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)

Incubation with L-DOPA induced a rise in GSH level in cultures of fetal rat mesencephalon, mouse neuroblastoma (Neuro-2A), human neuroblastoma (SK-N-MC), pig kidney epithelial cells (LLC-PK1), and glia from newborn rat brain, but not C6 glioma cells or neuronal cultures (no glia) from the mesencephalon. The pure neuronal cultures were destroyed by incubation with L-DOPA; added ascorbic acid or superoxide dismutase protected the cells. Washout of L-DOPA after 48 h amplified the rise in GSH content in mixed cultures (neurons plus glia). Examination of structure-activity relationships for elevating GSH levels in responsive cell types revealed that autooxidizable compounds (alpha-methyl-DOPA, dopamine, apomorphine, catechol, and hydroquinone) behaved similarly to L-DOPA, whereas structural analogues that cannot undergo autooxidation (3-O-methyl-DOPA, tyrosine, 2,4-dihydroxyphenylalanine, and resorcinol) failed to elevate GSH levels. Therefore, up-regulation of GSH appears to be a response to a mild oxidative stress. When mixed mesencephalic cultures were exposed to a strong oxidant stress by incubation with tert-butyl hydroperoxide, a loss in viability was seen. Cultures pretreated with L-DOPA or hydroquinone were protected from loss of viability. However, when cultures were pretreated with both L-DOPA and ascorbate, which prevents the rise in GSH level, protection was lost, in accord with the failure to up-regulate GSH. These results show that the up-regulation of cellular GSH evoked by autooxidizable agents is associated with significant protection of cells. Glia play an essential role in the response of mesencephalic cell cultures. An ability to up-regulate GSH may serve a protective role in vivo.
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PMID:L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress. 859 19

NBXFO hybridoma cells produced both the membrane and secreted isoforms of macrophage colony-stimulating factor (M-CSF). Murine bone marrow cells stimulated by the secreted form of M-CSF (sM-CSF) became Mac1+, Mac2+, Mac3+, and F4/80+ macrophages that inhibited the growth of NBXFO cells, but not L1210 or P815 tumor cells. In cytotoxicity studies, M-CSF activated macrophages and freshly isolated macrophages killed NBXFO cells in the presence of polymyxin B, eliminating the possibility that contaminating lipopolysaccharide (LPS) was responsible for the delivery of the cytotoxic signal. Retroviral-mediated transfection of T9 glioma cells with the gene for the membrane isoform of M-CSF (mM-CSF), but not for the secreted isoform of M-CSF, transferred the ability of macrophages to kill these transfected T9 cells in a mM-CSF dose-dependent manner. Macrophage-mediated killing of the mM-CSF transfected clone was blocked by using a 100-fold excess of recombinant M-CSF. Catalase, superoxide dismutase, and the nitric oxide inhibitor, N-omega-nitro-arginine methyl ester (NAME), did not effect macrophage cytotoxicity against the mM-CSF transfectant T9 clones. T9 parental cells when cultured in the presence of an equal number of the mM-CSF transfectant cells were not killed, indicating specific target cell cytotoxicity by the macrophages. Electron microscopy showed that macrophages were capable of phagocytosizing mM-CSF bearing T9 tumor cells and NBXFO hybridoma cells; this suggested a possible mechanism of this cytotoxicity. This study indicates that mM-CSF provides the necessary binding and triggering molecules through which macrophages can initiate direct tumor cell cytotoxicity.
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PMID:Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor. 865 38

The effect of membrane permeable cAMP analogues on the expression of extracellular superoxide dismutase (EC-SOD) was studied in rat C6 glioma. EC-SOD is constitutively expressed but stimulation with cAMP analogues still increased the EC-SOD transcription and the secreted SOD activity. The potency to enhance EC-SOD expression is correlated with the ability of the cAMP analogue to induce cAMP-dependent differentiation in C6. The increase in EC-SOD mRNA and in secreted activity depended on the concentration of the cAMP analogues and on the cultivation time. Twenty-four hours after addition of 0.5 mM N6, O'2-dibutyryl cAMP (dbcAMP) or N6-monobutyryl cAMP (N6-mbcAMP) EC-SOD mRNA expression increased approximately twofold, while stimulation for 68 h with 0.5 mM N6-mbcAMP or 1 mM 8-Chloro cAMP (ClcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell three- and fivefold, respectively. O'2-monobutyryl cAMP (O'2-mbcAMP) did not affect EC-SOD synthesis. The enhancement in EC-SOD activity did not require activation of protein kinase A. ATP, TGF-beta, IFN-gamma, and LPS did not affect EC-SOD synthesis. The presented data point to a cAMP-dependent pathway for the enhanced expression of EC-SOD by glial cells in brain.
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PMID:Cyclic AMP-induced differentiation increases the synthesis of extracellular superoxide dismutase in rat C6 glioma. 888 98

In an attempt to understand the change of superoxide dismutase (SOD) in tumor cells by hypoxia and hypoxia-normoxia exposure, the present study performed an in vitro investigation using rat glioma cell line in culture. Hypoxia was induced by an incubation with nitrogen gas for 15 h followed the normoxia exposure with air for 30 min. Activity of SOD in cytosolic and particulate of cells was determined by the reduction of nitroblue tetrazolium. Changes of mRNA for Cu,Zn-SOD or Mn-SOD were also characterized using Northern blotting analysis. Hypoxic stress decreased the activity of SOD, both Cu,Zn-SOD and Mn-SOD, in glioma cells. Expression of mRNA for SOD was elevated by hypoxic stress and the increase of mRNA level for Cu,Zn-SOD was more marked than that for Mn-SOD. In response to hypoxia-normoxia exposure, an increase of activity with a lower mRNA level for Mn-SOD was observed in glioma cells. However, changes of Cu,Zn-SOD both the activity and the level of mRNA were not found in glioma cells by hypoxia-normoxia. The obtained results suggest that the SOD in glioma cells can be activated to compensate the damage from free radicals during hypoxic stress.
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PMID:Changes of superoxide dismutase (SOD) mRNA and activity in response to hypoxic stress in cultured Wistar rat glioma cells. 930

This study investigated: (1) the effect of Hp as a hyperthermic sensitizer on glioma cells; and (2) the possible mechanism of hyperthermic sensitization by Hp using an exogenous scavenger specific to a particular reactive oxygen species. Hp at nontoxic doses at 37 degrees C significantly enhanced thermal cell damage at 41.5 degrees C and above in a dose-dependent manner. Thermal cell damage enhancement by HP was effectively suppressed by the addition of beta-carotene, a singlet oxygen scavenger, or SOD, a superoxide scavenger, but not by the addition of mannitol or catalase. These results support the following hypothesis: The generation of superoxide is increased in cells treated with Hp in combination with hyperthermia. Thermal cell damage enhancement by Hp is probably mediated by singlet oxygen generated via superoxide in an alternative pathway different from that of photosensitization. Hp has potential as a hyperthermic sensitizer because of the following advantages: (1) its dose-dependent enhancement of thermal cell damage; and (2) the lack of toxicity at physiological temperature at doses of Hp required for hyperthermic sensitization of tumour cells.
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PMID:Hyperthermic sensitization by hematoporphyrin on glioma cells. 978 73

In order to evaluate the intracellular function of glia maturation factor (GMF), we overexpressed GMF in C6 rat glioma cells using two methods: stable transfection using the pcDNA3 plasmid, and transient transfection using replication-defective human adenovirus. With both methods, C6 cells transfected with GMF and overexpressing the protein exhibit a lower saturation density in culture compared to non-transfected or vector alone controls. Transfected cells also exhibit morphological differentiation as shown by the outgrowth of cell processes. When inoculated into nude mice, transfected cells are less tumorigenic than controls, and express the mature astrocytic marker glial fibrillary acidic protein. In tissue culture, transfected cells show a 3.5-fold increase in CuZn-dependent superoxide dismutase (CuZnSOD) activity. Western blot analysis reveals a 3.5-fold increase in CuZnSOD protein, suggesting an induction of the enzyme. In view of recent findings that reactive oxygen species (ROS) and the antioxidant enzymes are intricately involved in key physiologic processes such as proliferation, differentiation and apoptosis, the study raises the possibility that CuZnSOD may be a mediator of GMF function.
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PMID:Overexpression of glia maturation factor in C6 cells promotes differentiation and activates superoxide dismutase. 981 56

It has been documented that C6 glioma cells can be changed into normal glial cells when they were cultured in serum free medium. In the present study, the expressions of inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) were investigated. The mRNA level of iNOS was markedly increased by lipopolysaccharide (LPS) in cultured rat brain astrocytes (RBA-1) but not in C6 glioma cells. However, increase of mRNA for iNOS by LPS can be obtained in C6 glioma cells when they were cultured in serum free medium. The mRNA level of magnesium-SOD (Mn-SOD) was increased by LPS in both cells while the expression of constituted SOD (Cu,Zn-SOD) was not stimulated by LPS. Western blotting analysis indicating the amount of protein showed a similar change. After serum deprivation, the protein of iNOS or Mn-SOD was increased by LPS in C6 glioma cells in a way similar as that in RBA-1 cells. These results suggest that serum free conditioned C6 glioma cells were adapted to astroglial cell-like properties which may express more iNOS and Mn-SOD mRNA in the presence of LPS.
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PMID:Effect of serum in medium on the expression of inducible nitric oxide synthase and superoxide dismutases in cultured C6 glioma cells. 1008 21

Many inherited neurological diseases and cancers could potentially benefit from efficient targeted gene delivery to neurons of the central nervous system. The nontoxic fragment C (HC) of tetanus toxin retains the specific nerve cell binding and transport properties of tetanus holotoxin. The HC fragment has previously been used to promote the uptake of attached proteins such as horseradish peroxidase, beta-galactosidase and superoxide dismutase into neuronal cells in vitro and in vivo. We report the use of purified recombinant HC fragment produced in yeast and covalently bound to polylysine [poly(K)] to enable binding of DNA. We demonstrate that when used to transfect cells, this construct results in nonviral gene delivery and marker gene expression in vitro in N18 RE 105 cells (a neuroblastoma x glioma mouse/rat hybrid cell line) and F98 (a glioma cell line). Transfection was dependent on HC and was neuronal cell type specific. HC may prove a useful targeting ligand for future neuronal gene therapy.
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PMID:Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin. 1009 62

To our knowledge, there have been no previous reports regarding the immunohistochemistry and image cytometry to demonstrate elevated Copper/zinc superoxide dismutase (Cu/Zn SOD) expression and numbers of the clonal cells in human gliomas. In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks. Cu/Zn SOD positive tumor cells were shown in 8 of 13 glioblastomas (mean quantitative immunoreactivity SOD score; 1), 3 of 8 anaplastic gliomas (score; 0.6), and none of 9 low-grade gliomas. The differences in SOD score was not significant. In hypertetraploid glioblastomas, time to progression was shorter than for hypertetraploid of anaplastic gliomas, while SOD scores were not significantly different. The same relationship held for tetraploid specimens. Considering variables in combination, hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p < 0.05) (1-5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas. The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs. Those results were suggested that the high grade glioma with a single clone and low SOD activity were effective for radiotherapy associated with oxidative stress, and that the high grade gliomas with more than two clones and high SOD activity were very less effective for same therapy. Cu/Zn SOD activity and the degree of the clonality in human gliomas should be very important factors influencing a choice of oxidative cytotoxic treatment.
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PMID:Copper/zinc superoxide dismutase, nuclear DNA content, and progression in human gliomas. 1042 Oct 66

Chronic treatment of rats with acrylonitrile (ACN) resulted in a dose-related increase in glial cell tumors (astrocytomas). While the exact mechanism(s) for ACN-induced carcinogenicity remains unresolved, non-genotoxic and possibly tumor promotion modes of action appear to be involved in the induction of glial tumors. Recent studies have shown that ACN induced oxidative stress selectively in rat brain in a dose-responsive manner. The present study examined the ability of ACN to induce oxidative stress in a rat glial cell line, a target tissue, and in cultured rat hepatocytes, a non-target tissue of ACN carcinogenicity. Glial cells and hepatocytes were treated for 1, 4 and 24 h with sublethal concentrations of ACN. ACN induced an increase in oxidative DNA damage, as evidenced by increased production of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in glial cells but not in rat hepatocytes. Hydroxyl radical formation following ACN treatment was also selectively increased in glial cells. Following 1 and 4 h of ACN exposure, the levels of the non-enzymatic antioxidant glutathione, as well as the activities of the enzymatic antioxidants catalase and superoxide dismutase were significantly decreased in the rat glial cells. Lipid peroxidation and the activity of glutathione peroxidase were not affected by ACN treatment in rat glial cells. No changes in any of these biomarkers of oxidative stress were observed in hepatocytes treated with ACN. These data indicate that ACN selectively induced oxidative stress in rat glial cells.
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PMID:Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile. 1042 6


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