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)

Immunohistochemically we investigated Rosenthal fibers (RFs) on specimen surgically removed from patients with glioma (three cerebellar astrocytomas, three optic gliomas, two spinal cord astrocytomas, one spinal ganglioglioma). Pathological diagnoses were pilocytic astrocytoma, fibrillary astrocytoma, and ganglioglioma. We utilized sections from the formalin-fixed paraffin-embedded tissues and stained them with H & E, PTAH, PAS as well as with anti-GFAP (glial fibrillary acidic protein) antibody (Ab) and two anti-ubiquitin Abs...anti-PHF (paired helical filament) monoclonal Ab (DF2) which recognizes ubiquitin (H. Mori in Science) and anti-ubiquitin polyclonal Ab provided by Dr. Haas. The primary antibodies were diluted with Tris-saline as follows: anti-GFAP (1:500), DF2 (culture medium without dilution), anti-ubiquitin (2 micrograms/ml). Sections were deparaffinized and incubated with primary antibodies overnight at room temperature. They were visualized by the avidin-biotin-peroxidase complex (ABC) procedure (Vectastain, Vector, USA) and counterstained with hematoxylin. Negative control sections were treated by omitting the primary antibodies. In the representative specimen we compared H & E, anti-GFAP and anti-ubiquitin staining on 3 microcrons serial sections. RFs were eosinophilic (bright red on H & E), purply-stained with PTAH (metachromasia), black with Heidemhein's iron-hematoxylin, and negative with PAS. Anti-GFAP Ab stained glial filaments diffusely in the cytoplasm and cell process of astrocytomas in every case. The peripheral parts of most RFs were intensely stained with anti-GFAP. The whole part of some RFs showed dark staining, and no part of a few RFs showed positive reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical study on Rosenthal fibers in gliomas using anti-GFAP and anti-ubiquitin antibodies]. 169 68

Chromatin condensation during apoptosis induced by TGF beta 1 in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells was examined and compared with that occurring during mitosis. Apoptotic (round-up) cells were selectively detached from the culture surface by a mechanical shock. Their histones were analysed in comparison with those obtained from TGF beta 1-treated cells remaining attached to the culture surface, from control cells not treated with TGF beta 1 and from metaphase cells. While mitosis-specific hyperphosphorylation of histones H1 and phosphorylation of histone H3 was not observed in apoptotic cells, apoptotic chromatin lacked ubiquitinated histone H2A (histone uH2A) as did metaphase chromosomes. The cellular level of free ubiquitin and the overall pattern of ubiquitin-conjugated proteins were, however, found to remain unaltered in apoptotic cells, suggesting that the ubiquitin conjugating machinery for histone H2A may be specifically perturbed during the chromatin condensation occurring in apoptosis.
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PMID:Disappearance of ubiquitinated histone H2A during chromatin condensation in TGF beta 1-induced apoptosis. 776 93

Glucose stimulates expression of the insulin-like growth factor I (IGF-I) gene in cultured C6 glioma cells. This stimulation is specific, as the expression of other genes, including those encoding hypoxanthine guanine phosphoribosyl transferase (HPRT) and ubiquitin, is not similarly affected by glucose. IGF-I gene expression is also stimulated by lactate, suggesting that the stimulatory effect is mediated by a product of glycolysis. Additional results indicate that the abundance of IGF-I mRNA is considerably higher in stationary confluent cells than in log-phase growing cells. This regulation is also specific for IGF-I, as HPRT mRNA is regulated in the opposite direction.
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PMID:Glucose stimulates IGF-I gene expression in C6 glioma cells. 782 54

In this report we describe a glioblastoma multiforme with focal granular cell change. In most astroglial tumors with granular cells, the granular appearance is due to the presence of periodic acid-Schiff-positive, membrane-bound cellular debris. In the present case the granular appearance was due to the presence of many small Rosenthal fibers, which were immunoreactive for glial fibrillary acidic protein, vimentin, ubiquitin, and heat-shock protein 27, but not for alpha-B crystallin. The ultrastructural characteristics are described. These findings demonstrate that granulofilamentous inclusions with the appearance of Rosenthal fibers in glial tumors are a structurally heterogeneous feature.
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PMID:Rosenthal fibers producing a granular cell appearance in a glioblastoma. 839 34

The cyclopentenone PGs (PGA and PGJ series) inhibit tumor cell proliferation in vitro and tumorigenesis in vivo via mechanisms that are at present poorly understood. The C6 rat glioma cell line synthesizes and secretes insulin-like growth factor-I (IGF-I), which is believed to act as an autocrine factor for these cells. PGA2 inhibits the proliferation of the C6 cells and causes an increase in the fraction of cells in the G1 phase of the cell cycle. The inhibition of cell proliferation by PGA2 is accompanied by a decrease in the abundance of IGF-I messenger RNA (mRNA). This regulation of IGF-I gene expression is specific, as the abundance of hypoxanthine-guanine phosphoribosyl transferase (HPRT) and ubiquitin mRNA is not significantly affected by PGA2. The repression of IGF-I gene expression is observed at PGA2 concentrations as low as 10 microM and is evident within 4 h after treatment of the C6 cells with PGA2. In addition to specifically regulating the expression of the IGF-I gene, PGA2 also decreases the abundance of cyclin D1 mRNA and increases the abundance of Waf1 mRNA. The inhibition of cell proliferation by PGA2 is partially reversed by coaddition of IGF-I, indicating partial dominance of IGF-I action over PGA2 action. To investigate the molecular basis for the regulation of IGF-I gene expression by PGA2, we developed a sensitive RT-PCR assay for IGF-I nuclear transcripts. A similar assay was developed for quantifying HPRT transcripts, which were used as a control. Treatment of the C6 cells with 20 microM PGA2 resulted in approximately a 6-fold decrease in IGF-I mRNA and IGF-I nuclear transcripts. In contrast, HPRT mRNA and nuclear transcript levels were not significantly affected by PGA2. These results indicate that the decrease in IGF-I mRNA abundance that occurs in response to PGA2 is caused largely by a decrease in IGF-I nuclear transcript levels. To identify the cis-acting element that mediates the effect of PGA2 on IGF-I transcription, C6 cells were transiently transfected with IGF-I/luciferase expression constructs in which luciferase transcription is driven by IGF-I P1 promoter fragments extending from -1711 to -328 or from -1114 to +328 relative to the beginning of exon 1. Treatment of cells with PGA2 in these transient transfection assays did not decrease luciferase activity. These results suggest that the cis-acting regulatory element required for the response to PGA2 is located outside the -1711 to +328 promoter interval.
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PMID:Prostaglandin A2 specifically represses insulin-like growth factor-I gene expression in C6 rat glioma cells. 904 99

Several epidemiological studies suggest the involvement of aluminum (Al) in the pathogenesis of Alzheimer's disease (AD). There is an increase in the levels of Abeta and ubiquitin in the pathological lesions of AD. Therefore, we have investigated whether aluminum (Al) treatment alters the levels of Abeta and ubiquitin in murine neuroblastoma (NBP2) and rat glioma (C-6) cell cultures. At a low concentration (10 microM), aluminum sulfate stimulated the level of immunoreactive Abeta and ubiquitin in NBP2 cells without changing the levels of the amyloid precursor protein (APP). However, at higher concentrations (100 and 500 microM), aluminum failed to elicit any significant effect on beta-amyloid, whereas ubiquitin levels continued to increase. No changes in the Abeta and ubiquitin content were found in the C-6 glioma cells following treatment with Al at any of the concentrations tested. Exposure of cells to aluminum salts did not alter the rate of proliferation in either of the two cell lines. These data suggest that one of the mechanisms by which Al may play a role in AD is by promoting the formation of Abeta and ubiquitin in neurons.
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PMID:Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells. 1072 Oct 10

Proteasome inhibitors were shown previously to induce mitochondria-independent and caspase-3-dependent apoptosis in human glioma cell lines by unknown mechanisms. Here, we showed that treatment with proteasome inhibitors, lactacystin or acetyl-leucinyl-leucinyl-norleucinal, led to elevation of the steady-state c-Myc protein but not c-myc mRNA, suggesting the accumulation of c-Myc protein by proteasome inhibitors. In addition, the marked association of c-Myc protein with ubiquitin by treatment with proteasome inhibitors indicated the involvement of proteasome in c-Myc proteolysis and the stabilization of c-Myc protein by proteasome inhibitors in vivo. The expression of Fas (also termed CD95 or APO-1) mRNA, if analyzed by reverse transcriptase polymerase chain reaction assay, was found to occur constitutively, and increased slightly by the treatment with proteasome inhibitors. In contrast, the expression of Fas ligand (FasL) mRNA was markedly induced temporarily before the activation of caspase-3 by the treatment. Agonistic anti-Fas antibody (CH11) induced apoptotic cell death, suggesting the presence of a functional Fas receptor. In addition, proteasome inhibitor-induced apoptosis was prevented by the addition of antagonistic anti-FasL antibody (4A5) or z-IETD.fmk, a potent inhibitor of caspase-8, indicating the involvement of the Fas receptor-ligand apoptotic signaling system in proteasome inhibitor-mediated apoptosis. Thus, it is suggested that proteasome inhibitors cause the accumulation of c-Myc protein which induces transiently FasL message to stimulate the Fas receptor-ligand apoptotic signaling pathway.
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PMID:Proteasome inhibitors induce Fas-mediated apoptosis by c-Myc accumulation and subsequent induction of FasL message in human glioma cells. 1152 96

Identifying genes upregulated in lead-resistant cells should give insight into lead toxicity and cellular protective mechanisms and may also result in identification of proteins that may be useful as biomarkers. Glial cells are thought to protect neurons against heavy metals. Rat glioma C6 cells share many properties of normal glial cells. To identify and analyze genes upregulated in a lead-resistant variant, PbR11, suppression subtractive hybridization (SSH) between mRNAs of wild-type and PbR11 cells was performed. Sequencing and database searches identified three genes, thrombospondin-1, heparin sulfate 6-sulfotransferase, and neuropilin-1, which play important roles in angiogenesis and axon growth during development. Two genes, HSP90 and UBA3, are involved in the ubiquitin-proteosome system. One gene was identified as that of a rat endogenous retrovirus and another, 2C9, is a transcript expressed in fos-transformed cells. PbR11 also overexpresses c-fos. Expression of these genes and effects of short-term lead exposure (24 h, up to 600 microM) on their expression in C6 cells was examined. The rat endogenous retrovirus and 2C9 are expressed only in PbR11 cells, and show no expression, either constitutive or lead-induced, in wild-type C6 cells. HSP90 is expressed at low level constitutively in C6 cells, but can be induced in a dose-dependent manner by lead. In contrast, thrombospondin-1 is repressed in a dose-dependent manner by lead. The other genes (HS6ST, neuropilin, and UBA3) show low constitutive expression and are neither upregulated nor downregulated by exposure to lead. We suggest that neuropilin-1, heparin sulfate 6-sulfotransferase, and thrombospondin-1 may be important targets for lead-induced developmental neurotoxicity.
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PMID:Genes upregulated in lead-resistant glioma cells reveal possible targets for lead-induced developmental neurotoxicity. 1160 5

The mechanism by which hypoxia induces gene transcription involves the inhibition of hypoxia-inducible factor (HIF)-1alpha prolyl hydroxylase activity, which prevents von Hippel-Lindau (vHL)-dependent targeting of HIF-1alpha to the ubiquitin-proteasome pathway. HIF-1alpha is stabilized, translocates to the nucleus, interacts with hypoxia-responsive elements, and promotes the activation of target genes. This report shows that cyclosporin A (CsA) interferes with the hypoxic signaling cascade in C6 glioma cells. CsA inhibits hypoxia-dependent gene transcription in a reporter gene assay and prevents the hypoxic accumulation of HIF-1alpha. Addition of the 530-603 C-terminal oxygen-dependent degradation (ODD) domain of HIF-1alpha to the green fluorescent protein (GFP) destabilized the protein in an oxygen-dependent manner. CsA prevented the hypoxic stabilization of an ODD.GFP fusion protein. An assay for 2-oxoglutarate-dependent dioxygenases was developed using a light mitochondrial kidney fraction as a source of enzyme. It uses the capacity of specific peptides to stimulate the degradation of [(14)C]2-oxoglutarate. CsA stimulated the enzymatic activity in the presence of a peptide that mimicked the 557-576 sequence of HIF-1alpha. The enzyme promoted [(35)S]vHL binding to glutathione S-transferase (GST).ODD fusion protein. This association increased in the presence of CsA. CsA effects were not observed when the proline residue corresponding to Pro-564 in the HIF-1alpha sequence was replaced by a hydroxyproline or an alanine residue. Finally, CsA increased vHL-ODD interaction during hypoxia. We conclude that CsA destabilizes HIF-1alpha by promoting hydroxylation of Pro-564 in the ODD domain. Such a mechanism may prevent hypoxic adaptation during CsA-induced nephrotoxicity and contribute to the adverse effects of this drug.
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PMID:Cyclosporin A prevents the hypoxic adaptation by activating hypoxia-inducible factor-1alpha Pro-564 hydroxylation. 1258 29

Multiple system atrophy (MSA) is characterized by the formation of oligodendroglial cytoplasmic inclusions (GCIs) consisting of alpha-synuclein filaments. AlphaB-crystallin, a small chaperone protein that binds to unfolded proteins and inhibits aggregation, has been documented in GCIs. We investigated the relative abundance and speciation of alphaB-crystallin in GCIs in MSA brains. We also examined the influence of alphaB-crystallin on the formation of cytoplasmic inclusions in cultured glial cells. Immunohistochemistry and confocal microscopy revealed alphaB-crystallin is a prominent component of GCIs, more abundant than in Lewy bodies in Lewy body dementia. One- and two-dimensional gel electrophoresis and mass spectrometric analysis of GCIs immunopurified from MSA brains indicated that alphaB-crystallin is a major protein component with multiple post-translationally modified species. In cultured C6 glioma cells treated with the proteasomal inhibitor, lactacystin, to induce accumulation of ubiquitinated proteins, a subset of cells showed increased cytoplasmic staining for alphaB-crystallin. Proteasome-inhibited cells transfected with GFP-tagged alpha-synuclein resulted in ubiquitin- and alphaB-crystallin-positive aggregates resembling GCIs in MSA brains. Our results indicate that alphaB-crystallin is a major chaperone in MSA, and suggest a role of the protein in the formation of inclusion bodies in glial cells.
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PMID:Alpha B-crystallin is a major component of glial cytoplasmic inclusions in multiple system atrophy. 1563


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