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)

1. Activity of two glycosyltransferases was studied in retinoic acid-treated C6 cultured glioma cells. 2. The beta-galactoside alpha 2,3-sialyltransferase transferring N-acetylneuramin onto the O-glycans residues of glycoproteins was activated up to twice after chronic treatment (from 24 to 96 hr) with all-trans retinoic acid. 3. No effect was observed for shorter treatments. 4. On the opposite, the N-glycan galactosyltransferase activity remained unchanged whatever the length of retinoic acid treatment was. 5. The activatory effect was not dependent on isomery, as all-trans and 13-cis retinoic acid isomers were both activators of the C6 glioma cell sialyltransferase. 6. Measurement of adhesion of retinoic acid-treated cells using labelled plasma membranes showed an enhancement of adhesion in correlation with enhancement of sialyltransferase activity.
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PMID:Effect of retinoic acid on two glycosyltransferase activities in C6 cultured glioma cells. 212 49

The enzymatic basis for ganglioside regulation during differentiation of NG108-15 mouse neuroblastoma x rat glioma hybrid cells was studied. This cell line contains four gangliosides that lie along the same biosynthetic pathway: GM3, GM2, GM1, and GD1a. Chemically induced neuronal differentiation of NG108-15 cells led to an 80% drop in the steady-state level of their major ganglioside, GM3, a sixfold increase in the level of a minor ganglioside, GM2 (which became the predominant ganglioside of differentiated cells); and relatively little change in the levels of GM1 and GD1a, which lie further along the same biosynthetic pathway. The enzymatic basis for this selective change in ganglioside expression was investigated by measuring the activity of two glycosyltransferases involved in ganglioside biosynthesis. UDP-N-acetylgalactosamine: GM3 N-acetylgalactosaminyltransferase (GM2-synthetase) activity increased fivefold during butyrate-induced differentiation, whereas UDP-galactose: GM2 galactosyltransferase (GM1-synthetase) activity decreased to 10% of its control level. Coordinate regulation of these two glycosyltransferases appears to be primarily responsible for the selective increase of GM2 expression during NG108-15 differentiation.
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PMID:Coordinate regulation of ganglioside glycosyltransferases in differentiating NG108-15 neuroblastoma x glioma cells. 254 Feb 74

A subclone of NG108-15 neuroblastoma-glioma hybrid cells was used to study the intracellular distribution of opioid receptors. Subcellular organelles were separated on self-generating Percoll-sucrose gradients and the enzymes beta-glucuronidase, galactosyltransferase, 5'-nucleotidase, and glucose-6-phosphatase were used as markers to localize the various structures. Analysis of the receptor distribution from untreated cells shows that the plasma membranes contained the highest receptor density, but a significant portion of the opioid binding sites was unevenly distributed between the lysosomes, microsomes, and Golgi elements. The enzyme markers indicated that appearance of opioid receptors in these intracellular structures does not result merely from contamination with plasma membranes. About 11% of the receptors appeared in a fraction lighter than plasma membranes. The antilysosomal agent chloroquine altered the intracellular compartmentation of the receptors, possibly by blocking their translocation in the cells. Leu-enkephalin induced time-dependent loss of receptors from all four intracellular compartments examined, but a kinetic analysis showed that the rate of receptor loss in these fractions was not identical. Thus, the percent of receptors appearing in the lysosomal fraction that could still bind [3H]D-Ala2-D-Leu5-enkephalin in vitro was increased on treatment with Leu-enkephalin. As an additional approach to follow the intracellular fate of the receptors, cells were labeled with [3H]diprenorphine, chased with various unlabeled opiates, and the distribution of 3H-ligand-receptors in the cells was monitored. Leu-enkephalin and etorphine altered the distribution of receptor-bound [3H]diprenorphine between the plasma membranes, lysosomes, and Golgi elements, whereas morphine had no such effect. The study sheds light on the role of intracellular structures in the metabolism of opioid receptors in untreated and opioid-treated cells.
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PMID:Subcellular compartmentation of opioid receptors: modulation by enkephalin and alkaloids. 300 5

Galactosylceramide (galactocerebroside, GalC) and its sulfated derivative, sulfatide, are major lipid components of the central and peripheral nervous system myelin sheath. The enzyme UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.45) catalyzes the final step of galactosylceramide synthesis. In this report we describe isolation of the complete copy of human CGT cDNA. Total RNA from N-370 FG cells, a human fetal glioma cell line, was reverse-transcribed and dG-tailed. Degenerate primers synthesized based on rat CGT cDNA sequence were used in 5'- and 3'- rapid amplification of cDNA ends reaction (RACE). The obtained sequence was used to synthesize the primers for the complete coding region to be amplified and cloned into a pCR 3.1 expression vector. Following transfection of the CHOP cells with the resulting vector, the cell homogenate was assayed for the galactosyltransferase activity. Northern blot hybridization was used to determine the length of CGT mRNA and Southern blot hybridization was used to determine the number of homologous genes. Our results indicate that human CGT retains all conservative features of rat and mouse CGT. It is a single copy gene with mRNA transcript of about 4 kb.
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PMID:Cloning, characterization, and expression of human ceramide galactosyltransferase cDNA. 912 99

The neuroblastoma x glioma NG108-15 hybrid cell line, a widely used model for the study of neuronal differentiation, contains a variety of gangliosides including GM1 and its sialosylated derivative, GD1a. To investigate the role of these a-series gangliotetraose gangliosides in neuritogenesis, we have obtained a mutated subclone of NG108-15 that is deficient in that family of gangliosides. NG108-15 cells were grown in the presence of cholera toxin, which killed the large majority of cells, and from the cholera-resistant survivors we isolated a clone, NG-CR72, that lacks GM1 and GD1a in the plasma and nuclear membranes. GM2 concentration was significantly higher in the plasma membrane. Enzyme assay indicated deficiency of UDP-Gal:GM2 galactosyltransferase (GM1 synthase), which was confirmed by incorporation studies with [3H]sphingosine. These cells resembled wild-type NG108-15 in extending dendritic processes in response to dendritogenic agents (retinoic acid, dibutyryl cAMP) but responded aberrantly to axonogenic stimuli (KCl, ionomycin) by extending unstable neurites that showed the cytoskeletal staining characteristic of dendrites. Moreover, mutant cells treated with the Ca2+ elevating axonogenic agents underwent apoptosis over time, attributed to dysfunction of Ca2+ regulatory mechanisms normally mediated by GM1. Such agents caused dramatic and sustained elevation of intracellular Ca2+ in mutant cells, in contrast to modest and temporary elevation in wild-type cells. Exogenous GM1, inserted into the plasma membrane, had no discernable protective effect on NG-CR72 cells whereas LIGA-20, a membrane-permeant derivative of GM1 that entered both plasma and nuclear membranes, blocked apoptosis, permitted extension of stable neurites, and attenuated the abnormal elevation of intracellular Ca2+.
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PMID:Mutant NG108-15 cells (NG-CR72) deficient in GM1 synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with LIGA-20. 1115 39

beta1,4-galactosyltransferase V (GalT V; EC 2.4.1.38) can effectively galactosylate the GlcNAcbeta1-->6Man arm of the highly branched N-glycans that are characteristic of glioma. Previously, we have reported that the expression of GalT V is increased in the process of glioma. However, currently little is known about the role of GalT V in this process. In this study, the ectopic expression of GalT V could promote the invasion and survival of glioma cells and transformed astrocytes. Furthermore, decreasing the expression of GalT V in glioma cells promoted apoptosis, inhibited the invasion and migration and the ability of tumor formation in vivo, and reduced the activation of AKT. In addition, the activity of GalT V promoter could be induced by epidermal growth factor, dominant active Ras, ERK1, JNK1, and constitutively active AKT. Taken together, our results suggest that GalT V functioned as a novel glioma growth activator and might represent a novel target in glioma therapy.
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PMID:Beta1,4-galactosyltransferase V functions as a positive growth regulator in glioma. 1646 57

In previous study, we have shown that beta1,4-galactosyltransferase V (GalT V) functions as a positive growth regulator in glioma. Here, we reported that down-regulation of the expression of GalT V in SHG44 cells by transfection with antisense cDNA specifically up-regulated the expression of cell surface integrin beta1 without the change of its mRNA, and with integrin beta1 125 kDa mature form increased and 105 kDa precursor form decreased. It is well known that the N-glycans of integrins modulate the location and functions of integrins. The SHG44 cells transfected with antisense cDNA of GalT V demonstrated decreased Golgi localization of integrin beta1, strengthened the interaction between integrin alpha5 and beta1 subunit, and enhanced the adhesion ability to fibronectin and the level of focal adhesion kinase phosphorylation. Our results suggested that the down-regulation of the expression of GalT V could promote the expression of cell surface integrin beta1 and subsequently inhibit glioma malignant phenotype.
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PMID:Down-regulation of the expression of beta1,4-galactosyltransferase V promotes integrin beta1 maturation. 1656 4

Transcription factor E1AF is widely known to play critical roles in tumor metastasis via directly binding to the promoters of genes involved in tumor migration and invasion. Here, we report for the first time E1AF as a novel binding partner for ubiquitously expressed Sp1 transcription factor. E1AF forms a complex with Sp1, contributes to Sp1 phosphorylation and transcriptional activity, and functions as a mediator between epidermal growth factor and Sp1 phosphorylation and activity. Sp1 functions as a carrier bringing E1AF to the promoter region, thus activating transcription of glioma-related gene for beta1,4-galactosyltransferase V (GalT V; EC 2.4.1.38). Biologically, E1AF functions as a positive invasion regulator in glioma in cooperation with Sp1 partly via up-regulation of GalT V. This report describes a new mechanism of glioma invasion involving a cooperative effort between E1AF and Sp1 transcription factors.
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PMID:Functional interaction of E1AF and Sp1 in glioma invasion. 1793 7

Glioma results from unregulated expansion of a self-renewing glioma-initiating cell population. The regulatory pathways which are essential for sustaining the self-renewal of glioma-initiating cells remain largely unknown. Cell surface N-linked oligosaccharides play functional roles in determining cell fate and are associated with glioma malignancy. Previously, we have reported that beta1,4-galactosyltransferase V (beta1,4GalT V) effectively galactosylates the GlcNAcbeta1-->6Man arm of the highly branched N-glycans and positively regulates glioma cell growth. Here, we show that decreasing the expression of beta1,4GalT V by RNA interference in glioma cells attenuated the formation of polylactosamine and inhibited the ability of tumor formation in vivo. Down-regulation of beta1,4GalT V depleted CD133-positive cells in glioma xenograft, and inhibited the self-renewal capacity and the tumorigenic potential of glioma-initiating cells. These data reveal a critical role of beta1,4GalT V in the self-renewal and tumorigenicity of glioma-initiating cells, and indicate that manipulating beta1,4GalT V expression may have therapeutic potential for the treatment of malignant glioma.
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PMID:Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell. 2041 17

One of the most prominent transformation-associated changes in the sugar chains of glycoproteins is an increase in the large N-glycans of cell surface glycoprotein. beta1,4-galactosyltransferase V (beta1,4GalT V) could effectively galactosylate the GlcNAcbeta1-->6 branch which is a marker of glioma. The expression of beta1,4GalT V is increased in the process of glioma development. beta1,4GalT V regulates the invasion, growth in vivo and in vitro of glioma cells. Downregulation of beta1,4GalT V expression increases the sensitivity of malignant glioma cells to DNA damage drugs. Furthermore, beta1,4GalT V regulates Ras and AKT signaling involving in glioma behaviors. Meanwhile, Ras/MAPK and PI3K/AKT signaling pathways are involved in the transcription regulation of beta1,4GalT V gene. E1AF transcription factor, a downstream target of Ras/MAPK and PI3K/AKT signaling pathways, regulates the transcription of beta1,4GalT V in cooperation with Sp1 transcription factor. The contribution of beta1,4GalT V in glioma development is further confirmed in glioma-initiation cells. beta1,4GalT V regulates the self-renewal of glioma-initiation cells. We now present evidence that beta1,4GalT V functions as a positive growth regulator in glioma and might represent a novel target in glioma therapy.
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PMID:Beta1,4-galactosyltransferase V A growth regulator in glioma. 2081 57


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