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)

C6 glioma cells, and primary cultures of mouse astrocytes, stimulated with lipopolysaccharide (LPS) release an interleukin-1 like factor (IL-1) which enhances lectin-induced T-lymphocyte proliferation and promotes the release of interleukin-2 (IL-2) by ConA-stimulated thymocytes. In the present study, the glia maturation factor (GMF) was found not only to induce differentiation of glioblasts, but also to elicit the secretion of IL-1 like factors by cultured mouse astrocytes and their precursor cells. GMF was also effective in triggering IL-1 release by macrophages. Contamination of the 23 000 MW GMF preparation with LPS was excluded by the Limulus lysate assay and by using C3H/HeJ LPS-nonresponder mice whose glia and macrophages responded to GMF but not to LPS, by IL-1 release. Through its ability to induce glial differentiation and IL-1 release, GMF may represent an important endogenous signal, triggering both reactive gliosis and the development of an immune response within the central nervous system.
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PMID:Dual effect of glia maturation factor on astrocytes. Differentiation and release of interleukin-1 like factors. 660 46

Known and unknown host factors determine the individual susceptibility to carcinogenic agents. Such factors may interact with either the phase of transformation (initiation) or with the phase of proliferation (promotion). Some of these factors have been recognized as potential determinants of the degree of susceptibility or resistance to cancer. Transformation may be impeded by a low rate of absorption of carcinogenic agents (barrier effect), by the availability of deactivating enzymes operative at several steps of the metabolism of carcinogenic agents, and by a high repair capability of DNA damage. Proliferation of transformed cells may be impeded or prevented by immune defense mechanisms and by maturation factors such as nerve growth factor (NGF), glia maturation factor, fibroblast growth factor, and others. NGF has already been shown to be capable of maturing anaplastic glioma cells (clone F98) and reducing their rate of growth. Rats treated with NGF following implantation of anaplastic glioma cells had a significantly decreased tumor growth rate and increased survival time. NGF administration to pregnant rats preceding exposure to ethylnitrosourea (ENU) (50 mg/kg, 21st day of gestation) or to offspring transplacentally exposed to ENU resulted in reduction of neurinoma development. The importance of NGF as a suppressing agent of neoplastic proliferation and as a prospective tumor therapeutic needs further exploration.
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PMID:Potential factors in carcinogenesis and tumor regression. 685 28

The effect of bovine glia maturation factor on the growth pattern of cancer cells was investigated in the rat glioma cell line 354A. When the cells were grown in the serum-free defined medium N2 in the absence of the factor, the cells proliferated with a doubling time of 24 hr without showing contact inhibition. After reaching confluency, the cell layer formed numerous foci from which heaps of cell colonies arose. The addition of glia maturation factor to the culture stimulated cell division in the logarithmic phase but prevented overgrowth once the cells arrived at confluency. The ability of glia maturation factor to restore contact inhibition suggests a regulatory role in normal and neoplastic cells.
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PMID:Glia maturation factor promotes contact inhibition in cancer cells. 694 89

Optimal bioassay conditions for bovine glia maturation factor (GMF) were determined among glial cells from normal glioblasts to glioma cells. Rat glioblasts 4-8 days after subculture show the highest response t GMF with regard to morphological transformation and mitogenic activity. Bovine GMF enhances DNA synthesis of rat glioblasts at 12 h after stimulation; maximum incorporation of [methyl-3H]thymidine was detected at 18 h. GMF increases twofold the saturation density of rat glioblasts but does not alter that of C6 astrocytoma cells. The apparent inhibition of mitogenic activity of high doses of GMF is seen in both normal and malignant glial cells.
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PMID:Biological effects of bovine glia maturation factor on glial cells in culture. 726 48

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

Human glia maturation factor-gamma (hGMF-gamma) is a recently identified gene that may be involved in glial differentiation, neural regeneration, and inhibition of tumor cell proliferation. The gene maps to the long arm of chromosome 19 at band q13.2, a region that is frequently deleted in human malignant gliomas and is thus suspected to harbor a glioma tumor suppressor gene. Given the putative role of hGMF-gamma in cell differentiation and proliferation and its localization to chromosome 19q13, this gene is an interesting candidate for the chromosome 19q glioma tumor suppressor gene. To evaluate this possibility, we determined the genomic structure of human hGMF-gamma and performed mutation screening in a series of 41 gliomas with and without allelic loss of chromosome 19q. Mutations were not detected, which suggests that hGMF-gamma is not the chromosome 19q glioma suppressor gene. However, the elucidation of the genomic structure of hGMF-gamma may prove useful in future investigations of hGMF-gamma in the normal adult and developing human nervous system.
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PMID:The human glia maturation factor-gamma gene: genomic structure and mutation analysis in gliomas with chromosome 19q loss. 1054 89

The 17-kDa endogenous brain protein glia maturation factor (GMF) was transfected into C6 rat glioma cells using a replication-defective human adenovirus vector. The cells overexpressed GMF but did not secrete the protein into the medium. Transfection with GMF led to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB), as evidenced by electrophoretic mobility shift assay of the nuclear extract, using a double-stranded oligonucleotide probe containing the consensus binding sequence for NF-kappaB. The specificity of binding was demonstrated by competition with unlabeled probe and by the nonbinding of the mutant probe. Binding was detectable as early as 3 h after transfection, peaked at 6 and 12 h, and gradually declined thereafter. The observed NF-kappaB activation was reduced by cotransfection with catalase and by the presence of high concentrations of pyruvate in the medium, suggesting the involvement of H2O2. The p38 mitogen-activated protein kinase inhibitor SB-203580 also suppressed the GMF-activated NF-kappaB, suggesting the involvement of the p38 signal transduction cascade. On the other hand, the phorbol ester phorbol 12-myristate 13-acetate activated NF-kappaB whether or not GMF was overexpressed. Along with NF-kappaB activation was an enhanced expression of superoxide dismutase (SOD), which was suppressed if NF-kappaB nuclear translocation was blocked by its specific decoy DNA, implicating NF-kappaB as an upstream mediator of this antioxidant enzyme. The p38 inhibitor SB-203580 also blocked the GMF-activated SOD. As NF-kappaB and SOD are both pro-survival signals, the results suggest a cytoprotective role for endogenous GMF in glial cells.
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PMID:Activation of nuclear factor-kappaB in C6 rat glioma cells after transfection with glia maturation factor. 1064 10

Glial cells play active roles in neuronal survival, as well as neuroprotection against toxic insult. Recent studies suggest that the brain protein glia maturation factor (GMF) is involved in intracellular signaling in glia. This study investigated whether or not GMF plays a role in the survival-promoting and neuroprotective functions of glia. C6 glioma cells were transfected in vitro with GMF utilizing an adenovirus vector. The transfected cells overexpressed GMF intracellularly, but did not secrete the protein. The conditioned medium (CM) was obtained from the GMF-transfected cells (CM-GMF) and tested on primary neuronal cultures, consisting of cerebellar granule cells (CGC). The CGC cultures were utilized because these cultures have a background level of cell death, and the survival-promoting, i.e. neurotrophic effect, of the CM could be tested. In addition, since CGC cultures are ethanol-sensitive (ethanol enhances neuronal death), the neuroprotective effect of the CM against ethanol-induced cell death was tested also. We demonstrated that the CM-GMF had an enhanced neurotrophic effect as well as an increased neuroprotective effect against ethanol-induced cell death compared to control CM obtained from untransfected C6 cells (CM-Mock) or CM obtained from cells transfected with an unrelated gene (CM-LacZ). Because neurotrophins have trophic and protective effects, we investigated whether GMF-transfection upregulated the expression of neurotrophins in C6 cells. RT-PCR verified that GMF-transfected C6 cells had increased mRNA levels for BDNF and NGF. Immunoblotting corroborated the RT-PCR results and indicated that CM-GMF contained greater concentrations of BDNF and NGF protein compared to CM-Mock and CM-LacZ. A soluble TrkB-IgG fusion protein, which selectively binds BDNF and prevents its binding to the neuronal TrkB receptor, eliminated the neurotrophic effect of CM-GMF; whereas anti-NGF antibody was ineffective in preventing this effect, suggesting that the neurotrophic effect was due to BDNF. On the other hand, both the TrkB-IgG fusion protein and anti-NGF reduced neuroprotection, suggesting that BDNF and NGF both contribute to the neuroprotective effect of CM-GMF. In conclusion, GMF upregulates the expression of BDNF and NGF in C6 cells, and these factors exert neurotrophic and neuroprotective functions on primary neurons.
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PMID:Transfection of C6 glioma cells with glia maturation factor upregulates brain-derived neurotrophic factor and nerve growth factor: trophic effects and protection against ethanol toxicity in cerebellar granule cells. 1081 33

It is standard practice, whenever a researcher finds a new gene, to search databases for genes that have a similar sequence. It is not standard practice, whenever a researcher finds a new gene, to search for genes that have similar expression (co-expression). Failure to perform co-expression searches has lead to incorrect conclusions about the likely function of new genes, and has lead to wasted laboratory attempts to confirm functions incorrectly predicted. We present here the example of Glia Maturation Factor gamma (GMF-gamma). Despite its name, it has not been shown to participate in glia maturation. It is a gene of unknown function that is similar in sequence to GMF-beta. The sequence homology and chromosomal location led to an unsuccessful search for GMF-gamma mutations in glioma. We examined GMF-gamma expression in 1432 human cDNA libraries. Highest expression occurs in phagocytic, antigen-presenting and other hematopoietic cells. We found GMF-gamma mRNA in almost every tissue examined, with expression in nervous tissue no higher than in any other tissue. Our evidence indicates that GMF-gamma participates in phagocytosis in antigen presenting cells. Searches for genes with similar sequences should be supplemented with searches for genes with similar expression to avoid incorrect predictions.
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PMID:Gene expression versus sequence for predicting function: Glia Maturation Factor gamma is not a glia maturation factor. 1562 33

Growth-promoting factors in the extracts of various glioma cell lines (C6, LRM55 and 354A) were investigated. The cell extracts of astrocytoma (C6) and mixed glioma (LRM55) showed a high mitogenic activity to normal glioblasts. With its low content of intracellular growth-promoting factor, rat peripheral glioma (354A) exhibited a high proliferative response to C6 cell extracts. The factor which was partially purified from C6 solid tumor by ion exchange and gel filtration column chromatographies had two forms of different molecular weights (150,000 Mr and 35,000 Mr) and the low molecular weight form was further split into two acidic proteins (pl 5.0 and pl 6.0) by isoelectric focusing. The mitogenic activity of the factor was susceptible to heat and to proteases, and the factor showed no esteropeptidase activity. These physicochemical properties closely resemble those of glia maturation factor from porcine brains.
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PMID:Identification of growth-promoting factors from various glioma cell lines and partial purification of the factor from C6 solid tumor. 2048 89


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