UMLS:C0017638 - FACTA Search

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Query: UMLS:C0017638 (glioma)
30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of intracellularly generated H2O2 on cell viability, morphology, and biochemical markers of injury have been investigated in a clonal cell line of neuronal origin (140-3, mouse neuroblastoma X rat glioma) as a cell culture model for the role of oxidative stress in the long-term loss of neurons in the brain. The H2O2 was generated from the redox cycling of menadione, or by the oxidation of serotonin catalyzed by monoamine oxidase, to simulate the effect of amine neurotransmitter turnover. Incubation with menadione at concentrations as low as 10 microM for several hours resulted in significant losses of cell viability and altered morphology. Similar effects were evident in the presence of serotonin only after incubation overnight with concentrations > 1 mM. The cytotoxicity of either agent was potentiated by preincubation with specific inhibitors of two enzymes important to cellular antioxidant defenses, 3-amino-1,2,4-triazole for catalase and 1,3-bis(chloromethyl)-1-nitrosourea for glutathione reductase. Activity of another antioxidant enzyme of particular importance to antioxidant defenses in brain, the selenoprotein glutathione peroxidase, was stimulated fourfold by growth of cultures in the presence of sodium selenite as a source of active-site Se for the enzyme. The only effect of the selenite on other functionally coupled antioxidant enzymes was a decrease in activity of superoxide dismutase at concentrations > 200 nM. The selenite substantially protected cells against oxidative stress induced by combinations of menadione, 3-amino-1,2,4-triazole, and 1,3-bis(chloromethyl)-1-nitrosourea, but was only marginally effective with serotonin as a source of oxidative stress. The monoamine oxidase inhibitor pargyline increased cell survival in the presence of serotonin, demonstrating the role of this enzyme in its cytotoxicity. DNA damage (single strand breaks), but not lipid peroxidation, correlated with the cytotoxic effects of menadione.
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PMID:Oxidative stress in a clonal cell line of neuronal origin: effects of antioxidant enzyme modulation. 849 17

Erythrocyte antioxidant enzymes were analysed in 100 patients with intracranial neoplasm and in 47 controls. There was a significant decrease in RBC glutathione reductase (GRx) and superoxide dismutase (SOD) activity in most types of brain tumor cases. Patients with acoustic neurinoma showed a significant reduction in selenium-dependent glutathione peroxidase (Se-GPx) activity. A decrease in catalase (CT) activity was seen in most of the brain tumor patients but remained statistically insignificant when compared to controls. A significant increase in plasma ceruloplasmin concentration was observed in patients with glioma. These enzymes were also studied in 27 post-treatment cases. GRx activity returned to normal levels in these patients. RBC SOD and plasma ceruloplasmin levels showed a tendency to return to normal. Hence, a marked decrease in the antioxidant enzymes may have a role in the genesis of considerable oxidative stress in patients with brain tumors.
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PMID:Role of antioxidant enzymes in brain tumours. 1080 83

During aerobic metabolism, a small amount of partially reduced oxygen is produced, yielding reactive oxygen species (ROS). Peroxisomes and mitochondria are major contributors to cellular ROS production, which is normally balanced by consumption by antioxidants. The fatty acid analogue tetradecylthioacetic acid (TTA) promotes mitochondrial and peroxisomal proliferation, and may induce oxidative stress and change the growth potential of cancer cells. In the present study, we found that TTA reduced [(3)H]thymidine incorporation in the glioma cell lines BT4Cn (rat), D54Mg (human), and GaMg (human) in a dose- and time-dependent manner. The 50% inhibitory TTA doses were approximately 125 microM for BT4Cn and D54Mg cells and 40 microM for GaMg cells after 4 days. alpha-Tochopherol counteracted this inhibition in GaMg cells. TTA enhanced the oxidation of [1-(14)C]palmitic acid, which could be explained by stimulation of enzymes involved in peroxisomal (fatty acyl-CoA oxidase) and/or mitochondrial (carnitine palmitoyltransferase) fatty acid oxidation. The glutathione content and the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase were differentially affected. Increased malondialdehyde (MDA) production was seen in TTA-treated GaMg and D54Mg cells, but not in BT4Cn cells, in vitro. In BT4Cn tumor tissue from TTA-treated rats, MDA was increased while the alpha-tocopherol content tended to decrease. TTA increased the level of cytosolic cytochrome c in BT4Cn cells, which suggests induction of apoptotic cascades. Although several mechanisms are likely to be involved in the TTA-mediated effects on growth, we propose that modulation of cellular redox conditions caused by changes in fatty acid metabolism may be of vital importance.
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PMID:Growth reduction in glioma cells after treatment with tetradecylthioacetic acid: changes in fatty acid metabolism and oxidative status. 1126 48

Two substances which are products of the isoprenoid pathway, can participate in lipid peroxidation. One is digoxin, which by inhibiting membrane Na(+)-K+ ATPase, causes increase in intracellular Ca2+ and depletion of intracellular Mg2+, both effects contributing to increase in lipid peroxidation. Ubiquinone, another products of the pathway is a powerful membrane antioxidant and its deficiency can also result in defective electron transport and generation of reactive oxygen species. In view of this and also in the light of some preliminary reports on alteration in lipid peroxidation in neuropsychiatric disorders, a study was undertaken on the following aspects in some of these disorders (primary generalised epilepsy, schizophrenia, multiple sclerosis, Parkinson's disease and CNS glioma)--1) concentration of digoxin, ubiquinone, activity of HMG CoA reductase and RBC membrane Na(+)-K+ ATPase 2) activity of enzymes involved in free radical scavenging 3) parameters of lipid peroxidation and 4) antioxidant status. The result obtained indicates an increase in the concentration of digoxin and activity of HMG CoA reductase, decrease in ubiquinone levels and in the activity of membrane Na(+)-K+ ATPase. There is increased lipid peroxidation as evidenced from the increase in the concentration of MDA, conjugated dienes, hydroperoxides and NO with decreased antioxidant protection as indicated by decrease in ubiquinone, vit E and reduced glutathione in schizophrenia, Parkinson's disease and CNS glioma. The activity of enzymes involved in free radical scavenging like SOD, catalase, glutathione peroxidase and glutathione reductase is decreased in the above diseases. However, there is no evidence of any increase in lipid peroxidation in epilepsy or MS. The role of increased operation of the isoprenoid pathway as evidenced by alteration in the concentration of digoxin and ubiquinone in the generation of free radicals and protection against them in these disorders is discussed.
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PMID:Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders. 1127 6

The aim of the study was to evaluate the activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and superoxide dysmutase (SOD-1) in the single brain metastases. The activity of the GSH-Px was evaluated with the use of spectrophotometry, GSSG-R was evaluated basing on the method of Mize and Langdon and SOD-1 with Sykes et al. method. The examinations were carried out in 36 specimens (10 specimens of healthy brain tissue, 12 specimens of brain metastases, 14 specimens of glioma multiforme). The statistical analysis revealed significant increase (p < 0.001) of GSH-Px and GSSG-R activity within the single brain metastases in comparison with the healthy brain tissue.
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PMID:[Activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and superoxide dismutase (SOD-1) in single brain metastasis]. 1223 89

BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) is the mainstay in glioblastoma multiform chemotherapy with only minimal effects. BCNU may kill tumor cells via carbamoylating cytotoxicity, which irreversibly inhibits glutathione reductase with resultant accumulation of oxidized form of glutathione causing oxidative stress. S-nitrosoglutathione (GSNO) is a product of glutathione and nitric oxide interaction. We report that GSNO formation may underlie carbamoylating chemoresistance mediated by activation of inducible nitric oxide synthase. Transactivation of hypoxia-inducible factor-1 (HIF-1)-responsive genes reduces oxidative stress caused by glutathione depletion. We also noted that preconditioning of C6 glioma cells to induce HIF-1 and its downstream genes confers chemoresistance against carbamoylating cytotoxicity of BCNU.
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PMID:S-nitrosoglutathione and hypoxia-inducible factor-1 confer chemoresistance against carbamoylating cytotoxicity of BCNU in rat C6 glioma cells. 1596 67

Different cell types response differently to toxic insult. In a previous study, it was demonstrated that the C6 glioma cell is more sensitive to Cd induced oxidative stress than the HepG2 cells. To explain the difference between the two cell lines in their response to oxidative stress, it was hypothesized that the activity of glutathione metabolizing enzymes may be different. The objective of this study is to determine the activities of glutathione peroxidase (GPx) and glutathione reductase (GR) in the two cell lines and to explain how these differences may affect the susceptibility of the two cells to oxidative stress. In the HepG2 cells, the activity of GPx was 2.24+/-0.18 micromol/mg protein/min and that for GR was 5.63+/-0.58 micromol/mg protein/min. For the C6 glioma cells, GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11 micromol/mg protein/min, respectively. Using the kinetic equilibrium: K(eq)=([GSSG]x[NADPH]x[H(+)])/([GSH](2)x[NADP(+)]), and the GSH/GSSG previously published (HepG2: 2.6 and C6 glioma: 3.6), resting NADPH/NADP(+) for the cell lines were calculated. The results showed that NADPH/NADP(+) for HepG2 cells (17.8) is higher than that in the C6 glioma cells (10.8). These data supported the notion that the reducing power (NADPH/NADP(+)) in the HepG2 cells is higher than that in the C6 glioma cell and thus, the later would be more susceptible to oxidative stress. The results also suggested that besides GSH/GSSG, the activities of GPx and GR are important in predicting tissue redox state. Applying this hypothesis to animal tissues, the ratio of the activities of the two enzymes in mouse liver, cerebral cortex, hippocampus and cerebellum were measured. It was demonstrated that the activities of GPx and GR were different in the different tissues studied. The possible correlation between enzymatic activities and the redox state in the different tissues were discussed.
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PMID:Glutathione peroxidase and glutathione reductase activities are partially responsible for determining the susceptibility of cells to oxidative stress. 1688 53

Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.
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PMID:The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. 1690 7

Glioblastomas are notorious for their resistance to ionizing radiation and chemotherapy. We hypothesize that this resistance to ionizing radiation is due, in part, to alterations in antioxidant enzymes. Here, we show that rat and human glioma cells overexpress the antioxidant enzyme peroxiredoxin II (Prx II). Glioma cells in which Prx II is decreased using shRNA exhibit increased hyperoxidation of the remaining cellular Prxs, suggesting that the redox environment is more oxidizing. Of interest, decreasing Prx II does not alter other antioxidant enzymes (i.e., catalase, GPx, Prx I, Prx III, CuZnSOD, and MnSOD). Analysis of the redox environment revealed that decreasing Prx II increased intracellular reactive oxygen species in 36B10 cells; extracellular levels of H(2)O(2) were also increased in both C6 and 36B10 cells. Treatment with H(2)O(2) led to a further elevation in intracellular reactive oxygen species in cells where Prx II was decreased. Decreasing Prx II expression in glioma cells also reduced clonogenic cell survival following exposure to ionizing radiation and H(2)O(2). Furthermore, lowering Prx II expression decreased intracellular glutathione and resulted in a significant decline in glutathione reductase activity, suggesting a possible mechanism for the observed increased sensitivity to oxidative insults. Additionally, decreasing Prx II expression increased cell cycle doubling times, with fewer cells distributed to S phase in C6 glioma cells and more cells redistributed to the most radiosensitive phase of the cell cycle, G2/M, in 36B10 glioma cells. These findings support the hypothesis that inhibiting Prx II sensitizes glioma cells to oxidative stress, presenting Prxs as potential therapeutic targets.
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PMID:Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2). 1871 23

Our earlier studies have shown that simultaneous inhibition of glycolysis and pentose phosphate pathway using 2-deoxy-d-glucose (2-DG, an inhibitor of glycolysis) and 6-aminonicotinamide (6-AN, an inhibitor of pentose phosphate pathway) lead to metabolic oxidative stress (MOS), resulting in radiosensitization in malignant cells. Present study was carried out to investigate the effects of 2-DG and 6-AN on intricately regulated endogenous antioxidant defense against MOS during radiosensitization by this combination. Two human tumor cell lines {Head and Neck Squamous carcinoma (KB) and Glioma (BMG-1)} and one non-malignantly transformed cell line (human embryonic kidney, HEK) were used in this study. The presence of 2-DG and 6-AN (added just before irradiation) for 4h, significantly decreased the clonogenicity and metabolic viability of KB and BMG-1 cell lines, while no significant change was seen in HEK cells. Accumulation of ROS was observed only in malignant cell lines, which displayed a compromised redox status evident from enhanced NADP(+)/NADPH and GSSG/GSH ratios and a concomitant decrease in glutathione reductase level and activity at 24h following treatment. The levels and activities of Cu, Zn-SOD and Mn-SOD increased with MOS and were accompanied by a decreased GPx and unaltered catalase activity and level. These results suggest that non-coordinated expression of antioxidant defense, besides compromised redox status, led to selective radiosensitization in the malignant cells.
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PMID:Metabolic oxidative stress induced by a combination of 2-DG and 6-AN enhances radiation damage selectively in malignant cells via non-coordinated expression of antioxidant enzymes. 2036 70

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