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 effect of factors released from N2A neuroblastoma cells on the expression of myelin protein genes in glioma C6 cells, i.e., proteolipid protein (PLP) and myelin-associated glycoprotein (MAG), was studied. Both cells lines were propagated in serum-free DMEM-F10 (1:1) medium. The addition of 50% N2A conditioned medium (N2ACM) stimulated the proliferation of C6 cells by approximately 4.5 fold as compared to control cells. The N2ACM-treated cells formed aggregates indicating increased cell-cell affinity. The exposure of C6 cells to N2ACM transiently stimulated the expression of both the MAG-specific and the PLP-specific messages up to eight and four fold over the control values, respectively. The maximal upregulation of the PLP gene occurred two days after N2ACM administration and preceded that of the MAG gene by two days. The effect of N2ACM was dose-dependent in the range of 12.5 to 50%. The secretion of N2A paracrine factors that stimulated the myelin gene expression was also time-dependent. The optimal conditioning time for the release of the PLP gene-stimulating activity was one day, while the maximal MAG gene-stimulating activity was found in the medium conditioned for 3 days. This cellular system may provide a convenient model for studies on trophic neuronal-glial interaction. Furthermore, the results indicate a difference in the regulatory mechanisms between the PLP and the MAG genes.
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PMID:Differential upregulation of PLP and MAG genes in C6 glioma cells by N2A neuroblastoma conditioned medium. 127 70

The effect of ascorbic acid (AA) on rat glioma C6 cells was studied. At physiological AA concentrations of 0.1 and 1 mM, no morphological and no proliferative alterations in the C6 cultures were detectable. Although the total RNA content per cell was not affected by the AA-treatment, AA upregulated the expression of myelin-specific genes, i.e. proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) genes as assessed by northern blot analysis. The steady-state level of the specific mRNAs increased transiently in the AA-treated cells. Three days after AA administration the message level reached a maximum of 10- and 2-fold over control for the PLP and MAG genes, respectively. The upregulation of the genes was directly related to AA concentration. The present data indicate a possible involvement of AA in the regulation of myelin gene activity in the CNS.
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PMID:Ascorbic acid upregulates myelin gene expression in C6 glioma cells. 127 71

The effect of retinoic acid (RA) on the expression of myelin-specific genes, i.e., proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) in rat glioma C6 cells, was analyzed by Northern blot hybridization. RA-treatment increased the steady-state level of the PLP-specific messages within one day after RA administration and the upregulation reached a maximum on the third day. Concomitantly, the expression of MAG-specific messages in the RA-treated C6 cells dropped below the detectability limit. The expression of the PLP gene was directly related to the RA concentration increasing to approximately 44-fold over the control (untreated cells) level at 10(-6) M RA. The stimulatory effect was vitiated by cycloheximide indicating the involvement of intermediate genes in the PLP gene activation. The total cellular RNA content and the level of cyclophilin mRNA was not changed by the RA-treatment. The present data indicate that RA can be a potent modulator of the myelin-specific gene expression. Furthermore, the reciprocal response of PLP versus MAG genes to RA demonstrates that these two genes utilize different regulatory mechanisms.
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PMID:Retinoic acid-regulated expression of proteolipid protein and myelin-associated glycoprotein genes in C6 glioma cells. 137 82

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

The effects of culture conditions on the expression of myelin-specific genes, i.e. proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) in rat glioma C6 cells was studied. Early passage (40-46) cells had higher steady-state level of PLP- and MAG-specific mRNA than late (100) passage cells when grown in defined (serum-free) medium. The PLP gene expression was increased whereas the MAG gene expression was reduced in the presence of 10% fetal calf serum in either passage. The level of both PLP- and MAG-specific messages was also directly related to the cell density indicating cell contact-induced stimulation of the gene expression. Furthermore, the cells apparently secrete factors into the medium, which upregulate the gene expression in autocrine fashion. The results also indicate a dissimilarity of regulatory mechanisms involved in the expression of the PLP and MAG genes.
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PMID:Effect of culture conditions on PLP and MAG gene expression in rat glioma C6 cells. 172 86

The effect of dexamethasone on the expression of proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) genes was investigated in rat C6 glioma cells. The steady state level of the respective mRNAs was quantitated by Northern blot analysis. The treatment of cells with dexamethasone transiently upregulated the expression of both genes with peak mRNA levels of approximately 10-fold over control levels occurring at day 3 for the PLP gene and at day 5 for the MAG gene. The effect was directly related to the drug concentration in the range from 10(-9) to 10(-5) M. Combined exposure of the cells to dexamethasone and retinoic acid featured an additive effect on PLP gene expression, whereas MAG gene expression was depressed below detectability level. The dissimilarity in the response of the genes to dexamethasone and retinoic acid supports the contention that the genes are controlled by different mechanisms. Furthermore, the results indicate that the effects of dexamethasone and retinoic acid on the myelin genes are mediated by different regulatory pathways.
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PMID:Glucocorticoid-induced upregulation of proteolipid protein and myelin-associated glycoprotein genes in C6 cells. 751 49

The treatment of rat glioma C6 cells with 10 microM isoproterenol (Ipt) for 4 days upregulated the expression of the myelin-associated glycoprotein (MAG) gene by approximately 55-fold over the control value. The constant presence of Ipt in the medium was required for the maximal upregulation, as time-restricted exposures to the drug produced only partial, or no upregulation of the gene. No difference in the MAG mRNA stability could be detected in Ipt-treated vs untreated cells indicating that the drug upregulates the MAG gene at transcriptional level. Serum (FCS) strongly attenuated the response of the MAG gene to Ipt. The stimulatory effect of Ipt was profoundly reduced by spermine and H-89, indicating that protein kinase A-dependent protein phosphorylation is involved in the MAG gene activation. Within 30 min after Ipt administration, the c-fos gene was upregulated by 10-fold, and thereafter, its message level decreased and stabilized at approximately 3-fold over control. In contrast, the c-jun gene was downregulated to approximately 20% of control within 30 min after Ipt administration. Subsequently, its message level rose and fell once again within 12 h to approximately half of control, and returned to control level within 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcriptional regulation of myelin associated glycoprotein gene expression by cyclic AMP. 751 73

The methylation status of a 4.4-kb 5' end of the myelin-associated glycoprotein (MAG) gene was assessed in cells with different levels of transcriptional activity of the gene, i.e., liver, brain, O-2A oligodendrocyte precursors cells, mature oligodendrocytes, and glioma C6 cells. Purified DNA was digested with methylation-sensitive restriction enzymes, and the cuts were mapped by the indirect end-labeling technique. The restriction sites within the 4.4-kb fragment revealed a highly heterogenous methylation pattern among cells and tissues, and liver DNA was the most heavily methylated. Most of the restriction sites were partly demethylated in the nervous system cells. Notably, two adjacent Hha1 sites at +94 and +96 were fully methylated in liver, but partially demethylated in the brain, OL, and O2A. Two Hpa2 site located at -1836 and at -39 were progressively demethylated in oligodendrocyte lineage cells, indicating specific hypomethylation associated with the oligodendrocytic differentiation. Most of the restriction sites were weakly methylated in the DNA from neoplastic C6 cells, although the Hha1 sites were fully methylated. No clear-cut correlation between the extent of CpG dinucleotide methylation and the chromatin conformation was found. For example, out of four heavily methylated sites only two comapped with MNase hypersensitive sites. Also, the -1836 Hpa2 site whose demethylation is concomitant with oligodendrocytic differentiation seems to be localized within precisely positioned nucleosomal arrays of the MAG gene chromatin. The results indicate that the MAG gene undergoes progressive demethylation concomitant with the oligodendrocyte differentiation/maturation. However, certain CpG dinucleotides remain heavily methylated even in the fully active gene in mature oligodendrocytes, indicating that they may be essential in maintaining proper chromatin structure.
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PMID:Differentiation-specific demethylation of myelin associated glycoprotein gene in cultured oligodendrocytes. 753 22

Calpain, a Ca2+-activated cysteine protease, has been implicated in apoptosis of immune cells. Since central nervous system (CNS) is abundant in calpain, the possible involvement of calpain in apoptosis of CNS cells needs to be investigated. We studied calpain expression in rat C6 glioma cells exposed to reactive hydroxyl radical (.OH) [formed via the Fenton reaction (Fe2++H2O2+H+-->Fe3++H2O+.OH)], interferon-gamma (IFN-gamma), and calcium ionophore (A23187). Cell death, cell cycle, calpain expression, and calpain activity were examined. Diverse stimuli induced apoptosis in C6 cells morphologically (chromatin condensation as detected by light microscopy) and biochemically [DNA fragmentation as detected by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay]. Oxidative stress arrested a population of C6 cells at the G2/M phase of cell cycle. The levels of mRNA expression of six genes were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR). Diverse stimuli did not alter beta-actin (internal control) expression, but increased calpain expression, and the upregulated bax (pro-apoptotic)/bcl-2 (anti-apoptotic) ratio. There was no significant increase in expression of calpastatin (endogenous calpain inhibitor). Western blot analysis showed an increase in calpain content and degradation of myelin-associated glycoprotein (MAG), a calpain substrate. Pretreatment of C6 cells with calpeptin (a cell-permeable calpain inhibitor) blocked calpain overexpression, MAG degradation, and DNA fragmentation. We conclude that calpain overexpression due to.OH stress, IFN-gamma stimulation, or Ca2+ influx is involved in C6 cell death, which is attenuated by a calpain-specific inhibitor.
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PMID:Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. 1035 May 26

Sialic acids are prominent termini of mammalian glycoconjugates and are key binding determinants for cell-cell recog-nition lectins. Binding of the sialic acid-dependent lectin, myelin-associated glycoprotein (MAG), to nerve cells is implicated in the inhibition of nerve regeneration after injury. Therefore, blocking MAG binding to nerve cell sialoglycoconjugates might enhance nerve regeneration. Previously, we reported that certain sialoglycoconjugates bearing N-acetylneuraminic acid (NeuAc) but not N-glycolylneuraminic acid (NeuGc) support MAG binding (Collins et al., 1997a). We now report highly efficient conversion of sialic acids on living neural cells from exclusively NeuAc to predominantly NeuGc using a novel synthetic metabolic precursor, N-glycolylmannosamine pentaacetate (Man-NGc-PA). When NG108-15 neuroblastoma-glioma hybrid cells, which normally express only NeuAc (and bind to MAG), were cultured in the presence of 1 mM ManNGcPA, they expressed 80-90% of their sialic acid precursor pool as NeuGc within 24 h. Within 5 days, 80% of their ganglioside-associated sialic acids and 70% of their glycoprotein-associated sialic acids were converted to NeuGc. Consistent with this result, treatment of NG108-15 cells with ManNGcPA resulted in nearly complete abrogation of MAG binding. These results demonstrate that ManNGcPA treatment efficiently alters the sialic acid structures on living cells, with a commensurate change in recognition by a physiologically important lectin.
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PMID:Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate: inhibition of myelin-associated glycoprotein binding to neural cells. 1057 Feb 19


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