Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of isoproterenol and N6,O2-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) induction of lactate dehydrogenase A subunit mRNA (mRNALDH) was investigated in the rat C6 glioma cell line. During the induction phase the concentration of nuclear mRNALDH sequences increased about 2.5-fold 4 h after the addition of isoproterenol or dibutyryl cAMP. Analysis of nuclear 32P-labeled mRNALDH sequences showed that isoproterenol or dibutyryl cAMP increased the basal rate of in vitro mRNALDH transcription about 3.6-fold within 4 h. The relative rates of in vivo mRNALDH synthesis were additionally measured by pulse-labeling of glioma cells for 15 min with [3H]uridine. The induction of mRNALDH in intact glioma cells by isoproterenol and dibutyryl cAMP was quantitatively comparable to that observed in isolated nuclei and the relative rate of [3H]uridine incorporation into mRNALDH was maximal 4 to 5 h after the initial induction stimulus. Increased synthesis of mRNALDH in vivo as well as in isolated nuclei occurred only at isoproterenol concentrations that caused elevated levels of glioma cell cAMP. Analysis of the kinetics of decay of [3H]uridine-labeled mRNALDH showed a linear rate of decay of non-induced mRNALDH with a t1/2 of 45 min. After isoproterenol stimulation mRNALDH decayed as two populations, one with a t1/2 of 50 min and the other one with a t1/2 of 2.5 h. These results indicate that both isoproterenol and dibutyrl cAMP regulate not only the rate of transcription of mRNALDH but that the stability of mRNALDH is increased during the induction phase.
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PMID:Cyclic AMP regulation of lactate dehydrogenase. Isoproterenol and N6,O2-dibutyryl cyclic amp increase the rate of transcription and change the stability of lactate dehydrogenase a subunit messenger RNA in rat C6 glioma cells. 630 Jan 27

Rat glioma X mouse neuroblastoma hybrid neurotumor cells (NG108-15), synchronized by amino acid deprivation, showed a cell-cycle-dependent peak of activity of a ganglioside N-acetylgalactosaminyl transferase 14-24 h following release from the cell cycle block (S/G2 phase). Maximal expression of two typical lysosomal hydrolases, N-acetyl-beta-hexosaminidase and beta-galactosidase, occurred between 18 and 21 h following release (S phase), declining to G1 phase levels during the peak of N-acetylgalactosamine (GalNAc) transferase activity. In addition, glycosyltransferase activity in G2 phase cells showed an increase in apparent Vmax (suggesting the presence of more enzyme/mg of cell protein) and apparent binding affinity for uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) (32 versus 14 microM) when compared to transferase activity in the G1 phase. However, the opioid peptide enkephalin [D-Ala2, D-Leu5], which inhibits ganglioside GalNAc transferase activity in unsynchronized NG108-15 cultures, was much more inhibitory in whole cells 8 h after release from the cell cycle block (G1 phase) than in cells 20 h after release (G2 phase), with 50% inhibition occurring at 2 X 10(-9) M and 2 X 10(-7) M, respectively. These results suggest that the GalNAc transferase activity is regulated in more than one way during the cell cycle, since both Vmax and Km changes are observed, and that the cyclic AMP-dependent mechanism by which opiates reduce transferase activity is receptor mediated and cell cycle dependent.
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PMID:Cell-cycle dependence of a ganglioside glycosyltransferase activity and its inhibition by enkephalin in a neurotumor cell line. 642

When C6-2B rat glioma cells were stimulated with calf serum in the presence of calcium, ornithine decarboxylase activity increased maximally in 6-8 h after an initial 2-3 h lag period wherein RNA synthesis occurred. The increase of ornithine decarboxylase activity in serum-stimulated C6-2B cells was prevented by the calcium chelator EGTA, but EGTA had no effect upon RNA synthesis as judged by [3H]uridine incorporation into RNA. In addition, the calcium requirement for increased ornithine decarboxylase activity was temporally distal to the lag period. EGTA appeared to inhibit the synthesis of ornithine decarboxylase, because the half-life values of ornithine decarboxylase activity were similar (37-47 min) in the presence of EGTA or protein synthesis inhibitors such as cycloheximide or emetine. Also, calcium readdition rapidly reversed EGTA inhibition of ornithine decarboxylase activity by a mechanism which could be blocked by cycloheximide.
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PMID:Dissociation of RNA synthesis from the calcium requirement for serum-increased ornithine decarboxylase activity in rat glioma cells. 643 60

ST1, a hydrocortisone-hypersensitive variant of the C6 rat glioma cell line, produced viral particles upon treatment with this glucocorticoid hormone. The virus was identified as type C RNA tumor virus by: a) morphology; b) 3H-uridine labelling; c) banding in sucrose density gradient; d) reverse transcriptase activity. Hydrocortisone uniquely shut off ST1 cells' transformed phenotype and turned on viral particles production.
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PMID:RNA tumor virus production accompanies the transformed phenotype change induced by hydrocortisone hormone in rat glioma cells. 662 5

We have identified and studied a posttranscriptional mechanism of lactate dehydrogenase A (LDH) subunit gene expression at the level of mRNA stability. Using the well differentiated rat C6 glioma cell line as a model system, the effects of activators of the protein kinase A and C pathways on the half-life of LDH A mRNA were measured by two independent methods: 1) by the RNA synthesis inhibitor-chase method using actinomycin D, and 2) by analysis of decay of LDH A [3H]mRNA in [3H]uridine-labeled cells. By each method, the half-life of relatively short-lived LDH A mRNA was increased 5- to 7-fold in 8- (4-chloro-phenylthio) cAMP or forskolin-treated and about 3-fold in 12-0-tetradecanoylphorbol-13- acetate (TPA) or dioctanoylglycerol-treated cells. Forskolin acted synergistically with TPA to prolong LDH A mRNA half-life from 55 min to more than 20 h. The relatively rapid basal decay rate of LDH A mRNA was also considerably slowed in the presence of the protein phosphatase inhibitor okadaic acid, suggesting a functional role for protein phosphorylation in the stabilization process. In glioma cells stably transformed with a protein kinase A catalytic subunit expression vector, overexpression of the catalytic subunit stabilized LDH mRNA to the degree seen in forskolin-treated cells. In cells transfected with a protein kinase A inhibitor-expression vector, cAMP-mediated stabilization of LDH A mRNA half-life was prevented. Furthermore, both staurosporin and 3- [1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol- 3-yl)- maleimide, inhibitors of protein kinase C, prevented the TPA-induced stabilization of LDH A mRNA. We conclude from the experimental data that the protein kinase A and C signal pathways play an active functional role in regulating LDH A mRNA stability and act cooperatively to achieve LDH A mRNA stability regulation.
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PMID:Lactate dehydrogenase A subunit messenger RNA stability is synergistically regulated via the protein kinase A and C signal transduction pathways. 747 96

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation. High concentrations of cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical glia. Cocaine exposure for four days decreased cell proliferation of cortical glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular syntheses was not due to cell death since cocaine-treated cells were not stained with Trypan Blue and did not release lactate dehydrogenase into culture supernatants. Furthermore, cocaine had no effect on glutamate uptake either in cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits macromolecular syntheses in glial cells. The inhibition of macromolecular syntheses in glial cells may be the mechanism involved in cocaine-induced fetal brain growth retardation.
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PMID:Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells. 750 70

In the search for cytokines whose antiproliferative action could be enhanced by combination with dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, the combination of tumor necrosis factor-alpha (TNF-alpha) with this agent was evaluated in various human tumor cell lines. Inhibition of the proliferation of human melanoma cell lines MM-1CB and HMV-1 by TNF-alpha (1-10(2) U/ml) was enhanced in culture dishes by combination treatment with dipyridamole (0.1-10 microM). The enhancement effect was also detected in other tumor cell lines: T98 (glioma), SCC-1CB (squamous cell carcinoma), HAC-2 (ovarian clear-cell carcinoma), HLE (hepatoma), HEC-1 (endometrial adenocarcinoma) and HOC-21 (ovarian serous cystadenocarcinoma). The incorporation of [14C]amino acids and [3H]uridine into acid-insoluble cell materials in the combination-treated cells was not significantly different from that in cells treated with TNF-alpha or dipyridamole. However, the incorporation of [3H]thymidine was specifically inhibited in all cell lines examined after more than 12 h of the TNF-alpha and dipyridamole combination treatment, although neither agent alone inhibited this incorporation. On the other hand, the growth of tumors induced by the injection of MM-1CB and HMV-1 cells into nude mice was more markedly inhibited by the subcutaneous administration of TNF-alpha in combination with orally administered dipyridamole than by either agent alone. The results presented suggested that dipyridamole is beneficial in assuring the effectiveness of anti-cancer cytokine therapy.
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PMID:Dipyridamole combined with tumor necrosis factor-alpha enhances inhibition of proliferation in human tumor cell lines. 755

Effects of 5-bromo-2-deoxy-uridine (BrdU) and 2-deoxy-D-glucose (2-DG) on 60-Co-gamma-ray induced damage were studied in monolayer cultures of glioma (BMG-1) cells, and PHA-stimulated peripheral leukocytes from normal donors. Micronuclei formation was used as an index of cytogenetic damage. BrdU and 2-DG treatments did not induce micronuclei formation in unirradiated cultures. Presence of BrdU (0.8 microM) for more than one cell cycle (24 hr) significantly increased gamma-ray (1-4 Gy) induced micronuclei formation in exponentially growing BMG-1 cells. Incubation of irradiated cells under sub-optimal growth conditions (DMEM with 1% serum) for 3 hr, instead of growth medium, significantly decreased micronuclei formation. Post-irradiation presence of 2-DG (5 mM; 3 hr, in DMEM + 1% serum) significantly increased radiation damage. In BrdU sensitized cells also, 2-DG significantly increased radiation damage further. In PHA-stimulated leukocytes from normal donors, 2-DG (5mM, equimolar with glucose; for 2 hr) did not increase gamma-ray (2-Gy, 42 hr after PHA-stimulation) induced micronuclei formation. Pre-irradiation presence of BrdU (1.6 microM) significantly increased micronuclei. On the contrary, 2-DG treatment reduced radiation induced micronuclei formation in BrdU sensitized leukocyte cultures. These results suggest that (i) radiation induced lesions leading to micronuclei formation in proliferating tumour cells, are, at least, partly repairable; (ii) combination of 2-DG could reduce BrdU doses required for radiosensitization of proliferating tumour cells; and (iii) 2-DG could differentially increase radiation damage in BrdU sensitized proliferating tumour cells, while reducing manifestation of damage in normal proliferating cells.
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PMID:Differential modification of radiation damage in 5-bromo-2-deoxy-uridine sensitized human glioma cells and PHA-stimulated peripheral leukocytes by 2-deoxy-D-glucose. 781 43

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma x glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [IK(M) or "M-current"] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited IK(M) by 44% and 42%, respectively, at 100 microM. Mean IC50 values were: UTP, 0.77 +/- 0.27 microM; ATP, 1.81 +/- 0.82 microM. The order of nucleotide and nucleoside activity at 100 microM was: UTP = ATP > ATP [gamma S] = ITP > 2-MeSATP > ADP = GTP >> AMP-CPP, adenosine, where ATP[gamma S] is adenosine 5'-O-(3-thiotriphosphate), ITP is inosine 5'-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is alpha, beta methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 microM) or by pre-incubation for 12 h in 500 ng.ml-1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca(2+)-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
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PMID:Activation of nucleotide receptors inhibits M-type K current [IK(M)] in neuroblastoma x glioma hybrid cells. 789 8

Incubation of C6-2B rat glioma cells with UDP or UTP resulted in a time- and concentration-dependent increase in the accumulation of inositol phosphates. In contrast, ATP, ADP, and analogs of these nucleotides known to be effective agonists at P2U-, P2X-, P2Y-, P2T-, and P2Z-purinergic receptors all had no effect on inositol phosphate levels in C6-2B cells. Pyrimidine nucleotides stimulated inositol phosphate accumulation with an order of potency of UDP > 5-BrUTP > UTP > dTDP > UDP glucose. K0.5 values for UDP, 5-BrUTP, and UTP were 2.3 +/- 0.5, 9 +/- 3, and 57 +/- 10 microM, respectively. A similar uridine nucleotide selectivity was observed for arachidonic acid release presumably occurring as a consequence of activation of phospholipase A2. Cross-desensitization and additivity experiments indicated that UDP and UTP interact with the same population of receptors. The effect of uridine nucleotides on inositol phosphate accumulation was inhibited markedly by pretreatment of cells with pertussis toxin. UDP also caused a guanine nucleotide-dependent increase in inositol lipid hydrolysis in streptolysin-O-permeabilized cells. Taken together these results describe the existence of a novel uridine nucleotide receptor that is not activated by adenine nucleotides. This receptor is pharmacologically distinct from the previously described P2U- and other P2-purinergic receptors, and likely is a member of a new class of receptors for extracellular nucleotides.
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PMID:Identification of a uridine nucleotide-selective G-protein-linked receptor that activates phospholipase C. 816 81


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