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)

Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with opiate agonist resulted in loss of the acute opiate inhibition of adenylate cyclase activity with a concomitant increase in the enzymatic activity observable on addition of the antagonist naloxone. The role of membrane lipids in the cellular expression of these chronic opiate effects was investigated by the hydrolysis of phospholipids with various lipases. Treatment with phospholipase C from Clostridium welchii produced an enzyme concentration-dependent decrease of prostaglandin E1-stimulated adenylate cyclase activity in control or etorphine-treated (1 microM for 4 h) hybrid cells. In addition, incubation of hybrid cells with phospholipase C concentrations of greater than or equal to 0.5 U/ml completely abolished the compensatory increase in adenylate cyclase activity after chronic opiate treatment. This attenuation of the increase in adenylate cyclase activity by phospholipase C could be prevented by inclusion of phosphatidylcholine but not of phosphatidic acid during the enzymatic incubations. The specificity of the phospholipids involved in expression of the chronic opiate effect could be demonstrated further by the absence of effect exhibited by phospholipase C from Bacillus cereus and phospholipase D. Hydrolysis of the acyl side chains of phospholipids with phospholipase A2 did not alter the chronic opiate effect after removal of lysophosphatides with bovine serum albumin. Because the guanylylimidodiphosphate- and NaF-sensitive adenylate cyclase activities were not affected by these phospholipase treatments, the expression of the compensatory increase in adenylate cyclase activity is mediated via an increase in the coupling between hormonal receptor and adenylate cyclase with the participation of the polar head groups of the phospholipids and not the hydrophobic side chains.
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PMID:Effect of phospholipases on chronic opiate action in neuroblastoma X glioma NG108-15 hybrid cells. 301 58

The mechanism of action of the alkylating agent bis-(2-chloroethyl)sulfide (sulfur mustard, SM) was studied using the in vitro mouse neuroblastoma-rat glioma hybrid NG108-15 clonal cell line model. Following 0.3 mM SM exposure, cell viability remained high (> 80% of untreated control) up to 9 hr and then declined steadily to about 40% of control after 20-24 hr. During the early period of SM exposure, when there was no significant cell viability loss, the following effects were observed. The cellular glutathione level decreased 20% after 1 hr and 34% after 6 hr. Between 2 and 6 hr, there was a time-dependent increase (about 10 to 30%) in intracellular free calcium (Ca2+), which was localized to the limiting membrane of swollen endoplasmic reticula and mitochondria, to euchromatin areas of the nucleus, and to areas of the cytosol and plasma membrane. Moreover, there was also a time-dependent increase in the release of isotopically labeled arachidonic acid ([3H]AA) from cellular membranes. Increase in [3H]AA release was 28% at 3 hr and about 60-80% between 6 and 9 hr. This increase in [3H]AA release was inhibited by quinacrine (20 microM), which is a phospholipase (PLA2) inhibitor. At 16 hr after SM exposure, there was a large increase (about 200% of control) in [3H]AA release, which was coincident with a 50% loss of cell viability. These results suggest a Ca(2+)-mediated toxic mechanism of SM via PLA2 activation and arachidonate release.
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PMID:Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane. 787 77

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma x glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [IK(M) or "M-current"] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited IK(M) by 44% and 42%, respectively, at 100 microM. Mean IC50 values were: UTP, 0.77 +/- 0.27 microM; ATP, 1.81 +/- 0.82 microM. The order of nucleotide and nucleoside activity at 100 microM was: UTP = ATP > ATP [gamma S] = ITP > 2-MeSATP > ADP = GTP >> AMP-CPP, adenosine, where ATP[gamma S] is adenosine 5'-O-(3-thiotriphosphate), ITP is inosine 5'-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is alpha, beta methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 microM) or by pre-incubation for 12 h in 500 ng.ml-1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca(2+)-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
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PMID:Activation of nucleotide receptors inhibits M-type K current [IK(M)] in neuroblastoma x glioma hybrid cells. 789 8

Phospholipid topology in human brain tumor microsomes was investigated by the use of specific aminophospholipid tracer, trinitrobenzenesulfonic acid, and by phospholipase hydrolysis method. In non-neoplastic brain cortex and white matter the outer leaflet of the bilayer contains predominantly phosphatidylcholine and the inner leaflet mostly phosphatidylethanolamine and phosphatidylserine. Sphingomyelin is equally distributed between the two leaflets. In microsomes from glioma and meningioma tumors, a significant decrease in phosphatidylcholine and sphingomyelin at the outer surface was observed.
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PMID:Phospholipid asymmetry in microsomal membranes of human brain tumors. 817 54

It has been well established that patients with malignant glioblastomas exhibit T cell anergy. In this report, we further investigate the nature of this T cell anergy. The results demonstrate that tumor size but not location correlates with decreased mitogen or anti-CD3 mAb responsiveness of T cells obtained from patients. Stimulation of the TCR/CD3 complex on these patients' T cells revealed defects in early transmembrane signaling. Both PHA and anti-CD3 mAb activated PBL and T cells obtained from patients exhibited a marked decrease in the tyrosine phosphorylation of a number of proteins. In particular, decreased phosphorylation of pp100 and phospholipase Cgamma1 (PLCgamma1) was observed. In addition, PLCgamma1 and p56(lck) protein levels were dramatically reduced in T cells obtained from patients harboring a glioma. In contrast, the protein levels of p59(fyn) were normal or only slightly reduced in T cells obtained from patients with gliomas. Quantitation of free intracellular calcium concentrations ([Ca2+]i) after mitogen (PHA) stimulation or ionomycin treatment of T cells obtained from patients revealed that they mobilize less calcium than do T cells obtained from normal subjects. Stimulation of T cells obtained from patients with PMA and ionomycin, which should bypass the requirement for PLCgamma1 activation as well as directly activate the p21(ras) signaling pathway, did not restore the proliferative capacity of these T cells to normal levels. These results indicate that the anergy observed in T cells obtained from these patients is a consequence of one or more defects in the early transmembrane signaling events associated with TCR/CD3 stimulation.
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PMID:T cell receptor-mediated signaling is defective in T cells obtained from patients with primary intracranial tumors. 937 40

Scatter factor/hepatocyte growth factor (SF/HGF) and its tyrosine kinase receptor c-met are developmentally expressed, neuroprotective, and tumorigenic within the CNS. In the present study SF/HGF is shown to induce the expression of c-met in two human glioblastoma cell lines, U-373 MG and T98G, and the signaling pathways involved in this induction are dissected. SF/HGF activated mitogen-activated protein kinase (MAPK) and inhibition of either Ras or MAPK-kinase completely inhibited SF/HGF-mediated c-met induction. Inhibition of phospholipase-C (PLC) did not affect c-met induction in either cell line. Inhibition of phosphoinositide 3-kinase (PI3-kinase) substantially reduced c-met induction by SF/HGF in T98G cells but had no effect in U-373 MG cells. Protein kinase C (PKC) inhibition reduced c-met induction in T98G cells but not in U-373 MG cells. SF/HGF induced the expression of c-fos and c-jun mRNA and increased the levels of AP-1 transcription factor in both cells lines as determined by AP-1-luciferase reporter expression. Transfection of either cell line with TAM-67, a dominant negative for the jun transactivation domain, completely inhibited AP-1 and c-met induction by SF/HGF. These results support a model of c-met induction by SF/HGF in human glioma cells that uniformly involves Ras, MAPK, and AP-1 and additionally involves PI3-kinase and PKC in some cell lines.
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PMID:Signaling pathways in the induction of c-met receptor expression by its ligand scatter factor/hepatocyte growth factor in human glioblastoma. 1123 34

Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and beta-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from beta-NAD+. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cbeta and beta-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca2+ from the type II ryanodine receptors as well as to facilitate Ca2+ influx through voltage-dependent Ca2+ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G(q/11)-coupled receptors can control cADPR-dependent modulation in Ca2+ signaling.
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PMID:Signal transduction from bradykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase. 1125 66

Dextran-conjugated EGF (EGF-dextran) has a potential use for targeted radionuclide therapy of tumors that overexpress the epidermal growth factor receptor (EGFR). There are plans to treat both bladder carcinomas and malignant gliomas with local injections of radiolabeled EGF-dextran since these tumors often express high levels of EGFR. In this report we show that EGF and EGF-dextran differentially activate the EGFR. In the human glioma cell line U-343, activation of the serine/threonine kinases Erk and Akt is identical upon stimulation with EGF or EGF-dextran. However, the effect on phospholipase Cgamma1 (PLCgamma1) phosphorylation differs. In cells stimulated with EGF-dextran, the PLCgamma1 phosphorylation is lower than in cells stimulated with EGF. This observation could be explained by the fact that the PLCgamma1 association sites in the EGFR, tyrosine residues 992 and 1173, were phosphorylated to a lower degree when the receptor was stimulated with EGF-dextran as compared to with EGF.
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PMID:EGF and dextran-conjugated EGF induces differential phosphorylation of the EGF receptor. 1237 11

Platelet-derived growth factor (PDGF) is a growth factor family of ligands and receptors known to activate phosphatidylinositol 3-kinase, mitogen-activated protein kinase, Jak family kinase, Src family kinase, and phospholipase Cgamma signal transduction pathways, some of which have been causally linked to glioma formation. Extensive involvement of PDGF in development and its implication in a variety of pathologic conditions, including gliomagenesis, are mediated not only by autocrine effects but by paracrine effects. Many researchers view brain tumors as clonal entities derived from the cancer stem cell; however, recent documentation of the importance of the tumor microenvironment for glioma initiation and progression as well as the ability of neural stem or progenitor cells to migrate toward the sites of injury or tumor formation reveals additional complexities in brain tumorigenesis. Paracrine effects of PDGF in animal models of gliomagenesis, continued adult neurogenesis capable of increasing in response to brain injury, and the growth factor-rich environment of brain tumors suggest that recruitment may play a role in gliomagenesis. In this view, glioma formation involves recruitment of cells from the adjacent brain and possibly other sites.
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PMID:Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment. 1724 53

Given our previous findings that human cytomegalovirus (HCMV) nucleic acids and proteins are expressed in human malignant glioma in vivo, we investigated cellular signaling events associated with HCMV infection of human glioma and astroglial cells. HCMV infection caused rapid activation of the phosphatidylinositol-3 kinase (PI-3K) effector AKT kinase in human astro-glial and fibroblast cells, and induced tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Co-immunoprecipitation experiments revealed association of the p85 regulatory subunit of PI-3K with a high-molecular weight protein phosphorylated on tyrosine, following short-term exposure to HCMV. In contrast to a previous report, we were unable to confirm the identity of this high-molecular weight protein as being the epidermal growth factor receptor (EGFR). Stimulation of glioma and fibroblast cell lines over-expressing EGFR with HCMV (whole virus) or soluble glycoprotein B did not induce tyrosine phosphorylation of the receptor, as did the genuine ligand, EGF. Furthermore, we found that expression levels of the human ErbB1-4 receptors were not rate-limiting for HCMV infection. Dispensability of EGFR function during early HCMV infection was substantiated by demonstration of viral immediate early gene expression in cells lacking the EGFR gene, indicating that HCMV may promote oncogenic signaling pathways independently of EGFR activation. Among non-receptor cellular kinases, HCMV infection induced phosphorylation of focal adhesion kinase (FAK) Tyr397, which is indispensable for integrin-mediated cell migration and invasion. HCMV-induced FAK activation was paralleled by increased extracellular matrix-dependent migration of human malignant glioma but not normal astro-glial cells, suggesting that HCMV can selectively augment glioma cell invasiveness.
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PMID:Human cytomegalovirus induces cellular tyrosine kinase signaling and promotes glioma cell invasiveness. 1758 4


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