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)

Receptor binding and cyclic GMP generation by three distinct natriuretic peptides (ANP, BNP, CNP) were studied in a cultured rat glioma cell line (C6). Binding studies revealed the presence of high-affinity binding sites for three natriuretic peptides with almost comparable affinities. In contrast, CNP and BNP were almost equipotent in stimulating intracellular cyclic GMP generation over the low concentration range, but CNP caused further elevation in the high concentration range, whereas ANP was minimally effective. Our data suggest that the glioma cells possess receptors more responsive to CNP than ANP and BNP despite no apparent correlation between receptor binding affinities and cyclic GMP responses.
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PMID:Effects of three distinct natriuretic peptides on receptor binding and guanylate cyclase activities in rat glioma cells. 131 92

Rat glioma C6 cells were stably transfected with a pSV3-neo plasmid containing SV40 T antigen gene, and geniticin-resistant transfectants (designated C6T cells) were cloned. The C6T cells grew as well-defined foci of cells showing squamous or irregular morphology. The doubling time for transfected cells was reduced by approximately 40% as compared to control C6 cells. The transfection with T-antigen also affected the expression of genes coding for structural myelin proteins and for myelin-associated enzymes. The steady-state level of proteolipid protein (PLP)-specific mRNA in C6T cells was 44% lower than in parental C6 cells. On the other hand, the transfection upregulated the expression of myelin-associated glycoprotein (MAG) by 153%. The activity of 2':3' cyclic AMP phosphodiesterase (CNP) was increased by approximately 80% in the C6T cells as compared to untransfected, control cells. The activity of calcium-activated neutral proteinase (CANP) was also significantly elevated in the transfectants by approximately 50% and 220% for millimolar and micromolar form respectively. The results indicate that T antigen affects the expression of myelin genes, although, individual genes appear to be differently regulated implying the existence of several independent regulatory mechanisms.
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PMID:Differential regulation of myelin gene expression in SV40 T antigen-transfected rat glioma C6 cells. 171 91

In an effort to determine the factors that stimulate myelin synthesis, we investigated the mechanism by which dibutyryl cyclic AMP induces the activity of the myelin enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP; EC 3.1.4.37), in C6 glioma cells. Immunotitration experiments and measurements of the accumulation of [35S]methionine-labeled CNP showed that dibutyryl cyclic AMP increased the amount of CNP in the cells but not the catalytic activity per molecule of the enzyme. Moreover, inhibition of protein synthesis with cycloheximide abolished induction of enzyme activity. Dibutyryl cyclic AMP doubled the rate of CNP synthesis but had no effect on the half-life of the enzyme (approximately 33 h). The induction was partially blocked by the inhibitors of mRNA synthesis, cordycepin or alpha-amanitin. Thus, cyclic AMP induces the synthesis of CNP.
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PMID:Induction of myelin components: cyclic AMP increases the synthesis rate of 2',3'-cyclic nucleotide 3'-phosphohydrolase in C6 glioma cells. 298 29

Cyclic AMP (cAMP) is known to induce the activity of the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP; EC 3.1.4.37) in C6 rat glioma cells. This report shows that CNP is also inducible in oligodendrocytes explanted from 1-day-old rat cerebrum and grown in tissue culture. Induction was observed after a 1-day treatment with 1 mM N6, O2-dibutyryl cyclic AMP (dbcAMP) and was maximal after 5 days, reaching 200-240% of control. Induction was observed both in mixed cerebral cell cultures containing oligodendrocytes and astrocytes, and in purified cultures of oligodendrocytes prepared by a differential shakeoff procedure. Addition of dbcAMP to the cultures 3-9 days after the cells were explanted from rat brain induced CNP activity, but no induction was observed when dbcAMP treatment was begun 13 or more days after explanation. These results demonstrate that one component of myelin, CNP, is inducible in oligodendrocytes by a cAMP-mediated mechanism, and suggest a role for cAMP in the regulation of the myelin-associated functions of oligodendrocytes.
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PMID:Cyclic AMP induction of the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase in rat oligodendrocytes. 630 62

We investigated whether the membrane-associated myelin enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP; EC 3.1.4.37), is localized primarily inside the cell or exposed on the cell surface of rat oligodendrocytes and rat C6 glioma cells. Determinations were made by enzyme assays of intact, viable cells vs cells broken by freezing and thawing. Assay of both oligodendrocytes and C6 cells showed that the great majority of the CNP activity was localized inside the cells. Oligodendrocytes were also tested by immunofluorescence staining of unfixed, living cells whose membranes had been made permeable to antibody by fixation. Fixed oligodendrocytes showed intense fluorescence when incubated with rabbit anti-CNP antiserum and fluorescein-conjugated second antibody whereas unfixed cells were not stained. We then tested the possible influence on CNP localization of 3 conditions known to increase CNP specific activity: maturation of oligodendrocytes in vitro during a period when CNP specific activity increases 8-fold or more; growth of C6 cultures to high cell density; and induction of CNP activity in oligodendrocytes and C6 cells by dibutyryl cyclic AMP. Under all conditions, most CNP activity was intracellular. These results show that both the catalytic and major antigenic sites of CNP are localized primarily inside the cell, and suggest an intracellular role for CNP in oligodendrocytes. The results with C6 cells also show that these cells resemble oligodendrocytes with respect to CNP localization.
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PMID:Intracellular localization of 2',3'-cyclic nucleotide 3'-phosphohydrolase in rat oligodendrocytes and C6 glioma cells, and effect of cell maturation and enzyme induction on localization. 632 Sep 68

The functional role of CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase), a minor component of central and peripheral myelin is still unclear. Here we describe preparation of a monoclonal antibody directed against CNP. The antibody, of the immunoglobulin IgG1 type, raised with a basic 46 kDa membrane-associated protein solubilized from pig cerebellar membranes, can be used to detect immunoreactivity in solubilized brain homogenates from pig, mouse, rat, sheep, cow and man, in cerebrum and cerebellum, but not in other tissues such as liver, skeletal and heart muscle. The antibody recognizes the CNP doublet band and shows no cross-reactivity with any of the other brain proteins solubilized. In tissue sections from paraformaldehyde-fixed rat brain the antigen was localized in oligodendrocytes. In cultured glial cells from newborn mice the antibody stained cells which were identified as oligodendrocytes by co-localization of myelin basic protein. Even cells from a C6 rat glioma cell line, which contain very little of CNP, were labeled by the monoclonal antibody. Thus the monoclonal antibody recognizing CNP from several species is suitable for immunocytochemical investigations and also for biochemical studies of CNP, since the antibody has been employed for immunoprecipitation and immunopurification of CNP in crude brain homogenates.
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PMID:Generation of a monoclonal antibody against the myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) suitable for biochemical and for immunohistochemical investigations of CNP. 787 17

The effect of the natriuretic peptides ANP, BNP and CNP on cGMP formation and immediate early gene expression was investigated in PC12 phaeochromocytoma and C6 glioma cell lines. The three natriuretic peptides were shown to rapidly induce c-fos, TIS8/egr-1 and junB mRNA expression in both cell lines, via stimulation of the cGMP pathway. CNP stimulated cGMP formation and gene induction more potently than the other peptides in C6 cells, and this was statistically significant. In contrast, the three peptides produced similar gene induction in PC12 cells, despite the higher cGMP accumulation evoked by ANP or BNP. CNP was also found to increase DNA binding activity of the transcription factor AP1 in both cell types, demonstrating that natriuretic peptides potentially regulate key cellular gene expression.
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PMID:Immediate early gene induction by natriuretic peptides in PC12 phaeochromocytoma and C6 glioma cells. 908 Apr 15

Any variation in CNP and GS activity in vitro under the effect of growth factors with different mechanisms of action, may indicate a general process of differentiation in the culture. An increase in the GS activity in early passage glioma may be interpreted as an induction of the differentiating phenotype involving cell transformation into a more astrocytic-like culture. Hence, under the above experimental conditions, dexamethasone and insulin are the two factors with the most potent differentiating effect on rat C6 glioma cell line. Comparative studies with growth regulators using different receptor pathways and mechanisms of action may add valuable data to the current knowledge in the field. The data presented in this chapter show the plasticity of C6 glioma to the differentiating effect of various growth factors, especially insulin and dexamethasone, and confirms C6 glioma cell line as a useful model for studies on glial cell properties and proliferation in vitro.
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PMID:Steroid and protein regulators of glial cell proliferation. 941 79

It was recently shown that the two transcripts encoding the isoforms of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP1 and CNP2) are differentially regulated during the process of oligodendrocyte maturation. In oligodendrocyte precursors, only CNP2 mRNA is present, whereas in differentiating oligodendrocytes, both CNP1 and CNP2 mRNAs are expressed. This pattern of CNP expression is likely due to stage-specific transcriptional regulation of the two CNP promoters during the process of oligodendrocyte differentiation. Here, we report the influence of increased intracellular cyclic AMP (cAMP) levels on the transcription of both CNP1 and CNP2 mRNAs in rat C6 glioma cells. We found that the transcription of CNP1 mRNA was significantly increased in comparison with that of CNP2 mRNA in cells treated with cAMP analogues to elevate intracellular cAMP levels. This up-regulation of CNP1 expression (a) is due to an increase of transcription, (b) requires de novo protein synthesis, and (c) requires the activity of protein kinase A. These results are physiologically significant and support the idea that a cAMP-mediated pathway is part of the molecular mechanisms regulating the expression of CNP1 in oligodendrocytes. The regulation of CNP1 promoter activity by cAMP was then investigated in stably transfected C6 cell lines containing various deletions of the CNP promoter directing the bacterial chloramphenicol acetyltransferase gene. We showed that the sequence between nucleotides -126 and -102 was essential for the cAMP-dependent induction of CNP1 expression. Gel retardation analysis showed that two protein-DNA complexes are formed between this sequence and nuclear factors from C6 cells treated or not treated with cAMP. This suggests that the induction of CNP1 mRNA transcription is not mediated by changes in binding of nuclear factors that interact directly with the -126/-102 sequence. Sequence analysis of this region revealed the presence of a putative activator protein-2 (AP-2) binding site. It is interesting that mutagenesis of this region resulted in a significant reduction in transcriptional responses to cAMP, implying a possible role for the AP-2 factor in the expression of CNP1. In addition, we have shown that putative binding sites for activator protein-4 and nuclear factor-1 adjacent to the AP-2 site are required for efficient induction of CNP1 expression by cAMP. Taken together, our results show that the cAMP-dependent accumulation of CNP1 mRNA appears to depend on the synergistic interaction of several regulatory elements.
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PMID:Transcriptional regulation of 2',3'-cyclic nucleotide 3'-phosphodiesterase gene expression by cyclic AMP in C6 cells. 1103 83

Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemo-resistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies. Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets, designated type A and type B cultures. The type A cultures displayed high expression of CXCR4, SOX2, EAAT1, and GFAP and low expression of CNP, PDGFRB, CXCL12, and extracellular matrix proteins. Clinical significance of the 2 types was indicated by the expression of type A- and type B-defining genes in different clinical glioblastoma samples. Classification of glioblastomas with type A- and type B-defining genes generated 2 groups of tumors composed predominantly of the classical, neural, and/or proneural subsets and the mesenchymal subset, respectively. Furthermore, tumors with EGFR mutations were enriched in the group of type A samples. Type A cultures possessed a higher capacity to form xenograft tumors and neurospheres and displayed low or no sensitivity to monotreatment with PDGF- and IGF-1-receptor inhibitors but were efficiently growth inhibited by combination treatment with low doses of these 2 inhibitors. Furthermore, siRNA-induced downregulation of SOX2 reduced sphere formation of type A cultures, decreased expression of type A-defining genes, and conferred sensitivity to monotreatment with PDGF- and IGF-1-receptor inhibitors. The present study thus describes a tumor- and neurosphere-forming SOX2-dependent subset of glioblastoma cultures characterized by a gene expression signature similar to that of the recently described classical, proneural, and/or neural subsets of glioblastoma. The findings that resistance to PDGF- and IGF-1-receptor inhibitors is related to SOX2 expression and can be overcome by combination treatment should be considered in ongoing efforts to develop novel stem cell-targeting therapies.
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PMID:Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile. 2194 Jul 38


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