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)

Effects of ginsenosides on nitric oxide (NO) production induced by lipopolysaccharide plus TNF-alpha (LNT) were examined in C6 rat glioma cells. Among several ginsenosides, ginsenoside Rd showed a complete inhibition against LNT-induced NO production. Ginsenoside Rd attenuated LNT-induced increased phosphorylation of ERK. Among several immediate early gene products, only Jun B and Fra-1 protein levels were increased by LNT, and ginsenoside Rd attenuated Jun B and Fra-1 protein levels induced by LNT. Furthermore, LNT increased AP-1 DNA binding activities, which were partially inhibited by ginsenoside Rd. Our results suggest that ginsenoside Rd exerts an inhibitory action against NO production via blocking phosphorylation of ERK, in turn, suppressing immediate early gene products such as Jun B and Fra-1 in C6 glioma cells.
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PMID:Effect of ginsenoside Rd on nitric oxide system induced by lipopolysaccharide plus TNF-alpha in C6 rat glioma cells. 1278 33

CD14 is a membrane-bound lipopolysaccharide receptor or, lacking the glycosylphosphatidylinositol anchor, is secreted to modulate cellular and humoral immune response by interacting directly with T and B cells. Because immunodepletion is thought to contribute to the grim prognosis of glioblastoma patients, we analyzed expression and release of CD14 in rat and human astrocytomas and glioma cell lines. Immunohistochemistry of 50 glioma biopsy specimens from low-grade diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV), and of the C6 rat glioma model demonstrated significantly more CD14-immunoreactive macrophages/microglial cells in glioblastomas than in less malignant gliomas. In WHO grade II and III astrocytomas, only perivascular cells showed immunoreactivity with CD14. In glioblastomas, CD14-immunoreactive cells were mainly found scattered throughout the entire tumor parenchyma. Double labeling experiments demonstrated CD14 immunoreactivity predominantly in CD68-expressing macrophages/microglial cells and some glioma cells. Western blotting, reverse transcription-PCR and consecutive sequencing confirmed expression and release of CD14 by four of six analyzed glioma cell lines. These results demonstrate that CD14 is expressed, and more importantly released, from a subset of human glioma cells and infiltrating macrophages/microglial cells that may contribute to immunodepletion observed in these patients.
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PMID:Expression and release of CD14 in astrocytic brain tumors. 1283 48

The pathology of Parkinson's disease involves oxidative damage to dopaminergic neurons of the substantia nigra. Oxidation of the dopamine (DA) neurotransmitter itself may contribute to the generation of a reactive oxygen species (ROS) and subsequent neurodegeneration. Glia cells can either exacerbate injury or exert protective properties on local neurons in the brain. We investigate glial antioxidant enzyme systems relative to ROS generated during cytokine activation, monoamine oxidase (MAO) activity and autoxidation of DA in glioma cells. Rat C6 glioma cells stimulated with lipopolysaccharide Escherichia coli 0111:B4 and interferon gamma (LPS/IFN-g) produced high levels of nitric oxide (241 nmol mg(-1) protein 24 h(-1)) but not superoxide (O(-) (2)) or hydrogen peroxide (H(2)O(2)). Basal C6 cells exhibited a rapid and robust capacity to remove exogenous H(2)O(2) within minutes. Preincubation with sodium azide but not buthionine-[S, R]-sulfoximine attenuated this response, indicating catalase as the primary enzyme responsible for this effect. The glioma catalase reaction rate was slightly attenuated by exposure to LPS/IFN-g for 24 h. However, the reduction in catalase activity was not due to nitric oxide, because both the supernatant and sodium nitroprusside had no effect on isolated catalase enzyme activity. Hydrogen peroxide was produced only through substrate-driven MAO activity in prepared lysate. However, the quantity of H(2)O(2) produced per unit time (0.46 nmol mg(-1) protein min(-1)) was negligible compared with the enormous capacity for its removal by catalase (213.9 nmol mg(-1) protein min(-1)) (> or =462 x greater). Similarly, H(2)O(2) generated by DA autoxidation per unit time (0.28 nmol mg(-1) protein equiv. min(-1)), was rapidly dissolved by glioma cells at high capacity (> or =750 x greater). In conclusion, C6 cells produce nitric oxide under cytokine/endotoxin-stimulated conditions. Moreover, C6 cells exhibit a dynamic H(2)O(2) scavenging capacity, with ample facility to dispose of the peroxide generated by both MAO activity and spontaneous DA autoxidation.
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PMID:Glioma cell antioxidant capacity relative to reactive oxygen species produced by dopamine. 1505 4

Adenosine is a potent inhibitor of inflammatory processes, and the A(2A) adenosine receptor (A(2A)AR) plays a key nonredundant role as a suppresser of inflammatory responses in vivo. In this study, we demonstrate that increasing A(2A)AR gene expression suppressed multiple inflammatory responses in both human umbilical vein endothelial cells (HUVECs) and rat C6 glioma cells in vitro. In particular, the induction of the adhesion molecule E-selectin by either tumor necrosis factor alpha (TNFalpha) or Escherichia coli lipopolysaccharide (LPS) was reduced by more than 70% in HUVECs, whereas inducible nitric-oxide synthase (iNOS) induction was abolished in C6 cells after exposure to interferon-gamma in combination with LPS and TNFalpha, suggesting that the receptor inhibited a common step in the induction of each of these pro-inflammatory genes. Consistent with this hypothesis, A(2A)AR expression inhibited the activation of NF-kappaB, a key transcription factor whose proper function was essential for optimal iNOS and E-selectin induction. However, although NF-kappaB binding to target DNA was severely compromised in both cell types, the mechanisms by which this occurred were distinct. In C6 cells, A(2A)AR expression blocked IkappaBalpha degradation by inhibiting stimulus-induced phosphorylation, whereas in HUVECs, A(2A)AR expression inhibited NF-kappaB translocation to the nucleus independently of any effect on IkappaBalpha degradation. Together, these observations suggest that A(2A)AR-mediated inhibition NF-kappaB activation is a critical aspect of its anti-inflammatory signaling properties and that the molecular basis of this inhibition varies in a cell type-specific manner.
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PMID:Specific inhibition of nuclear factor-kappaB-dependent inflammatory responses by cell type-specific mechanisms upon A2A adenosine receptor gene transfer. 1528 8

Both lead (Pb) and lipopolysaccharide (LPS) damage nervous system, partly, by the induction of tumor necrosis factor-alpha (TNF-alpha) in glia origin. In this study, we examined the Pb- and LPS-triggered signal leading to TNF-alpha expression in a glioma cell line, U-373MG. Both Pb and LPS increased the phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), which depended on the activation of MAPK kinase (MEK) and protein kinase C (PKC). Selective p42/44 MAPK inhibitor could reduce the Pb- and LPS-triggered TNF-alpha expression in U-373MG cells. Suppressing PKC by chelerythrine chloride completely diminished the Pb- and LPS-induced TNF-alpha expression in glial cells in the mouse brain. Thus, our results indicated that PKC-MEK-p42/44 MAPK is a common signaling pathway for Pb- and LPS-induced TNF-alpha expression in glial cells.
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PMID:Regulation of tumor necrosis factor-alpha in glioma cells by lead and lipopolysaccharide: involvement of common signaling pathway. 1530 94

We investigated the effect of gamma-mangostin purified from the fruit hull of the medicinal plant Garcinia mangostana on spontaneous prostaglandin E(2) (PGE(2)) genase release and inducible cyclooxy-2 (COX-2) gene expression in C6 rat glioma cells. An 18-h treatment with gamma-mangostin potently inhibited spontaneous PGE(2) release in a concentration-dependent manner with the IC(50) value of approximately 2 microM, without affecting the cell viability even at 30 microM. By immunoblotting and reverse-transcription polymerase chain reaction, we showed that gamma-mangostin concentration-dependently inhibited lipopolysaccharide (LPS)-induced expression of COX-2 protein and its mRNA, but not those of constitutive COX-1 cyclooxygenase. Because LPS is known to stimulate inhibitor kappaB (IkappaB) kinase (IKK)-mediated phosphorylation of IkappaB followed by its degradation, which in turn induces nuclear factor (NF)-kappaB nuclear translocation leading to transcriptional activation of COX-2 gene, the effect of gamma-mangostin on the IKK/IkappaB cascade controlling the NF-kappaB activation was examined. An in vitro IKK assay using IKK protein immunoprecipitated from C6 cell extract showed that this compound inhibited IKK activity in a concentration-dependent manner, with the IC(50) value of approximately 10 microM. Consistently gamma-mangostin was also observed to decrease the LPS-induced IkappaB degradation and phosphorylation in a concentration-dependent manner, as assayed by immunoblotting. Furthermore, luciferase reporter assays showed that gamma-mangostin reduced the LPS-inducible activation of NF-kappaB-and human COX-2 gene promoter region-dependent transcription. gamma-Mangostin also inhibited rat carrageenan-induced paw edema. These results suggest that gamma-mangostin directly inhibits IKK activity and thereby prevents COX-2 gene transcription, an NF-kappaB target gene, probably to decrease the inflammatory agent-stimulated PGE(2) production in vivo, and is a new useful lead compound for anti-inflammatory drug development.
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PMID:gamma-Mangostin inhibits inhibitor-kappaB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. 1532 59

Chloroquine, a well-known lysosomotropic agent, has long been used for the treatment of malaria and rheumatologic disorders. However, therapeutic doses of chloroquine are known to cause behavioral side effects. In the present study, we investigated whether chloroquine stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) synthesis in C6 glioma cells. Chloroquine caused dose-dependent increase in iNOS protein expression and NO production in C6 glioma cells. A tyrosine kinase inhibitor (genistein), a protein kinase C (PKC) inhibitor (Ro 31-8220), and a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB 203580) all respectively suppressed chloroquine-induced iNOS expression and NO release from C6 glioma cells. Chloroquine activates p38 MAPK and stimulates PKC-alpha and -delta translocation from the cytosol to the membrane in C6 glioma cells. Chloroquine-stimulated p38 MAPK activation was blocked by genistein (20 microM), Ro 31-8220 (3 microM), and SB 203580 (10 microM). Incubation of lipopolysaccharide (LPS)-stimulated cells with chloroquine at non-toxic concentrations (10-100 microM) for 48 h increased iNOS expression, and led to a significant loss of adherent cells. Induction of DNA fragmentation in floating cells indicated that the C6 glioma cells were undergoing apoptosis. Taken together, our data suggest that chloroquine may activate tyrosine kinase and/or PKC to induce p38 MAPK activation, which in turn induces iNOS expression and NO production.
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PMID:Chloroquine induces the expression of inducible nitric oxide synthase in C6 glioma cells. 1568 46

We studied the effects of Mao (Ephedrae herba) on lipopolysaccharide (LPS)-induced expression of inducible cyclooxygenase (COX-2) in C6 rat glioma cells. Western blot analysis showed that Mao inhibited LPS-induced expression of COX-2 protein, but not that of constitutive cyclooxygenase. Reporter gene assays showed that Mao reduced LPS-inducible NF-kappaB-dependent transcription that plays a crucial role in induction of COX-2 gene expression. This crude drug decreased LPS-induced IkappaBalpha degradation in a concentration-dependent manner without affecting LPS-induced IkappaB phosphorylation. These results suggest that Mao prevents LPS-induced NF-kappaB-dependent transcription by inhibiting IkappaB degradation and suppresses an increase in COX-2 protein expression in C6 cells.
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PMID:Ephedorae herba decreases lipopolysaccharide-induced cyclooxgenase-2 protein expression and NF-kappaB-dependent transcription in C6 rat glioma cells. 1600 36

In the course of our survey of natural compounds inhibiting prostaglandin E2 release and/or lipopolysaccharide (LPS)-induced transcriptional stimulation via NF-kappaB, a central regulator of inflammatory genes, from natural resources, we found garcinone B, a xanthone from callus tissue culture of Hypericum patulum, as a compound with such pharmacological activities, that is a derivative of gamma-mangostin which potently inhibits COX-1 and COX-2 activities to reduce PGE2 release from C6 rat glioma cells, and inhibits IKK activity to prevent NF-kappaB-dependent COX-2 gene transcription. Garcinone B, to a lesser extent, reduced A23187-induced increase in prostaglandin E2 release than gamma-mangostin and its structurally related compound, patulone, in C6 cells. This compound also prevented LPS-induced stimulation of NF-kappaB-dependent transcription. These results suggest that garcinone B becomes a unique pharmacological tool to investigate intracellular signaling pathways involved in inflammation.
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PMID:Garcinone B reduces prostaglandin E2 release and NF-kappaB-mediated transcription in C6 rat glioma cells. 1626 90

In an earlier study, we reported that nitric oxide is involved in lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate-induced malignant transformation via increases in metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression in rat glioma C6 cells, however the mechanism has remained undefined. Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate alone, induced transformation in glioma C6 cells (but not in human glioblastoma cells GBM-8401 cells) without affecting their viability. An increase in inducible nitric oxide synthase protein expression, nitric oxide production, and metalloproteinase 9 enzyme activity is identified lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-treated C6 cells, however lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate and 12-o-tetradecanoylphorbol 13-acetate (but not lipopolysaccharide) addition shows the similar inductive pattern on metalloproteinase 9 enzyme activity without affecting inducible nitric oxide synthase protein expression and nitric oxide production in GBM-8401 cells. Treatment of C6 cells with lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate increases the expression of phosphorylated extracellular regulated protein kinases and Jun N-terminal kinases, but not p38, proteins, and an addition of the extracellular regulated protein kinases inhibitor PD98059 or Jun N-terminal kinases inhibitors SP600125, but not the p38 inhibitor SB203580, significantly blocked lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced inducible nitric oxide synthase protein expression and metalloproteinase 9 enzyme activity accompanied by blocking morphological transformation in C6 cells. Among 19 structurally related flavonoids, kaempferol and wogonin exhibit significant inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced morphological transformation and colony formation, and attenuation of inducible nitric oxide synthase, phosphorylated extracellular regulated protein kinases protein expression, and metalloproteinase 9 enzyme activity was observed. 2'-OH flavone at a dose of 100 microM inhibition of lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events via apoptosis induction is identified. Furthermore, lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate, induces tumoral invasion and migration in vitro and in vivo, and those are blocked by kaempferol and wogonin addition. These data suggest that combination of lipopolysaccharide and 12-o-tetradecanoylphorbol 13-acetate promotes tumoral progression via activating metalloproteinase 9 enzyme activity and inducible nitric oxide synthase gene expression, which is located downstream of mitogen-activated protein kinases activation, in rat glioma cells C6. Kaempferol and wogonin exhibit effective inhibitory effects on lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced events, and thus possess the potential for further development.
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PMID:Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate induction of migration and invasion of glioma cells in vitro and in vivo: Differential inhibitory effects of flavonoids. 1658 Jul 79


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