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)

6-Hydroxydopamine (6-OHDA) is widely used to generate animal models of Parkinson's disease. However, little is known about the intracellular events leading to cell death of dopaminergic neurones. Here we correlate indices of energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to 6-OHDA. The toxin induces a time and dose-dependent decrease in cell survival with an IC50 value of 25 microM after 24 h. In contrast to the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+), 6-OHDA-induced reduction of cell viability is not associated with a decrease of intracellular ATP content, intracellular ATP/ADP ratio or NAD+ content. In addition, preventing or forcing glycolysis do not alter 6-OHDA toxicity. The antioxidant D-alpha-tocopherol can attenuate cell death induced by 6-OHDA. These results suggest that cell death induced by 6-OHDA is not due to an inhibition of mitochondrial energy supply, but probably involves production of free radicals.
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PMID:6-Hydroxydopamine toxicity towards human SH-SY5Y dopaminergic neuroblastoma cells: independent of mitochondrial energy metabolism. 1082 37

Kinetic interaction between thrombin receptor and G proteins was investigated in human epithelial neuroblastoma cell line, SH-EP. In these cells, both alpha-thrombin and SFLLRNP (one-letter amino-acid code) stimulated GTPase activity and enhanced cholera toxin-catalyzed ADP-ribosylation of G(i2) in a concentration-dependent manner. Basal GTPase activity was attenuated by pertussis toxin treatment by 35%, however, agonist stimulation was preserved significantly. These results together indicated that thrombin receptor simultaneously activates G(i2) and PTX-insensitive G protein(s).
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PMID:Thrombin stimulates pertussis toxin-sensitive and -insensitive GTPase activities and ADP-ribosylation of G(i) in human neuroblastoma SH-EP. 1089 75

ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that participate in both exocytic and endocytic vesicular transport pathways via mechanisms that are only partially understood. Although several ARF-like proteins (ARLs) are known, their biological functions remain unclear. To characterize its molecular properties, we cloned mouse and human ARL4 (mARL4 and hARL4) cDNA. The appearance of mouse ARL4 mRNA during embryonic development coincided temporally with the sequential formation of somites and the establishment of brain compartmentation. Using ARL4-specific antibody for immunofluorescence microscopy, we observed that endogenous mARL4 in cultured Sertoli and neuroblastoma cells was mainly concentrated in nuclei. When expressed in COS7 cells, ARL4-T34N mutant, predicted to exist with GDP bound, was concentrated in nucleoli. Yeast two-hybrid screening and in vitro protein-interaction assays showed that hARL4 interacted with importin-alpha through its C-terminal NLS region and that the interaction was not nucleotide-dependent. Like ARL2 and -3, recombinant hARL4 did not enhance cholera toxin-catalyzed auto-ADP-ribosylation. Its binding of guanosine 5'-O-(thiotriphosphate) was modified by phospholipid and detergent, and the N terminus of hARL4, like that of ARF, was myristoylated. Our findings suggest that ARL4, with its distinctive nuclear/nucleolar localization and pattern of developmental expression, may play a unique role(s) in neurogenesis and somitogenesis during embryonic development and in the early stages of spermatogenesis in adults.
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PMID:ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli. 1098 Jan 93

Studies on the cellular and molecular mechanism of neurotransmitter receptor-signaling and of neuronal and glial cell responses to stresses seem to be important to elucidate the action mechanism of centrally-acting drugs and to develop novel therapeutics against several diseases in the brain. The present review shows our findings with regard to the membrane receptor-signaling mechanism including serotonin, noradrenaline, glutamate receptors, ion channels, G-proteins, protein kinases and drug actions in Xenopus oocytes injected with rat brain mRNA, NG108-15 cells and brain membranes. Regarding the results of studies on the inter- and intra-cellular mechanism of neurons and glial cells against cerebral ischemia/hypoxia, we review the involvement of a transcription factor NF-kappa B in LPS-elicited inducible NO synthase (iNOS) expression in rat astroglial cells. Then we describe possible involvement of: 1) ADP-ribosylation/nitrosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 2) decrease in mitochondrial membrane potential, release of caspase-3 from mitochondria and degradation of the inhibitor of caspase-activated DNase by activated caspase in NO-induced neuronal apoptosis. We observed that hypoxia results in expression of a molecular chaperon such as protein disulfide isomerase (PDI) and HSP70 in astroglial cells. Our recent findings indicate that overexpression of PDI in the rat hippocampus (in vivo) and in neuroblastoma SK-N-MC cells (in vitro) significantly suppress the hypoxia-induced neuronal death. From physiological/pathophysiological and pharmacological aspects, we review the importance of studies on the cellular and molecular mechanism of membrane receptor-signaling and of stress-responses in the brain to identify functional roles of neuro-glial- as well as neuro-neuronal interaction in the brain.
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PMID:[Cellular and molecular pharmacological studies on membrane receptor-signaling and stress-responses in the brain]. 1176 4

Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme that is activated by DNA strand breaks and catalyzes the transfer of ADP-ribose groups from NAD to itself and other nuclear proteins. Although caspase-mediated PARP-1 cleavage occurs during almost all forms of apoptosis, the contribution of PARP-1 activation and cleavage to this cell death process remains unclear. Using immortalized fibroblasts from wild-type (PARP-1(+/+)) and PARP-1 knockout (PARP-1(-/-)) mice, and a mouse neuroblastoma cell line (N18), the role that poly(ADP-ribosyl)ation plays in Sindbis virus (SV)-induced apoptosis was examined. Robust PARP-1 activation occurred in SV-infected cells prior to morphologic changes associated with apoptotic cell death and PARP-1 activity ceased simultaneously with caspase-3 activation and PARP-1 proteolysis. PARP-1 activity was maximal before detectable DNA fragmentation, but was absent when DNA damage was most intense. SV and staurosporine-induced cell death was delayed in fibroblasts lacking PARP-1 activity, suggesting that PARP-1 activation contributes to apoptotic cell death induced by these stimuli. SV replication was not affected by lack of PARP-1 activity, but DNA fragmentation and caspase-3 activation were delayed and occurred at lower levels in PARP-1-deficient fibroblasts. Early virus-induced PARP-1 activation may represent a novel way by which cells signal to the nucleus to regulate protein function by poly(ADP-ribosyl)ation in response to virus infection.
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PMID:Rapid activation of poly(ADP-ribose) polymerase contributes to Sindbis virus and staurosporine-induced apoptotic cell death. 1185 9

The SK-N-MC cell line is frequently used as a model of neuronal differentiation induced by 5-bromodeoxyuridine (BrdU). In this study, the differentiation properties of this cell line were investigated under hydroxyl free radical generation, and compared to BrdU treatment. Hydroxyl free radicals were generated in the cultures by the Fenton reaction, i.e. by simultaneous addition of ADP-Fe2+ complex and H2O2. Microscopic morphological signs, as well as the acetylcholinesterase and ganglioside sialidase activities were considered as markers of neuronal differentiation of this cholinergic neuroblastoma cell line. Apart from the altered morphological appearance, the marker enzymes displayed significant increases after both types of intervention. We suggest that hydroxyl free radicals can induce in vitro cell differentiation. They apparently play a more complex role in cell physiology than simply causing oxidative damage.
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PMID:Hydroxyl free radicals induce cell differentiation in SK-N-MC neuroblastoma cells. 1198 68

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


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