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)

A heat shock element is located in the 5'-flanking region of the rat heme oxygenase gene (HO gene). The incubation of rat glioma cells at 42 degrees C or with hemin at 37 degrees C increased the levels of heme oxygenase mRNA within 1 h and produced a maximum at 3 h (at least a 20-fold increase). In both treatments, the heme oxygenase activity started to increase after a lag period of about 1 h and reached a maximum value at 5 h. There was an apparent additive effect of both treatments on the heme oxygenase induction. Studies with actinomycin D and cycloheximide suggested that both heat shock and hemin acted at the transcriptional level to induce heme oxygenase. Therefore, we analyzed the transient expression of chimeric fusion genes harboring the promoter of the rat HO gene ligated to the Escherichia coli gene gpt in rat glioma cells and in K1735 mouse amelanotic melanoma cells. The 5'-flanking region of the rat HO gene bearing the heat shock element conferred the heat inducibility of gpt RNA production in both cell lines; however, hemin treatment did not induce gpt RNA. These results indicate that rat heme oxygenase is a heat shock protein and that hemin induces heme oxygenase through a different mechanism from heat shock.
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PMID:Transcriptional control of rat heme oxygenase by heat shock. 365 94

Previously we found that ethanol increases expression of the constitutive 70-kDa heat shock protein (Hsc70) in NG108-15 neuroblastoma x glioma cells. We suggested that known ethanol actions on cellular protein trafficking may relate to Hsc70 induction because Hsc70 functions as a molecular chaperone. Here we use a subtractive hybridization protocol to isolate ethanol-responsive genes (EtRGs). Northern blot hybridization verified ethanol-induced increases in mRNA abundance for five cDNA clones isolated from ethanol-treated NG108-15 neuroblastoma x glioma cells. DNA sequence analysis identified one EtRG as 94-kDa glucose-regulated protein (GRP94), a member of the "glucose-responsive" subgroup of stress proteins. Other identified EtRGs included an insulin-induced growth-response protein gene and an intracisternal A-type particle gene. Sequence analysis of the remaining two EtRGs showed no homology in DNA sequence databases. All EtRGs showed wide tissue expression, except SL64, which was not detected in Northern blot analyses of adult mouse or rat tissues. Ethanol also increased mRNA abundance for 78-kDa glucose-regulated protein (GRP78), a molecular chaperone known to function in glycoprotein trafficking and usually coordinately regulated with GRP94. However, ethanol induced GRP94 more than GRP78, a pattern distinct from those of other inducers of these genes. All EtRGs, including GRP94 and GRP78, showed similar ethanol concentration-dependent increases in mRNA abundance. In contrast, thapsigargin and other inducers of glucose-responsive proteins increased GRP94 and GRP78 mRNA levels without altering expression of other EtRGs. Our studies demonstrate that several molecular chaperones constitute a subset of EtRGs. Ethanol appears to regulate these EtRGs by a unique mechanism, rather than one shared by classical inducers of stress proteins.
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PMID:Ethanol-responsive genes in neural cells include the 78-kilodalton glucose-regulated protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) molecular chaperones. 796 74

In C6 rat glioma cells, the n-alcohols methanol, ethanol, propanol, and butanol and the aromatic alcohol phenol all induce heat shock proteins (HSPs) of high molecular mass (68, 70, 90, and 110 kDa) when applied for 1 hr. The lowest alcohol concentrations that induce HSP synthesis cause about 20% cell death, as determined by neutral red assay. HSP induction thus occurs at alcohol concentrations close to the highest tolerable dose. The cytotoxicity and the potential of alcohols to induce the synthesis of HSPs increase with chain length and are correlated with the lipophilicity of the alcohols. A clear structure-activity relationship is observed for both parameters. A calculation of the putative membrane concentrations of these alcohols reveals that cytotoxic effects (50% cell death) occur at nearly the same membrane concentration (approximately 0.2 M). This also holds true for the lowest HSP 68-inducing alcohol concentrations, but at a lower concentration (approximately 0.12 M). The activities of major proteinases are affected by both heat shock and alcohols. The effects of alcohols also depend on the lipophilicity of the alcohols. Effective concentrations again are close to the highest tolerable dose. The stress reactions measured in terms of significant changes in HSP synthesis and proteinase activity provide information about the mechanisms by which toxic agents act on the cell.
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PMID:Heat shock response and cytotoxicity in C6 rat glioma cells: structure-activity relationship of different alcohols. 830 78

To understand the significance of the accumulation of alpha B-crystallin in Rosenthal fibers within astrocytes, the expression and metabolism of alpha B-crystallin in glioma cell lines were examined under the conditions of heat and oxidative stress. alpha B-crystallin mRNA was increased after both stresses, and alpha B-crystallin protein moved from a detergent-soluble to a detergent-insoluble form. In addition, Western blotting of Alexander's disease brain homogenates revealed that the 27-kd heat shock protein (HSP27), which is related to alpha B-crystallin, accumulates along with alpha B-crystallin. The presence of HSP27 in Rosenthal fibers was directly demonstrated by immunohistochemistry. Our results suggest that astrocytes in Alexander's disease may be involved in an as yet unknown kind of stress reaction that causes the accumulation of alpha B-crystallin and HSP27 and results in Rosenthal fiber formation.
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PMID:Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers. 839 18

AlphaB-crystallin and the small stress protein, heat shock protein of 27 kDa (HSP27), share structural similarities and are coordinately induced by classical stress stimuli. We have recently observed that hypertonic stress produced by high NaCl concentrations selectively induces alphaB-crystallin in glial cells. To examine divergence of the functional properties of these two related proteins, we have constructed stable alphaB-crystallin-expressing glial cell lines from the U-251 MG glioma cells, which are normally deficient in alphaB-crystallin expression but constitutively express HSP27. These transfected cells lines are more resistant to acute hypertonic stress than the parental line from which they were derived. Moreover, the parental line acclimates to stepwise increases in hypertonicity and upregulates endogenous alphaB-crystallin in the process but not HSP27. The overexpression of HSP27 and alphaB-crystallin in NIH/3T3 fibroblasts, a cell line that normally expresses little alphaB-crystallin and no HSP27, does not result in increased survival. This suggests that alphaB-crystallin interacts with cell-type specific mechanisms to aid in protection from hypertonic stress.
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PMID:AlphaB-crystallin protects glial cells from hypertonic stress. 863 73

The effect of intracellular pH (pHi) on heat shock protein (HSP) synthesis was investigated in C6 rat glioma cells. pHi changes were analysed by means of fluorescence spectroscopy in a perfused monitoring system allowing continuous measurements before, during and after treatments. HSP induction was determined by means of Western blots and autoradiographs. A 20 min heat shock (HS) of 44 degrees C decreased the pHi from 7.36 to 7.05 during exposure [17] and elicited the synthesis of heat shock proteins 2-8 h later. A pHi decrease, brought about by low extracellular pH (pHe) of 4.5 and 5.0 or 5.5, induced HSP synthesis after 1 h or 3 h, respectively. During these treatments, pHi decreased to values significantly lower than that caused by HS. Three h exposure to pHe 6.2, however, was not inductive. These results indicate that the heat shock-induced pHi decrease alone is not sufficient to stimulate HSP synthesis. In order to investigate the effect of alkaline pHi on the induction of HSP by heat, pHi was increased prior to HS treatments. Preincubation of cells at pHe ranging from 6.8 to 8.0 had little effect on pHi and on HSP synthesis. A shift of pHi to more alkaline values was achieved by adding the H+/Na+ exchanger monensin at alkaline pHe. Twenty microM monensin raised the pHi and inhibited the HSP induction depending on the pHe values: as pHe was increased from pH 7.2 to 8.0 HSP synthesis was increasingly inhibited. Monensin also diminished the HS-induced drop of pHi particularly at higher pHe. The result showed that neither a lower pHi nor a drop of pHi during HS is a necessary prerequisite for the induction, whereas alkalosis inhibits the synthesis of HSP.
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PMID:Heat shock protein synthesis is affected by intracellular pH: inhibition by monensin-induced alkalosis in C6 rat glioma cells. 881 51

Acid proteinases of C6 rat glioma cells were analyzed by means of gelatine polyacrylamide electrophoresis with respect to their responses to stress (heat shock and butanol). Proteinase activities on gelatine gels were characterized by their molecular masses. pH-optima, isoelectric points and reactions to inhibitors. Four bands of 25, 35 and 65/85 kDa most probably represent active and proforms as well as precursor complexes of lysosomal cysteine proteinases with pH optima between 4.0 and 5.0. The 25-kDa band seems to contain cathepsin L and B, the 35-kDa band proforms of cathepsin L and B and the 65/85-kDa bands possibly precursor complexes of cathepsin L and B. After 30-min heat shocks of different temperatures (40-50 degrees C), the 35-kDa activity increased, whereas the 65/85-kDa activity decreased after exposure to 42 and 44 degrees C, which also caused a strong increase in the level of the inducible heat shock protein of 68 kDa (HSP 68). The alterations of the proteinase activities and the increases of the HSP 68 levels occur at heat shock treatments that cause cell death in about 25-40% of the population as determined by Trypan blue staining. HSP 68 induction and proteinase activity changes were also observed 12 hr after a 1-hr treatment with different butanol concentrations (0.14-0.16 M). Kinetics of the response to a 30-min heat shock (44 degrees C) revealed a maximal decrease of the 35-kDa and a maximal increase of the 65/85-kDa activities after 12 hr recovery. When cells were exposed to repeated heat shocks (44 degrees C) at 12-hr intervals, the HSP 68 level further increased, whereas the 35-kDa and 65/85-kDa proteinase activities did not change. This result indicates a role of HSP 68 (or other HSPs) in the processing or stability of the putative cathepsin precursors (65/85-kDa complexes).
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PMID:Stress response of lysosomal cysteine proteinases in rat C6 glioma cells. 922 78

Seven agents were analyzed with respect to their ability to induce heat shock protein (HSP) synthesis in C6 rat glioma cells. Induction of HSP synthesis was correlated with cytotoxicity and lipophilicity of the substances. In addition to the first four n-alcohols (methanol, ethanol, propanol and butanol) and phenol, whose capacity to induce HSP was analyzed earlier (Neuhaus-Steinmetz et al., 1994. Mol. Pharmacol. 45, 36-41), isopropanol, 1,4-dinitrophenol (DNP), diethylstilbestrol (DES), carbonylcyanide-m-chlorophenylhydrazone (CCCP), rotenone, paracetamol and acetyl salicylic acid (ASA) induced HSP synthesis after a 1-h incubation at a substance-specific concentration. The maximal induction of HSPs was closely correlated with the cytotoxicity of all substances and occurred when cell viability was reduced to 75 +/- 11% of the controls. Cytotoxicity and the ability to induce HSP were correlated with the lipophilicity of the alcohols, phenol, rotenone and paracetamol. Calculation of the hypothetical membrane concentrations of these compounds yielded a nearly equal value (0.54 +/- 0.13 M), indicating that interaction of substances with lipophilic cellular compounds, such as membranes or lipophilic core regions of proteins, is a critical step leading to HSP induction. This assumption is supported by a correlation between HSP induction and protein denaturation by the different alcohols (Herskovits et al., 1970. J. Biol. Chem. 245, 2588-2598). We assume that the amount of misfolded proteins induced by these lipophilic agents is responsible for the induction of HSP synthesis. ASA, DNP and CCCP induced HSP at lower concentrations than substances with a similar lipophilicity, which may be due to effects which add to the misfolding of proteins or to other signal pathways.
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PMID:Heat shock protein induction by certain chemical stressors is correlated with their cytotoxicity, lipophilicity and protein-denaturing capacity. 935 37

The expression and the nuclear translocation of the constitutive heat shock protein 70 (Hsc70) were determined during the cell cycle in synchronized rat astrocytomic C6 glioma cells. Cells were first shifted to the G0 by serum starvation. Twelve hours after a subsequent growth stimulation by transfer to 20% newborn calf serum, about 50% of the cells entered S phase. Western blot analysis with different monoclonal antibodies showed that only the constitutively expressed and moderately stress-activated Hsc70 is induced during serum stimulation. Maximal cellular Hsc70 content (170% of the control) was observed in early to mid S phase followed by a drastic decline while cells pass through G2/M (20% of the control). Hsp70, the major heat-inducible heat shock protein in C6 cells, is not detected in either asynchronously proliferating, serum-starved or in serum-stimulated C6 cells. Analysis of the nuclear and cytoplasmic protein fractions showed a significant increase of Hsc70 translocation into the nucleus during early S phase. These results indicate a role for Hsc70 but not for Hsp70 in the process of S phase entry and/or progression in C6 cells under physiological conditions.
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PMID:Nuclear translocation of stress protein Hsc70 during S phase in rat C6 glioma cells. 967 44

Rat C6 glioma cells were stably transfected with a human cDNA encoding heat shock protein (HSP)70. Immunostaining revealed the presence of largely cytosolic HSP70 in C6-hsp70 cells, but not in control (vector transfected) C6-pTK cells. Induction of nitric oxide synthase (NOS-2) expression in C6-hsp70 cells, assessed by nitrite accumulation, was significantly reduced compared to control C6-pTK cells (25+/-8% of control cell induction, P < 0.005), when induced with a maximally stimulatory combination of bacterial endotoxin lipopolysaccharide (LPS) plus a mixture of three cytokines ("CM:" TNF-alpha, IL1-beta, and IFN-gamma). Immunostaining for the transcription factor NFkappaB p65 subunit revealed decreased cytokine-dependent nuclear uptake in HSP70 expressing cells compared to control cells. Activation of C6 cell NFkappaB by LPS plus CM required IkappaB degradation by the 20S proteasome, since NOS-2 expression was blocked by a selective proteasome inhibitor. In parental C6 cells, the presence of LPS plus CM caused a rapid (within 30 min) decrease in inhibitory IkappaB-alpha protein levels, and this loss was abolished by prior heat shock of the cells. In contrast, IkappaB-alpha levels in transfected cells were not modified by the expression of HSP70. These results demonstrate that constitutive HSP70 expression in glial cells can reduce NOS-2 induction, presumably due to inhibition of NFkappaB nuclear uptake. Furthermore, whereas prevention of decreases in IkappaB-alpha can account for the suppressive effects of heat shock, the results suggest that HSP70 blocks NOS-2 induction by interfering at a later step in the NFkappaB activation pathway.
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PMID:Suppression of glial nitric oxide synthase induction by heat shock: effects on proteolytic degradation of IkappaB-alpha. 970 Oct 55


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