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)

Northern blot analysis of human tissues has demonstrated the expression of the brain-type glucose transporter isoform (GLUT 3) in liver, muscle and fat, raising the possibility that this transporter isoform may play a role in the regulation of glucose disposal in these tissues in response to insulin. We have raised an anti-peptide antibody against the C-terminal 13 amino acids of the murine homologue of this transporter isoform, and determined its tissue distribution in mouse tissues and murine-derived cell lines. The antibodies recognise a glycoprotein of about 50 kilodaltons, expressed at high levels in murine brain. In contrast to human tissues, the expression of GLUT 3 in mice is restricted to the brain, and no immunoreactivity was observed in either liver, fat or muscle membranes, or in murine 3T3-L1 fibroblasts or adipocytes. In contrast, high levels of expression of this isoform were observed in the NG 108 neuroblastoma x glioma cell line, a hybrid cell derived from rat glioma and mouse neuroblastoma cells. Taken together, these data suggest that the expression of GLUT 3 in rodents is restricted to non-insulin responsive neuronal cells and hence it is likely that the factors regulating the expression of this transporter in rodents differ to those in humans.
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PMID:Expression of the brain-type glucose transporter is restricted to brain and neuronal cells in mice. 151 57

The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone-induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 +/- 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 +/- 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 +/- 10.5%), lower vascular density (102 +/- 64 vessels/mm2), and smaller tumor size (control cross-sectional area, 17.0 +/- 3.4 mm2; treated, 4.6 +/- 1.0 mm2). Essentially all vessels became GLUT1-positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive.
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PMID:Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids. 159 83

Regulation of glucose uptake by an astroglial cell secreted factor(s) was studied in primary cultures of brain microvessel endothelial cells (BMECs). Uptake of a non-metabolizable glucose analog, 3-O-[3H]methyl-D-glucose ([3H]3MG), was measured after the BMECs were treated with media conditioned by primary cultures of rat astrocytes (Astrocyte Conditioned Media: ACM) or rat C6 glioma cells (Glioma Cell Conditioned Media: GCM). Uptake of [3H]3MG was significantly increased by ACM (30-50%) and GCM (60-200%) treatments, whereas conditioned medium from 3T3 fibroblasts (3T3) caused no significant effect. The elevation in [3H]3MG uptake increased with increasing time of exposure of BMECs to these conditioned media (CM), and the effect was shown to be reversible. Glucose depletion of CM was shown not to be a factor. The presence of cycloheximide, a protein synthesis inhibitor, during treatment of the BMECs with ACM and GCM blocked the increase in [3H]3MG uptake by the cells. These results suggested that ACM or GCM treatment elevated de novo synthesis of brain-type glucose transporter (GLUT1). Indeed, enhanced GLUT1 expression by these treatments in BMECs was demonstrated directly by enzyme-linked immunosorbent assay (ELISA) using antibodies against human GLUT1. After trypsinization of ACM and GCM, both conditioned media still induced significant stimulation of [3H]3MG uptake by BMECs. A significant increase in [3H]3MG uptake was also observed when ACM or GCM was exposed to BMECs through a dialysis membrane with a molecular weight cutoff of 1000. To examine whether the effects were specific to brain endothelial cells, [3H]3MG uptake experiments were performed employing aortic endothelial cells (AECs), pulmonary microvessel endothelial cells (PMECs), and 3T3 cells. ACM treatment did not alter 3MG uptake by these cells, suggesting that the ACM effect was specific to BMECs. On the other hand, [3H]3MG uptake by AECs and PMECs treated with GCM was significantly enhanced. The present study demonstrated that some factor(s) of relatively small molecular weight, which was released from astrocytes or glioma cells, stimulated glucose uptake by enhancing GLUT1 synthesis in BMECs.
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PMID:Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. II. Effects of conditioned media from astroglial and glioma cells. 175 16

GLUT3 glucose transporter gene expression is confined to neurons, while GLUT1 gene expression is limited to endothelial cells in normal brain. Thus far, neither of the GLUT genes has been shown to be consistently expressed in glial cells in adult brain in vivo under normal conditions. However, GLUT gene expression may be aberrant in human brain glial tumors. The present investigation shows that the GLUT1 and GLUT3 transcripts are differentially expressed in a series of 20 human brain tumors. The GLUT1/actin mRNA ratio increased in parallel to the astrocytoma grade, compared to a control human brain cortex, although no change in this ratio was seen in 5 meningiomas. Immunoreactive GLUT1 protein was not detectable in human brain tumors, including high-grade gliomas. Both 4.2 or 2.7 kb GLUT3/actin mRNA ratios showed a linear correlation with the glioma grade (P < 0.025), and the GLUT3-immunoreactive protein was also expressed in high grade gliomas. These studies provide evidence for induction of GLUT1 and GLUT3 gene expression in malignant glial cells, and the mRNA levels correlate with the biologic aggressiveness of the tumor. The detection of immunoreactive GLUT3, but not GLUT1, in the high grade gliomas suggest the GLUT3 isoform may be the predominant glucose transporter in highly malignant glial cells of human brain.
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PMID:Gene expression of GLUT3 and GLUT1 glucose transporters in human brain tumors. 787 54

The blood-brain barrier GLUT1 glucose transporter is localized in brain to the capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo. However, its expression is markedly downregulated in cultured bovine brain capillary endothelium (ECL cells), possibly due to the absence of brain-derived or astrocyte trophic factors in the tissue culture medium. To examine this hypothesis, we studied the effect of a bovine brain homogenate (BBH), and conditioned media and plasma membranes obtained from the rat C6 glioma cell line, on the abundance of the GLUT1 transcript in ECL cells. BBH induced a significant increase in the abundance of both GLUT1 and actin mRNAs, and this effect was dose and time dependent. The increase in the GLUT1 mRNA levels correlated with an increase in the transcriptional rate of this gene measured by nuclear run-on experiments. C6 conditioned media and C6 plasma membranes had no effect on the abundance of either GLUT1 or actin mRNA. To determine whether known growth factors cause BBH-like induction of GLUT1 and actin mRNAs, a series of growth factors was also tested. EGF and PDGF had no effect on the levels of these mRNAs. Basic FGF had a moderate effect and TNF alpha partially mimicked the effect of BBH on both GLUT1 and actin transcripts. The present data suggests that brain-derived trophic factors present in BBH stimulate BBB-GLUT1 glucose transporter gene expression in ECL cells through a transcriptional mechanism. Although this effect was partially mimicked by TNF alpha, C6 cell membranes or C6 conditioned media were unable to induce changes in the abundance of GLUT1 mRNA. Therefore, BBH may be a useful model to study the characterization of soluble brain-derived trophic factors involved in the induction of BBB-GLUT1 gene expression.
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PMID:Enhanced expression of the blood-brain barrier GLUT1 glucose transporter gene by brain-derived factors. 801 84

The posttranscriptional regulation of glucose transporter GLUT1 gene expression may be mediated by specific interactions of cytosolic proteins and regulatory cis-elements within the untranslated regions (UTRs) of the GLUT1 mRNA. These putative cis/trans interactions were examined in the present studies with RNase T1 protection assays using 32P-labeled GLUT1 3'-UTR prepared from transcription plasmids and cytosolic proteins from C6 rat glioma cells. RNase T1 mapping studies localized a cis-element to nucleotides 2,170-2,207 on the bovine GLUT1 mRNA 3'-UTR. Ultraviolet cross-linking of RNA/protein complexes identified two complexes having molecular masses of 88 and 44 kDa. Competition studies with synthetic RNA and oligodeoxynucleotides showed the 88-kDa complex reacted with nucleotides 2,180-2,197 and that the 44-kDa complex reacted with sequences within nucleotides 1,717-2,132 of the bovine GLUT1 mRNA. The GLUT1 3'-UTR between nucleotides 2,100 and 2,300 was generated by polymerase chain reaction and subcloned at a unique Pfl/MI site within the 3'-UTR of a luciferase gene within the mammalian expression vector pGL2. Transfection of C6 rat glioma cells with the luciferase expression vector containing this portion of the GLUT1 3'-UTR resulted in a sixfold increase in luciferase gene expression in C6 cells. The identification of these cis/trans mechanisms provides support for the hypothesis that the posttranscriptional regulation of GLUT1 gene expression may be mediated by the interaction of specific cytosolic proteins with the GLUT1 mRNA 3'-UTR.
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PMID:Cis-element/cytoplasmic protein interaction within the 3'-untranslated region of the GLUT1 glucose transporter mRNA. 859 13

In order to establish whether growth of glioma cells is associated with glucose transport and metabolism, we investigated expression of the glucose transporter and hexokinase, as well as glucose transport and glucose phosphorylation in rat C6 glioma cells growing at different rates. Rat C6 glioma cells were subcloned to produce four different cell lines (CL1, CL2, CL3 and CL4) differing in growth, differentiation and morphology: CL1 cells were slow-growing with an astrocytic appearance whereas CL4 cells grew rapidly and were small and spindle-shaped. Immunocytochemical analysis using glial fibrillary acidic protein and galactocerebroside antibodies revealed that CL1 and CL4 cells differentiate to astrocytes and oligodendrocytes respectively. Both of these cell lines expressed GLUT1 mRNA predominantly, whereas little GLUT3 mRNA was evident by Northern-blot analysis. The GLUT1 mRNA level was much higher in CL4 than in CL1 cells, and the uptake of 2-deoxy-D-glucose and 3-O-methyl-D-glucose by CL4 cells was markedly higher than that by CL1 cells, indicating a correlation between the growth rate, glucose transporter (GLUT1) level and glucose-transport rate of C6 glioma cells. We then studied glucose metabolism by CL1 and CL4 cells by measuring their hexokinase activities and intracellular concentrations of glucose and ATP. The mitochondrial hexokinase activity of CL4 cells was about three times higher than that of CL1 cells, whereas the cytosolic hexokinase activity of CL4 cells was only about half that of CL1 cells. As the total amount of cellular hexokinase protein in CL4 cells was only slightly higher (about 20%) than that in CL1 cells, the hexokinase protein of CL4 cells was considered to have moved from the cytosol to the mitochondrial membranes. Consistent with the increased mitochondrial hexokinase activity of CL4 cells, the intracellular glucose concentration was undetectable, and the ATP concentration was higher than that of CL1 cells, suggesting that glucose transport is the rate-limiting factor for overall glucose metabolism is rapidly growing C6 cells. Therefore the present data demonstrate that glioma cell growth is related to glucose transport, which is closely associated with glucose metabolism.
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PMID:Rat C6 glioma cell growth is related to glucose transport and metabolism. 891 84

The posttranscriptional regulation of GLUT1 glucose transporter gene expression may be mediated by specific interactions between cytosolic trans-acting factors and regulatory cis-elements within the 3'-untranslated regions (UTRs) of the GLUT1 mRNA. Recent studies demonstrate that experimental and human brain tumors express an 80-kDa protein that reacts with a specific sequence around nucleotide 2,200 within the GLUT1 mRNA 3'-UTR. The 80-kDa protein is selectively expressed in hemangioblastoma, a tumor characterized by overexpression of GLUT1. The enhancer role of this GLUT1 3'-UTR cis-element was confirmed in the present studies using the luciferase expression vector pGL2 and site-directed deletion. Transfection of C6 glioma cells with pGL2 (containing nucleotides 2,100-2,300 of the bovine GLUT1 3'-UTR inserted at the Pfl MI site within the luciferase 3'-UTR) results in a fivefold increase in luciferase gene expression. Deletion of nucleotides 2,181-2,190 of the bovine GLUT1 3'-UTR, i.e., the putative binding site of the 80-kDa protein, completely eliminated the enhancement of luciferase activity in the transfected cells. Luciferase mRNA containing the putative cis-element inserted in the 3'-UTR was transcribed, and after UV crosslinking, this mRNA complexed with the 80-kDa protein in cytosol of either C6 cells or hemangioblastoma. In contrast, this complex was undetected with either luciferase control mRNA or 10 nucleotide-deleted RNA. The present study provides evidence that nucleotides 2,181-2,190 of the bovine GLUT1 mRNA 3'-UTR forms a complex with brain tumor cytosolic proteins that serves to increase GLUT1 gene expression at the posttranscriptional level.
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PMID:Site-directed deletion of a 10-nucleotide domain of the 3'-untranslated region of the GLUT1 glucose transporter mRNA eliminates cytosolic protein binding in human brain tumors and induction of reporter gene expression. 916 56

The role of G proteins in glucose uptake was investigated using C6 glioma cells. Carbachol (an agonist acting via G protein coupled receptors) and 5'-guanylylimidodiphosphate (Gpp(NH)p; a nonhydrolysable guanine nucleotide analog which bypasses the receptors and directly activates G proteins) stimulated [3H]2-deoxy-D-glucose (2DG) uptake by C6 cells, suggesting that hexose uptake is a G protein-mediated process. To identify the G protein involved in glucose uptake by C6 cells, the effect of carbachol on 2DG uptake was examined in the presence of pertussis toxin. Pertussis toxin treatment did not alter the ability of C6 cells to respond to carbachol, ruling out the involvement of G(i alpha) in 2DG uptake. C6 cells were transfected with G(q alpha) or GLUT1 cDNA for 48 h, exposed to 1 mM carbachol for 2 h, and processed for 2DG uptake. Carbachol stimulated 2DG uptake in both G(q alpha) and GLUT1-transfected cells. Gpp(NH)p, also stimulated 2DG uptake in G(q alpha) and GLUT1-transfected cells. These results suggest that muscarinic receptor coupling to G(q alpha) regulates hexose uptake in C6 cells.
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PMID:Glucose uptake by C6 glioma cells is mediated by G(q alpha). 959 59

The ratio of GLUT1 mRNA to actin mRNA in brain was 6- to 13- fold greater than the corresponding ratio in spleen, lung, testis, heart, and skeletal muscle in the rat. However, the ratio of GLUT1 transcription rate to actin transcription rate is comparable in brain and the five other organs. Organ extracts were fractionated into cytosol and polysomes, and ultraviolet light cross-linking studies were performed with these proteins and 32P-labeled GLUT1 mRNA containing the 3'-untranslated region (UTR) generated from transcription plasmids. The cytosol of brain, lung, spleen, C6 glioma cells in tissue culture, and freshly isolated bovine brain capillaries express a pair of 95 kDa and 74 kDa proteins, designated collectively as p88, and the polysome fraction of brain, testis, or C6 glioma cells express a 44-kDa protein, designated p44. In a middle cerebral artery occlusion model, brain cytosol p88 was up-regulated and p44 was down-regulated. These findings are consistent with the hypothesis that GLUT1 gene expression is subject to regulation at the post-transcriptional level.
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PMID:GLUT1 glucose transporter: differential gene transcription and mRNA binding to cytosolic and polysome proteins in brain and peripheral tissues. 968 31


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