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 mitogenic action of endothelins (ETs) 1 and 3 was studied on C6 rat glioma cells in serum-free culture conditions. In order to characterize the ET receptor subtype involved in this effect, BQ-123, and ETA receptor selective antagonist was used. Our results confirmed that both ET-1 and ET-3 are mitogenic peptides for C6 cells and demonstrated for the first time that the ETA receptor antagonist BQ-123 inhibits the proliferative effect of both ET-1 and ET-3 in this cellular system, providing evidence of an atypical ET receptor on C6 cells.
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PMID:BQ-123 inhibits both endothelin 1 and endothelin 3 mediated C6 rat glioma cell proliferation suggesting an atypical endothelin receptor. 813 46

Endothelin (ET) receptor-binding assays using [125I]ET-1 in C6-glioma cells and in Rat-1 and Swiss 3T3 fibroblasts indicated the presence of two binding sites, one of which binds agonists at the pM range and the other at the nM range. All three cell lines exhibited the same pharmacological profile for agonist binding (ET-1 congruent to sarafotoxin-b > ET-3), which suggests that the receptor is of the ETA type. Binding of ET-1 to the receptor resulted in activation of two phospholipases, phospholipase C (PLC) and phospholipase D (PLD). The activation of PLC or PLD by endothelin in the three cell lines was mediated by the high affinity binding site (nM range) and was not significantly affected by either extracellular or intracellular Ca2+. Measurement of PLD activation by ET-1 and/or phorbol 12-myristate 13-acetate (PMA), in the presence and absence of two potent inhibitors of protein kinase C (PKC), strongly suggests that activation of PLD by ET receptor in C6 glioma cells as well as in Rat-1 and Swiss 3T3 fibroblasts involves both PKC-dependent and PKC-independent mechanisms.
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PMID:Endothelin receptors stimulate both phospholipase C and phospholipase D activities in different cell lines. 847 17

The endothelin (ET) peptides have been identified in the CNS, but there is a paucity of information on their physiological roles. NG108-15 cells, a clonal strain of a neuroblastoma x glioma hybrid cell line, have been widely used in neurobiological research since they retain certain differentiated properties of the non-transformed parental cells. It is known that NG108-15 cells respond to the ET peptides, but only limited information is available on the characterization of the ET receptors that mediate these effects. The present study was designed to identify the type(s) of ET receptors on NG108-15 cells in a proliferative state by competitive binding assays using [125I]ET-1 as the radiolabelled ligand and the receptor-selective ligands. ET-1, ET-3, BQ-123, sarafatoxin-6-c and [Ala1,3,11,15]ET-1. The results suggested the presence of conventional ETA and ETB receptor subtypes, with ETA in excess over ETB. These findings were consistent with the results of Northern analysis in that mRNAs encoding the ETA and ETB receptor subtypes were identified in NG108-15 cells, with a preponderance of ETA to ETB. Of considerable interest was the observation of other ET-binding components with much higher affinities than the conventional receptors. It remains to be demonstrated if these particular binding components are functional and represent differ gene products or arise from association of the conventional ETA and ETB receptor subtypes with themselves or other structures, e.g. proteins or lipids, of CNS origin.
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PMID:Endothelin binding to NG108-15 cells: evidence for conventional ETA and ETB receptor subtypes and super-high affinity binding components. 899 27

The endothelin (ET) peptides, ET-1, ET-2, and ET-3, as well as the ETA and ETB receptor subtypes, are known to occur in brain, but there is a dearth of information on the metabolism of these peptides by the central nervous system (CNS). In this study we have investigated the kinetics of ET-1 binding to and dissociation from the hybrid neuroblastoma x glioma cell line, NG108-15, which is known to contain functional ET receptors, and metabolism of bound ET-1. [125I]ET-1 was incubated with cells for various periods of time up to 6 h, and the nature of the radioactivity in the cell medium and lysate was analyzed by reverse phase high performance liquid chromatography (HPLC). It was found that NG108-15 cells are capable of degrading [125I]ET-1 to [125I]Tyr and several fragments of intermediate hydrophobicity; however, a portion of the cell-associated [125I]ET-1 was protected from degradation for several hours.
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PMID:Metabolism of endothelin-1 by neuroblastoma x glioma hybrid (NG108-15) cells. 914 3

Endothelin-1 (ET-1) is a 21 amino acids peptide that exerts several biological activities through interaction with specific G-protein coupled receptors. Increased ET-1 expression is frequently associated with pathological situations involving alterations in glutamate levels. In the present study, a brief exposure to ET-1 was found to increase aspartate uptake in C6 glioma cells, which endogenously express the neuronal glutamate transporter EAAC1 (pEC50 of 9.89). The stimulatory effect of ET-1 mediated by ETA receptors corresponds to a 62% increase in the Vmax with no modification of the affinity for the substrate. While protein kinase C activity is known to participate in the regulation of EAAC1, the effect of ET-1 on the glutamate uptake was found to be independent of this kinase activation. In contrast, the inactivation of Go/i type G-protein dependent signaling with pertussis toxin was found to impair ET-1-mediated regulation of EAAC1. An examination of the cell surface expression of EAAC1 by protein biotinylation studies or by confocal analysis of immuno-fluorescence staining demonstrated that ET-1 stimulates EAAC1 translocation to the cell surface. Hence, the disruption of the cytoskeleton with cytochalasin D prevented ET-1-stimulated aspartate uptake. Together, the data presented in the current study suggest that ET-1 participates in the acute regulation of glutamate transport in glioma cells. Considering the documented role of glutamate excitotoxicity in the development of brain tumors, endothelinergic system constitutes a putative target for the pharmacological control of glutamate transmission at the vicinity of glioma cells.
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PMID:Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cells. 1573 30

The proliferative and antiapoptotic actions of endothelin (ET)-1 in cancer cells have been documented and ET receptor antagonists have been exploited as potential anticancer drugs. Glioblastoma cell lines express both ETA and ETB receptors and previous works have shown that ETB receptors are involved in the proliferation of different cancer cell types. In this study we have investigated the effects of two structurally unrelated ETB receptor antagonists, BQ788 and A192621, on cell survival, proliferation and apoptosis in 1321-N1, U87 and IPDDCA2 glioma cell lines. BQ788 and A192621 reduced glioma cells viability and proliferation assessed by BrdU incorporation and cell cycle analysis by flow cytometry, while in contrast the ETA receptor antagonist BQ123 had no effect on cell survival. TUNEL assay and immunocytochemical experiments showed that BQ788 and A192621 trigger apoptotic processes mainly via activation of the intrinsic mitochondrial pathway involving caspase-9 activation, AIF release and cytochrome c translocation. Furthermore, treatment with ETB antagonists downregulates ERK- and p38MAPK-dependent pathways but does not affect VEGF mRNA levels. Our findings support the hypothesis that ETB antagonists represent a new promising therapeutic strategy for the treatment of high grade gliomas.
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PMID:Endothelin B receptor antagonists block proliferation and induce apoptosis in glioma cells. 1993 93

Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor characterized by its rapid infiltration to surrounding tissues during the early stages. The fast spreading of GBM obscures the initiation of the tumor mass making the treatment outcome undesirable. Endothelin-1 is known as a secretory protein presented in various types of brain cells, which has been indicated as a factor for cancer pathology. The aim of the present study was to investigate the molecular mechanism of cell migration in GBM. We found that various malignant glioma cells expressed higher amounts of endothelin-1, ETA, and ETB receptors than nonmalignant human astrocytes. The application of endothelin-1 enhanced the migratory activity in human U251 glioma cells corresponding to increased expression of matrix metalloproteinase (MMP)-9 and MMP-13. The endothelin-1-induced cell migration was attenuated by MMP-9 and MMP-13 inhibitors and inhibitors of mitogen-activated protein (MAP) kinase and PI3 kinase/Akt. Furthermore, the elevated levels of phosphate c-Jun accumulation in the nucleus and activator protein-1 (AP-1)-DNA binding activity were also found in endothelin-1 treated glioma cells. In migration-prone sublines, cells with greater migration ability showed higher endothelin-1, ETB receptor, and MMP expressions. These results indicate that endothelin-1 activates MAP kinase and AP-1 signaling, resulting in enhanced MMP-9 and MMP-13 expressions and cell migration in GBM.
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PMID:Exogenous endothelin-1 induces cell migration and matrix metalloproteinase expression in U251 human glioblastoma multiforme. 2475 49