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)

Both the cytosol and membrane in C6 glioma cells express abundance of PKC alpha, delta, zeta and trace amount of PKC epsilon by Western blot analysis with isozyme-specific antibodies. These characteristics make this cell line a good model to study the properties of different classes of PKC isoforms in one cell type. Exposure of the cells to 100 nM TPA for 10 min resulted in the translocation of conventional PKC alpha (cPKC alpha) and new PKC delta (nPKC delta) and -epsilon from the cytosolic to the membrane fraction, while left atypical PKC zeta (aPKC zeta) unaffected. The extent of translocation of cPKC alpha induced by TPA was more prominent than that of nPKC delta and nPKC epsilon. alpha-TPA, the inactive phorbol ester, did not induce translocation of these isozymes. After treatment of the cells with 1 microM TPA for 17 h, cPKC alpha, nPKC delta and nPKC epsilon were almost completely down-regulated, whereas aPKC zeta was still unaffected. The natural activators of this cell line, endothelin-1 and ATP also translocated cPKC alpha and nPKC delta. However, the extent of translocation induced by these two agonists was much less than that of TPA.
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PMID:Protein kinase C alpha, delta, epsilon and zeta in C6 glioma cells. TPA induces translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC zeta. 840 36

An 80-kDa protein labeled with [3H]myristic acid in C6 glioma and N1E-115 neuroblastoma cells has been identified as the myristoylated alanine-rich C kinase substrate (MARCKS protein) on the basis of its calmodulin-binding, acidic nature, heat stability, and immunochemical properties. When C6 cells preincubated with [3H]myristate were treated with 200 nM 4 beta-12-O-tetradecanoylphorbol 13-acetate (beta-TPA), labeled MARCKS was rapidly increased in the soluble digitonin fraction (maximal, fivefold at 10 min) with a concomitant decrease in the Triton X-100-soluble membrane fraction. However, phosphorylation of this protein was increased in the presence of beta-TPA to a similar extent in both fractions (maximal, fourfold at 30 min). In contrast, beta-TPA-stimulated phosphorylation of MARCKS in N1E-115 cells was confined to the membrane fraction only and no change in the distribution of the myristoylated protein was noted relative to alpha-TPA controls. These results indicate that although phosphorylation of MARCKS by protein kinase C occurs in both cell lines, it is not directly associated with translocation from membrane to cytosol, which occurs in C6 cells only. The cell-specific translocation of MARCKS appears to correlate with previously demonstrated differential effects of phorbol esters on stimulation of phosphatidylcholine turnover in these two cell lines.
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PMID:Dissociation of phosphorylation and translocation of a myristoylated protein kinase C substrate (MARCKS protein) in C6 glioma and N1E-115 neuroblastoma cells. 845 32

The cell surface sugar determinants (CSSD) were examined in C6 glioma cells in cultures at different conditions of growth by peroxidase conjugates of the lectins: peanut agglutinin (PNA), Ricinus communis agglutinin (RCA), Helix pomatia agglutinin (HPA), wheat germ agglutinin (WGA), lentil agglutinin (LCA), laburnum bork agglutinin (LABA), and lotus agglutinin (TPA). It was found that the cells bound more intensively WGA, LCA, and RCA compared to PNA, HPA; the weakest staining was provided by LABA and TPA. Binding intensity for PNA significantly increased after pretreatment of the cells with neuraminidase. This indicates that a part of the beta-D-galactose residues on the surface membrane of C6 glioma cells is covered by sialic acid. The process of sialization was increased during the culturing of C6 glioma cells. Addition of cis-DDP or dBcAMP to cultures growing in medium with 10% of CS increased the number of Gal residues which are not covered by sialic acid. The expression of beta-D-galactose (Gal), N-acetyl-D-galactosamine (NAcDGal), and fucose (Fuc) residues appeared to be most responsive to changes in growth conditions and degree of cell differentiation. The expressions of N-acetyl-D-glucosamine (NAcDGlc) and mannose (Man) residues were high and seems did not depend on changing of the conditions of culturing. In C6 glioma cells cultures in which the rate of cell division, formation of the cell processes, and adhesiveness of the cells to the substratum were reduced by growing cells in MEM+, expression of beta-Gal, NAcDGal, and Fuc was considerably reduced. The decrease of expression of beta-Gal, NAcDGal, and Fuc on the surface of cell membrane was more pronounced in MEM+ with 1% of CS than in MEM+ with 10% of CS. In DbcAMP and cis-DDP treated cultures, grown in medium with 1% serum, in which cell division was inhibited without obvious changes in cell adhesiveness to the substratum, binding of PNA and HPA was increased due to higher expression of beta-Gal and NAcDGal. From these observations it was concluded that the pattern of expression of sugar residues on the cell surface varies according to the biological state of the cells and are easily affected by tissue culture conditions.
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PMID:Growth related changes in sugar determinants on the surface of C6 glioma cells in culture: a cytochemical lectin-binding study. 856 19

Phosphatidylcholine (PtdCho) can provide lipid second messengers involved in signal transduction pathways. As a measure of phospholipid turnover in response to extracellular stimulation, we investigated differential enhancement of [3H]choline incorporation into PtdCho by phorbol esters. In C6 rat glioma and SK-N-SH human neuroblastoma cells, [3H]PtdCho synthesis was 2-4 fold stimulated by beta-12-O-tetradecanoylphorbol-13-acetate (beta-TPA) when [3H]choline was incubated simultaneously with, or 15 min prior to, beta-TPA treatment. By contrast, in N1E-115 mouse and SK-N-MC human neuroblastoma cells, phorbol esters had no appreciable effect on [3H]choline incorporation; however, in all cells, 200 microM oleic acid enhanced PtdCho synthesis, indicating a stimulable process. Alterations by thymeleatoxin (TMT), an activator of conventional PKC isoforms (alpha, beta and gamma), were similar to beta-TPA. We investigated whether expression of specific PKC isoforms might correlate with these effects of phorbol esters on PtdCho synthesis. All cell lines bound phorbol esters, had PKC activity that was translocated by phorbol esters and differentially expressed isoforms of PKC. Northern and western blot analyses, using specific cDNA and antibodies for PKC-alpha, -beta, -gamma, -delta, -epsilon, and -zeta, revealed that expression of alpha-isoform predominated in C6 and SK-N-SH cells. In contrast, TPA-responsive beta-isoform predominated in SK-N-MC cells. gamma-PKC was not detected in any cells and only in C6 cells was PKC-delta present and translocated by beta-TPA treatment. PKC-epsilon was not detected in SK-N-MC cell lines but translocated with TPA treatment in the other three cell lines. PKC-zeta was present in all cells but was unaltered by TPA treatment. Accordingly, stimulation of PtdCho turnover by phorbol esters correlated only with expression of PKC-alpha; presence of PKC-beta alone was insufficient for a TPA response.
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PMID:Phorbol ester stimulation of phosphatidylcholine synthesis in four cultured neural cell lines: correlations with expression of protein kinase C isoforms. 878 1

Neuroblastoma and glioma cells differentially express isoforms of protein kinase C (PKC) and myristoylated PKC substrates (e.g. MARCKS). Correlation with metabolism of membrane phospholipids suggests that PKC-alpha and MARCKS may be required to mediate phosphatidylcholine turnover stimulated by phorbol ester (beta-TPA). To evaluate relationships to neural cell differentiation, SK-N-SH human neuroblastoma cells were treated with 20 nM beta-TPA. In beta-TPA-treated cells, growth arrest and differentiation occurred (neurite extension; 40-60% decrease in cell number, total protein and RNA). By day 4, mRNA for PKC-alpha and MARCKS increased and, after an initial decrease, PKC-alpha protein also increased. At day 4, phosphatidylcholine synthesis was 3-5 fold greater than in control cells. In contrast, C6 glioma cells treated with beta-TPA showed no growth arrest, decreased PKC-alpha protein (< 20%) and lower phosphatidylcholine synthesis. Thus, induced differentiation of human neuroblastoma cells involved increased expression of PKC-alpha and MARCKS and synthesis of phosphatidylcholine, consistent with involvement of PKC-alpha and MARCKS in regulation of phosphatidylcholine turnover during neurite growth.
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PMID:Protein kinase C isoforms and growth, differentiation and phosphatidylcholine turnover in human neuroblastoma cells. 890 63

The invasion/migration of two cell lines, melanoma (MEW) and glioma (BT5C), and their counterparts treated for prolonged time with TPA were studied. On Western blots both cell lines expressed alpha, beta I protein kinase C isoforms, whereas beta II and gamma were not detected. The down-regulation of alpha and beta I PKC was observed in glioma cells after long treatment with TPA, whereas the same treatment of melanoma cells did not lead to PKC downregulation. The down-regulation of PKC was accompanied by stimulation of cell migration/invasion through Transwell chambers coated with collagen IV or fibronectin. In the case of melanoma cells treated with TPA, whose PKC was not down-regulated, the inhibition of migration/invasion was observed. The invasive properties of studied cells did not correlate with any conventional PKC isoform expression.
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PMID:The pleiotropic effect of TPA on in vitro invasion/migration of glioma and melanoma cell lines. 894 14

The in-vitro effects of human interferon alpha-2b (HuIFN alpha-2b), protein kinase C (PKC) agonist [TPA (12-0-tetra-decanoyl-phorbol-13-acetate)] and PKC inhibitor (calphostin C) on human glioma (U-373 MG) PKC activity, cell proliferation and cell cycle were compared. HuIFN alpha-2b and TPA increased PKC activity, elevated the number of cells in DNA synthesis (S) phase and decreased cell proliferation by similar magnitudes. Calphostin C inhibited PKC activity, increased the number of cells in S phase and produced strong cytotoxic effects (IC50 150 nM). Higher concentrations of calphostin C with or without serum induced an additional block in gap2 and mitosis. We conclude that HuIFN alpha-2b's mode of action may be directly or indirectly affecting PKC. The response produced by HuIFN alpha-2b is similar to TPA (potent PKC activation and S phase arrest).
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PMID:Effects of interferon and PKC modulators on human glioma protein kinase C, cell proliferation, and cell cycle. 923 28

Hydrolysis of phosphatidylcholine (PtdCho) can provide lipid second messengers involved in sustained signal transduction. Four neural-derived cell lines (C6 rat glioma; N1E-115 mouse and SK-N-MC and SK-N-SH human neuroblastoma) express different protein kinase C (PKC) isoforms and differentially respond to 4beta-12-O-tetradecanoylphorbol-13-acetate (beta-TPA)-stimulation of PtdCho synthesis. We examined involvement of PLD and PKC in the hydrolysis and resynthesis of PtdCho and phosphatidylethanolamine stimulated by beta-TPA, bryostatin (a non-phorbol PKC activator) and oleic acid (18:1n-9) in the four cell lines. beta-TPA or bryostatin produced similar enhancement of [3H]Cho incorporation, loss of stimulated synthesis after down regulation of PKC, and activation of PLD. In C6 cells, staurosporine (STS) and bis-indolylmaleimide (BIM) only partially inhibited basal and beta-TPA-stimulated PLD activity measured as choline or ethanolamine release; phosphatidylbutanol formation after prelabeling with [9,10-3H]18:1n-9, [9,10-3H]myristic acid (14:0), [1-14C]eicosapentaenoic acid (20:5n-3) or 1-O-[alkyl-1', 2-3H]-sn-glyceryl-3-phosphorylcholine gave similar results. STS at >200 nM activated PLD in the presence or absence of beta-TPA. In SK-N-SH cells where PtdCho synthesis was stimulated by beta-TPA or bryostatin, no effect of these agents on PLD was observed. 18:1n-9 stimulated PtdCho synthesis and, to a lesser extent, hydrolysis by PLD both with and without beta-TPA present. Fatty acids had no effect on PKC activities and down regulation of PKC with beta-TPA enhanced fatty acid stimulation of PtdCho synthesis. Thus, activation of PLD hydrolysis preceding resynthesis is involved in the stimulatory effects of beta-TPA on PtdCho synthesis in some but not all of these neural derived cells. Further, PLD hydrolysis of PtdCho and PtdEtn appear to have differing aspects of regulation. Fatty acid regulation of PtdCho synthesis occurs independent of PKC activation. Accordingly, regulation of membrane phospholipid degradation and resynthesis in association with lipid second messenger generation can involve a complex interplay of PLD, PKC, and fatty acids. (c) 1998 Elsevier Science B.V.
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PMID:Involvement of phospholipase D and protein kinase C in phorbol ester and fatty acid stimulated turnover of phosphatidylcholine and phosphatidylethanolamine in neural cells. 948 44

Malignant gliomas are the most common primary intracranial neoplasms in adults and are largely refractory to post-surgical therapy despite intensive therapeutic efforts. Using a number of different brain tumor-derived cell lines we have demonstrated that the mRNA for osteopontin (OPN), which is substantially over-expressed by some tumors in comparison with normal tissues, is preferentially expressed in high grade and metastatic brain tumors compared to low grade brain tumors. One glioma-derived cell line, U105MG, which does not express significant amounts of OPN mRNA, could be induced dose-dependently by the tumor-promoting and PKC-activating phorbol ester, TPA, to over-express OPN mRNA in a PKC-dependent manner. Unexpectedly, treatment of U105MG cells with Ca2+ ionophore (A23187) completely inhibited TPA-mediated induction of OPN while treatment with the intracellular Ca2+ antagonist TMB-8 had no significant effect. Elucidation of regulatory mechanisms for OPN induction in glioma cells should facilitate rational design of novel therapeutics for human malignant gliomas.
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PMID:TPA-mediated regulation of osteopontin in human malignant glioma cells. 961 23

In has been found that sphingosine, propranolol, imipramine and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) have a stimulatory effect on phospholipase D activity in glioma C6 cells. The cells were prelabelled with [1-(14)C]palmitic acid and phospholipase D-mediated synthesis of [(14)C]phosphatidylethanol was measured. The enhancing effect of TPA was almost completely blocked by a specific protein kinase C inhibitor, GF 109203X. In contrast, GF 109203X failed to inhibit the sphingosine, imipramine and propranolol stimulatory effects, indicating that their stimulation was independent of protein kinase C. The effect of TPA on phospholipase D was also blocked by imipramine and propranolol, whereas sphingosine additively potentiated TPA-mediated phospholipase D activity, both at shorter and longer (2-60 min) times of incubation. These results suggest that in glioma C6 cells, sphingosine is not only involved in a different phospholipase D activation than the TPA regulatory system, but also that it operates in a different compartment of the cell.
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PMID:Different regulation of phospholipase D activity in glioma C6 cells by sphingosine, propranolol, imipramine and phorbol ester. 1088 69


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