the utility of this RT/PCR/CE/LIF protocol to quantitate a low-abundance mRNA, encoding a form of nitric oxide synthase (i-NOS) induced by treatment with endotoxin. The appearance of i-NOS mRNA after endotoxin treatment of BV-2 cells was confirmed by Northern blot analysis and in situ hybridization histochemistry, and functional enzyme activity was followed by release of nitric oxide (as nitrite) into the medium. The many advantages of the 'single-point' RT/PCR/CE/LIF protocol for quantitating mRNAs of interest include: simplified protocol, elimination of the use of radiotracers, high sensitivity and precision, and semi-automation of the quantitation phase of analysis.
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PMID:Simplified RT/PCR quantitation of gene transcripts in cultured neuroblastoma (SN49) and microglial (BV-2) cells using capillary electrophoresis and laser-induced fluorescence. 881 12

We examined the release of tetrahydrobiopterin ((6R)-L-erythro-dihydroxypropyl-2-amino-4-hydroxy-5,6,7, 8-tetrahydropteridine; BH4) and nitric oxide induced by lipopolysaccharide from mouse neuroblastoma N1E-115 cells by measuring BH4 and nitric oxide derivatives, nitrites and nitrates, harbored in the conditioned media. The stimulation of the cells by 1 microgram/ml of lipopolysaccharide for 24 h induced 2-fold increase in the release of BH4 from the cells, but did not induce the nitric oxide release from the cells. Although such increase in BH4 release from the cells was blocked by the inhibitors of nuclear factor-kappa B or protein tyrosine kinases, the release of nitric oxide was not affected by such inhibitors. Our results may suggest that the inductions of BH4 and nitric oxide in this neuroblastoma cell line are processed in different ways and that this cell line is also different from the immune cells in the central nervous system such as microglia in this respect.
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PMID:Dissociated release of tetrahydrobiopterin and nitric oxide by lipopolysaccharide from mouse neuroblastoma cells. 883 57

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

The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate. In vivo, the mortality rate increased as the NOS activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro-L-arginine methyl ester. Moreover, when an organic donor, S-nitro-N-acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as well as in persistently JEV-infected C2-2 cells. These data reaffirm that NO has an effective and broad-spectrum antimicrobial activity against diversified intracellular pathogens. Interestingly, the antiviral effect of NO was not enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure which has been shown to greatly increase the antiviral effect of NO in infection by vesicular stomatitis virus. From biochemical analysis of the impact of NO on JEV replication in cell culture, NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells. The results herein thus suggest that NO may play a crucial role in the innate immunity of the host to restrict the initial stage of JEV infection in the central nervous system.
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PMID:Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication. 918 90

Neuroblastoma cell lines (SK-N-SH and SK-N-MC) were induced to differentiate, as detected by the expression of neurofilament proteins of 68 and 200 kDa, and to express adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule) after stimulation with tumour necrosis factor-alpha (TNF-alpha). This induction was accompanied by the arrest of cell growth. The induction of neuroblastoma adhesion by TNF-alpha could be inhibited by the nitric oxide synthase inhibitors, L-N-monomethyl arginine (L-NMMA) and L-N6-(1-imidoethyl)-lysine (highly specific for the inducible enzyme), but not by the inactive enantiomer D-NMMA. These results indicate that TNF-alpha induces the adhesion of neuroblastoma cells via nitric oxide. This was confirmed by the finding that the adhesion/differentiation of SK-N-SH and SK-N-MC cells can be directly induced by the addition of nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetyl-penicillamine, into the culture medium. The isoform of the nitric oxide synthase induced in human neuroblastoma cells by TNF-alpha treatment was identified enzymatically as isoform II by Western blotting and by the polymerase chain reaction. Thus TNF-alpha induces the in vitro adhesion/differentiation of human neuroblastoma cells through nitric oxide synthesized by a calcium-independent inducible form of nitric oxide synthase, clearly indicating that isoform II of nitric oxide synthase can be expressed in human neuronal cell types.
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PMID:Induction of adhesion/differentiation of human neuroblastoma cells by tumour necrosis factor-alpha requires the expression of an inducible nitric oxide synthase. 921 2

We investigated the coupling of the M2 muscarinic acetylcholine receptors expressed in Chinese hamster ovary cells to activation of neuronal nitric oxide (NO) synthase. Stimulation of guanylate cyclase activity in detector neuroblastoma cells was used as an indirect measure of the generation of NO in Chinese hamster ovary cells. The muscarinic agonist carbachol induced marked time- and concentration-dependent enhancement of the activity of NO synthase. Activation of neuronal NO synthase by M2 muscarinic receptors was associated with a small increase in the concentration of intracellular Ca2+. These data suggest the presence of alternate mechanisms of activation of neuronal NO synthase which might be operative in the absence of large changes in the concentration of cellular Ca2+. These findings help to understand the mechanisms of activation of NO synthase.
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PMID:Activation of neuronal nitric oxide synthase by M2 muscarinic receptors associated with a small increase in intracellular calcium. 930 96

The N-methyl-D-aspartate (NMDA) receptor has been reported to be important in synaptic plasticity, neuronal development, normal brain function and neurologic disease. We have recently shown that PC12W cells, a subclone of rat pheochromocytoma PC12 cell line, release nitric oxide (NO), as measured by in vitro spin-trapping combined with electron paramagnetic resonance (EPR) spectroscopy, when challenged with NMDA [Norby, S.W., Weyhenmeyer, J.A. and Clarkson, R.B., Stimulation and inhibition of NO production in macrophages and neuronal cells as observed by spin trapping, Free Rad. Biol. Med., 22 (1997) 1-9]. In the present study, we provide immunochemical evidence for the expression of both the NMDAR1 and NMDAR2A/B receptor subunits in PC12W cells, that express only the angiotensin type-2 (AT2) receptor subtype, and in NG108-15 (NG108) cells, a murine neuroblastoma x glioma hybrid that expresses both the angiotensin type-1 (AT1) and AT2 receptor subtypes. We also show that treatment of PC12W cells with angiotensin (Ang II) decreases NMDA-induced NO release by 28.0 +/- 4.2%, and that this response can be attenuated by pre-treating the cells with the isoform-specific AT2 antagonist, PD 123319. Interestingly, there was no effect on cGMP accumulation in PC12W cells treated with NMDA. Similar experiments were carried out using NG108 cells since the binding properties and functional characteristics of their NMDA receptors have been previously described [Ohkuma, S., Katsura, M., Chen, D., Chen, S. and Kuriyama, K., Presence of N-methyl-D-aspartate (NMDA) receptors in neuroblastoma x glioma hybrid NG 108-15 cells-analysis using 45Ca2+ influx and [3H]MK-801 binding as functional measures, Mol. Brain Res. 22 (1994) 166-172]. Our results show that NG108 cells significantly increase cGMP levels when challenged with NMDA (21.2 +/- 5.0% over control levels), and that this response can be attenuated by the addition of angiotensin (57.1 +/- 6.2% of stimulated levels). The effect of angiotensin on NMDA-mediated changes in cGMP levels was blocked by the AT2 antagonist, PD 123319, but was not significantly changed by the addition of the AT1 antagonist, losartan. Further, Ang II action on NMDA signalling in NG108 cells was completely inhibited by the addition of both the AT1 and AT2 antagonists. Taken together, these results suggest that AngII inhibits NMDA-mediated NO and cGMP production through a mechanism involving the AT2 receptor subtype.
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PMID:Angiotensin II type-2 (AT2) receptor-mediated inhibition of NMDA receptor signalling in neuronal cells. 933 16


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