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)

Recently, it has been shown that rotenone, a specific inhibitor of mitochondrial complex I, is a useful tool in animal models of Parkinson's disease, but the mechanism of rotenone-induced neuronal death is not fully understood. In human neuroblastoma SH-SY5Y cells, rotenone induced the degradation of procaspases-12, -9 and -3, followed by cleavage of poly (adenosine diphosphate-ribose) polymerase, DNA fragmentation and cell death. Pretreatment with phorbol-12-myristate-13-acetate inhibited the rotenone-induced decrease in procaspases-9 and -3, but not that in procaspase-12. In contrast, benzyloxycarbonyl-Val-Ala-Asp(OCH(3))-CH(2)F inhibited the decrease in procaspase-12, but not those in procaspases-9 and -3 in this study. These results suggest that rotenone may induce activation of both mitochondria- and endoplasmic reticulum-dependent caspases in human SH-SY5Y cells.
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PMID:Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. 1240 52

A ligand-independent activator of heterotrimeric brain G-protein was partially purified from detergent-solubilized extracts of the neuroblastoma-glioma cell hybrid NG108-15. The G-protein activator (NG108-15 G-protein activator (NG-GPA)) increased [(35)S]guanosine 5'-O-(thiotriphosphate) ([(35)S]GTPgammaS) to purified brain G-protein in a magnesium-dependent manner and promoted GDP dissociation from Galpha(o). The NG-GPA also increased GTPgammaS binding to purified, recombinant Galpha(i2), Galpha(i3), and Galpha(o), but minimally altered nucleotide binding to purified transducin. The NG-GPA increased GTPgammaS binding to membrane-bound G-proteins and inhibited basal, forskolin- and hormone-stimulated adenylyl cyclase activity in DDT(1)-MF-2 cell membranes. In contrast to G-protein coupled receptor-mediated activation of heterotrimeric G-proteins in DDT(1)-MF-2 cell membrane preparations, the action of the NG-GPA was not altered by treatment of the cells with pertussis toxin. ADP-ribosylation of purified brain G-protein also failed to alter the increase in GTPgammaS binding elicited by the NG-GPA. Thus, the NG-GPA acts in a manner distinct from that of a G-protein coupled receptor and other recently described receptor-independent activators of G-protein signaling. These data indicate the presence of unexpected regulatory domains on G(i)/G(o) proteins and suggest the existence of pertussis toxin-insensitive modes of signal input to G(i)/G(o) signaling systems.
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PMID:Pertussis toxin-insensitive activation of the heterotrimeric G-proteins Gi/Go by the NG108-15 G-protein activator. 1242 23

Extracellular nucleotides exert a variety of biological actions through several kinds of P2 receptors in many tissues and cell types. We found that treatment with nucleotides increases intracellular Ca2+ concentration ([Ca2+]i) in SK-N-BE(2)C human neuroblastoma cells with a following order of potency: UDP > UTP > ADP >> ATP. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that specific mRNAs coding for human P2Y1, P2Y4, and P2Y6 receptors were expressed in the cells, but Northern blot analysis revealed that P2Y6 receptors were the predominant type. Activation of protein kinase C-alpha by treatment with 1 micro m phorbol 12-myristate 13-acetate dramatically inhibited both the UDP-induced [Ca2+]i rise and inositol 1,4,5-trisphosphate (IP3) generation, whereas incubation with pertussis toxin had little effect on the responses. The UDP-induced [Ca2+]i rise and IP3 production were maintained up to 30 min after stimulation, while bradykinin-induced responses rapidly decreased to the basal level within 5 min of stimulation. Pretreatment of cells with the maximal effective concentration of UDP reduced the subsequent carbachol- or bradykinin-induced [Ca2+]i rise without inhibition of IP3 generation. Neuronal differentiation of the cells by treatment with retinoic acid for 7 days did not change the expression level of P2Y6 receptors. Taken together, the data indicate that P2Y6 receptors highly responsive to diphosphonucleotide UDP are endogenously expressed in the human neuroblastoma SK-N-BE(2)C cells and that they are involved in the modulation of other phospholipase C-coupled receptor-mediated Ca2+ mobilization by depleting the IP3-sensitive Ca2+ stores.
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PMID:Attenuation of signal flow from P2Y6 receptor by protein kinase C-alpha in SK-N-BE(2)C human neuroblastoma cells. 1271 36

Transmissible spongiform encephalopathies (TSEs), also called prion diseases, are characterized by formation of the disease-associated isoform of prion protein (PrP(Sc)), which arises from a normal isoform termed PrP(c) by a post-translational conversion process occurring in an autocatalytic fashion. Oxidative stress has been proposed as a pathogenetic mechanism in TSEs and increased lipid peroxidation has recently been described in prion-infected cell cultures, suggesting an intrinsic link between the presence of prions and oxidative stress. We investigated if poly(ADP-ribose) formation can be detected in cultured cells upon prion infection, as this NAD+-consuming and DNA strand break-activated nuclear enzymatic reaction has the potential to cause rapid and lethal NAD+ depletion in cells under severe oxidative stress. Poly(ADP-ribose) production was analysed by immunofluorescence in freshly scrapie-infected Neuro2a-D11 mouse neuroblastoma cells, which had been confirmed by immunocytochemistry to produce PrP(Sc), and in uninfected controls. No spontaneous poly(ADP-ribose) specific signals were observed in infected or in uninfected cells, while both cell types readily reacted to H2O2 treatment with poly(ADP-ribose) synthesis in a dose-dependent manner, with no obvious difference in staining intensity at any dose tested. In summary, our data reveal that replication of scrapie agent in neuroblastoma cells can proceed without detectable stimulation of the cellular poly(ADP-ribosyl)ation system.
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PMID:In-situ analysis of cellular poly(ADP-ribose) production in scrapie-infected mouse neuroblastoma cells. 1276 68

1. The metabolism of extracellular nucleotides in NG108-15 cells, a neuroblastoma x glioma hybrid cell line, was studied by means of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC). 2. In NG108-15 cells ATP, ADP, AMP, UTP, UDP, and UMP were hydrolyzed to the nucleosides adenosine and uridine indicating the presence of ecto-nucleotidases and ectophosphatases. The hydrolysis of the purine nucleotides ATP and ADP was significantly faster than the hydrolysis of the pyrimidine nucleotides UTP and UDP. 3. ATP and UTP breakdown appeared to be mainly due to an ecto-nucleotide-diphosphohydrolase. ADP, but not UDP, was initially also phosphorylated to some extent to the corresponding triphosphate, indicating the presence of an adenylate kinase on NG108-15 cells. The alkaline phosphatase (ALP) inhibitor levamisole did not only inhibit the hydrolysis of AMP to adenosine and of UMP to uridine, but also the degradation of ADP and to a larger extent that of UDP. ATP and UTP degradation was only slightly inhibited by levamisole. 4. These results underscore the important role of ecto-alkaline phosphatase in the metabolism of adenine as well as uracil nucleotides in NG108-15 cells Dipyridamole, a potent inhibitor of nucleotide breakdown in superior cervical ganglion cells, had no effect on nucleotide degradation in NG108-15 cells. 5. Dipyridamole, which is a therapeutically used nucleoside reuptake inhibitor in humans, reduced the extracellular adenosine accumulation possibly by allosteric enhancement of adenosine reuptake into the cells.
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PMID:Extracellular metabolism of nucleotides in neuroblastoma x glioma NG108-15 cells determined by capillary electrophoresis. 1282 32

Experiments were carried out to assess whether a magnetic field of 50 Hz and 1 mT can influence apoptosis and proliferation in the human neuroblastoma cell line LAN-5. TUNEL assays and poly-ADP ribose polymerase (PARP) expression analysis were performed to test apoptosis induction, and the WST-1 assay was used to calculate the proliferation index in a long term exposure. No alterations were found in cellular ability to undergo programmed cell death, but a small increase in the proliferation index was evidenced after 7 days of continuous exposure. Also, a slight and transient increase of B-myb oncogene expression was detected after 5 days of exposure. Combined exposures of cells to EMF and to chemical agents which interfere with proliferation, such as the differentiative agent retinoic acid and the apoptotic inducer camptothecin, showed an antagonistic effect of magnetic fields against the differentiation of the LAN-5 cells and a protective effect towards apoptosis.
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PMID:Effects of 50 Hz electromagnetic field exposure on apoptosis and differentiation in a neuroblastoma cell line. 1295 56

Adenylate kinases (AK, EC 2.7.4.3) have been considered important enzymes for energy homeostasis and metabolic signaling. To gain a better understanding of their cell-specific significance we studied the structural and functional aspects of products of one adenylate kinase gene, AK1, in mouse tissues. By combined computer database comparison and Northern analysis of mRNAs, we identified transcripts of 0.7 and 2.0 kilobases with different 5' and 3' non-coding regions which result from alternative use of promoters and polyadenylation sites. These mRNAs specify two distinct proteins, AK1 and a membrane-bound AK1 isoform (AK1beta), which differ in their N-terminal end and are co-expressed in several tissues with high-energy demand, including the brain. Immunohistochemical analysis of brain tissue and primary neurons and astrocytes in culture demonstrated that AK1 isoforms are expressed predominantly in neurons. AK1beta, when tested in transfected COS-1 and N2a neuroblastoma cells, located at the cellular membrane and was able to catalyze phosphorylation of ADP in vitro. In addition, AK1beta mediated AMP-induced activation of recombinant ATP-sensitive potassium channels in the presence of ATP. Thus, two structurally distinct AK1 isoforms co-exist in the mouse brain within distinct cellular locations. These enzymes may function in promoting energy homeostasis in the compartmentalized cytosol and in translating cellular energetic signals to membrane metabolic sensors.
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PMID:Two structurally distinct and spatially compartmentalized adenylate kinases are expressed from the AK1 gene in mouse brain. 1497 70

We synthesized analogs modified in the ribose unit (ribose linked to N1 of adenine) of cyclic ADP-ribose (cADPR), a Ca2+-mobilizing second messenger. The biological activities of these analogs were determined in NG108-15 neuroblastoma x glioma hybrid cells that were pre-loaded with fura-2 acetoxymethylester and subjected to whole-cell patch-clamp. Application of the hydrolysis-resistant cyclic ADP-carbocyclic-ribose (cADPcR) through patch pipettes potentiated elevation of the cytoplasmic free Ca2+ concentration ([Ca2+]i) at the depolarized membrane potential. The increase in [Ca2+]i evoked upon sustained membrane depolarization was significantly larger in cADPcR-infused cells than in non-infused cells and its degree was equivalent to or significantly greater than that induced by cADPR or beta-NAD+. 8-Chloro-cADPcR and two inosine congeners (cyclic IDP-carbocyclic-ribose and 8-bromo-cyclic IDP-carbocyclic-ribose) did not induce effects similar to those of cADPcR or cADPR. Instead, 8-chloro-cADPcR together with cADPR or cADPcR caused inhibition of the depolarization-induced [Ca2+]i increase as compared with either cADPR or cADPcR alone. These results demonstrated that our cADPR analogs have agonistic or antagonistic effects on the depolarization-induced [Ca2+]i increase and suggested the presence of functional reciprocal coupling between ryanodine receptors and voltage-activated Ca2+ channels via cADPR in mammalian neuronal cells.
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PMID:Amplification of depolarization-induced and ryanodine-sensitive cytosolic Ca2+ elevation by synthetic carbocyclic analogs of cyclic ADP-ribose and their antagonistic effects in NG108-15 neuronal cells. 1599 83

The anti-Parkinson drug, rasagiline (N-propargyl-(1R)-aminoindan) promotes neuronal survival, via neuroprotective activity related to its propargyl moiety (propargylamine). We have investigated the neurorescue effects of propargylamine, in a progressive neuronal death model, induced by long-term serum deprivation in human SH-SY5Y neuroblastoma cells. Propargylamine (0.1-10 microM) dose-dependently reduced the levels of the early apoptosis-associated phosphorylated protein, H2A-X (ser 139), as well as decreased the cleavage of caspase-3 and its substrate poly-ADP ribose polymerase (PARP). In addition, the compound markedly reversed the apoptotic effects induced by long-term serum withdrawal, including down-regulation of the antiapoptotic protein, Bcl-2, as well as up-regulation of the proapoptotic proteins, Bax, Bad, and Bim. Real-time RT-PCR demonstrated that propargylamine elevated gene expression levels of Bcl-2, and the neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) and reduced Bax gene expression. Serum deprivation increased mRNA and protein levels of holo-amyloid precursor protein (APP), which was markedly decreased by propargylamine. This was accompanied by inducing the release of the nonamyloidogenic alpha-secretase form of soluble APP (sAPPalpha) into the medium. Similar effects on cell survival and APP regulation/processing were demonstrated for rasagiline. These results indicate that both rasagiline and propargylamine possess neurorescue activity, associated with regulation of Bcl-2 family proteins, neurotrophic factors, and APP metabolism.
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PMID:Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine. 1614 27

Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often the effector molecules of pathogens responsible for virulence. Many virulence proteins are detected indirectly by plant NBS-LRR proteins from modifications the virulence proteins inflict on host target proteins. However, some NBS-LRR proteins directly bind pathogen proteins. Association with either a modified host protein or a pathogen protein leads to conformational changes in the amino-terminal and LRR domains of plant NBS-LRR proteins. Such conformational alterations are thought to promote the exchange of ADP for ATP by the NBS domain, which activates 'downstream' signaling, by an unknown mechanism, leading to pathogen resistance.
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PMID:Plant NBS-LRR proteins in pathogen sensing and host defense. 1711 Sep 40


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