Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of mouse hepatoma (Hepa) cells with heme or cadmium chloride in serum-free medium causes a rapid increase in the steady-state level of heme oxygenase (HO) messenger RNA. This increase is both dose- and time-dependent. Maximum accumulation of HO mRNA is observed 3 h after addition of either agent. Treatment of Hepa cells with heme or CdCl2 also stimulates the transcription of the HO gene, as judged by in vitro nuclear transcription run-on assays. The maximum rate of HO gene transcription occurs 2 h after treatment with either agent. Comparison of the relative increase in the rate of HO gene transcription with the relative increase in the level of HO mRNA demonstrates that transcriptional activation is the primary mechanism by which heme and cadmium produce the accumulation of HO mRNA in Hepa cells. Cadmium may also influence other processes involved in the expression of HO, since the time course of mRNA accumulation diverges from that of gene transcription. However, neither heme nor cadmium alters the rate of HO mRNA degradation. Cobalt chloride and heat shock, which are potent inducers of HO mRNA in rat liver and rat C6 glioma cells, respectively, have only a small effect on the level of HO mRNA in mouse hepatoma cells.
 ...
PMID:Transcriptional activation of the heme oxygenase gene by heme and cadmium in mouse hepatoma cells. 270 93

We have found that the small stress protein, hsp27, exists in extracts of U251 MG human glioma cells in two forms: a large or aggregated form (L-hsp27, 300-400 kDa) and a small or dissociated form (S-hsp27, < 70 kDa), as indicated by centrifugation on sucrose density gradients. Dissociation of L-hsp27 to S-hsp27 was enhanced by incubation of cells with phorbol 12-myristate-13 acetate, interleukin-1 alpha, tumor necrosis factor alpha, or okadaic acid, all of which are known to enhance or mimic the effects of phosphorylation of hsp27 without stimulation of its synthesis. Exposure of cells to chemical stressors, namely, NaAsO2 and CdCl2, also enhanced the dissociation of L-hsp27. hsp27 that had been labeled with [32P]H3PO4 in U251 MG cells was detected mostly in fractions that contained S-hsp27, and the incorporation of radioactivity to S-hsp27 was enhanced under conditions that stimulated the dissociation of L-hsp27. L-hsp27 present in the (NH4)2SO4 fraction (0-50% saturation) of cell extracts were dissociated to 32P-labeled hsp27 when incubated in the presence of [gamma-32P]ATP and Mg2+. These results indicate that the molecular configuration of hsp27 in cells is determined in part by phosphorylation and dephosphorylation of this protein by protein kinase(s) and phosphatase(s) and, moreover, that the rapid dissociation of the aggregated form of hsp27 by phosphorylation might be involved in a cellular defense mechanism for protection against stress.
 ...
PMID:Dissociation as a result of phosphorylation of an aggregated form of the small stress protein, hsp27. 815 58

The sensitive and specific biochemical indicators for assessing chemical-induced neurotoxic insults in cell culture models have not been sufficiently explored. This study was designed to assess the usefulness of glia-specific beta-S100 protein and neuron-specific enolase (NSE) as indices of in vitro neurotoxicity of heavy metals. Glioma C6 and neuroblastoma N18TG-2 cells were grown in Dulbecco's modified Eagle's medium containing various concentrations of mercuric chloride (HgCl2) or cadmium chloride (CdCl2) for 5 days. Toxic response patterns of the neurospecific endpoints (beta-S100 and NSE), which were monitored with enzyme immunoassays, were compared with those of the non-neurospecific endpoints such as cell viability, total cellular protein, lactate dehydrogenase (LDH) activity, and cumulative glucose consumption in the two cell lines. Both HgCl2 and CdCl2 produced dose-dependent inhibition of neurospecific endpoints and non-specific endpoints. However, by ranking the EC50 values (effective concentration producing half-maximal inhibition) for various endpoints, the lowest values were found for beta-S100 in C6 cells, and for NSE in N18TG-2 cells. In lower and intermediate concentrations, the inhibitory effects of the heavy metals on the content of beta-S100 and NSE occurred in the absence of any detectable effect on intracellular LDH activity, and independently of total cellular protein inhibition. The sensitive and excess responses of the neurospecific endpoints relative to that of the non-specific endpoints may reflect the specific neurotoxic insults of the heavy metals on the cultured cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neuron and glial cell marker proteins as indicators of heavy metal-induced neurotoxicity in neuroblastoma and glioma cell lines. 823 98

The 9L rat glioma cells grown in culture, when subjected to a mechanical injury (scratch wound) and/or a chemical injury (CdCl2) manifest changes which are characteristic of an astrocyte reaction (astrogliosis) in the central nervous system. Such changes include cell hypertrophy and an increase in immunostaining for the astrocytic marker proteins, glial fibrillary acidic protein and J1-31 antigen. Mitochondria also increase in size and number, and the endoplasmic reticulum expands in area. These mechanical and chemical injuries are coordinated, and act synergistically to induce a considerably more intense astroglial reaction by 9L cells than can be elicited with either injurious agent alone, and this occurs without any interactions with microglia, neurons or oligodendroglia. The phenomenon suggests that more than one transcriptional mechanism is involved in the activation of astrocytes, and that mechanical and CdCl2-induced injuries, respectively, probably affect different receptors and second- and third-messenger pathways. There are a number of questions concerning the molecular biology of reactive astrocytes which can be addressed through the use of the 9L rat glioma cell model. This model offers certain advantages over primary cultures of astrocytes, namely a low basal level of reactivity (because the cells are not subjected to mechanical injury prior to experimentation), an absence of contaminating microglial cells, greater ease of reproducibility of results, lower costs and avoidance of the use of animals.
 ...
PMID:Up-regulation of reactive astrogliosis in the rat glioma 9L cell line by combined mechanical and chemical injuries. 936 21

The effects of diethyl maleate and buthionine sulfoximine, agents that lower cellular levels of glutathione, on expression of hsp27 and alphaB crystallin in response to stress were studied. When C6 rat glioma cells were treated with 100 microM arsenite for 1 h, accumulation of the two proteins, estimated by specific immunoassays, was markedly enhanced by additional exposure to 1 mM diethyl maleate or 2.5 mM buthionine sulfoximine. The latter also increased heat- and CdCl2-induced accumulation of hsp27 and alphaB crystallin. Stress-induced accumulation of hsp70, estimated by Western blotting analysis, was also enhanced by these agents. Northern blotting analysis revealed increase in levels of mRNAs for hsp27, alphaB crystallin and hsp70. The period of heat shock element (HSE)-binding activity of heat shock factor (HSF) stimulated by arsenite was extended by addition of diethyl maleate and buthionine sulfoximine. The induced phosphorylated state of HSF1 was also prolonged by diethyl maleate. Although exposure of cells to diethyl maleate alone for 1 h caused neither accumulation of hsp27, alphaB crystallin and hsp70 nor expression of mRNAs for these proteins, HSE-binding activity of HSF was stimulated. However, the activated HSF was not phosphorylated. These results suggest that diethyl maleate induces an intermediate state of HSF that binds to HSE but is transcriptionally inert. The mechanism is unclear but the levels of glutathione in cells that were exposed to diethyl maleate or buthionine sulfoximine were markedly decreased.
 ...
PMID:Enhancement of expression of stress proteins by agents that lower the levels of glutathione in cells. 956 90

Curcumin, a major component of turmeric, a seasoning commonly used in Indian food, and a known antioxidant, anti-inflammatory and anti-carcinogenic agent, is a potent stimulator of the stress-induced expression of Hsp27, alphaB crystallin and Hsp70. When C6 rat glioma cells were exposed to arsenite (100 microM for 1 h), CdCl2 (100 microM for 1 h) or heat (42 degrees C for 30 min) in the presence of 3-10 microM curcumin, induction of the synthesis of all three proteins was markedly stimulated, as detected by specific immunoassays, Western blot analysis and Northern blot analysis. A gel mobility shift assay revealed that curcumin prolonged the stress-induced activation of the heat shock element-binding (HSE-binding) activity of heat shock transcription factor (Hsf) in the cultured cells. The stimulatory effect of curcumin on the responses to stress was also observed in BRL-3A rat liver cells and Swiss 3T3 mouse fibroblasts. Induction of Hsp27, alphaB crystallin and Hsp70 in the liver and adrenal glands of heat-stressed (42 degrees C for 20 min) rats was also enhanced by prior injection of curcumin (20 mg/kg body weight). As curcumin is a potent inhibitor of arachidonic acid metabolism, it is suggested that the mechanism of the stimulation by curcumin of the stress responses might be similar to that of salicylate, indomethacin and nordihydroguaiaretic acid.
 ...
PMID:Stimulation of the stress-induced expression of stress proteins by curcumin in cultured cells and in rat tissues in vivo. 976 55

The levels of Hsp27 and alphaB-crystallin in C6 rat glioma cells, that had been heated at 43 degrees C for 30 min with a subsequent culture for 16 h at 37 degrees C, were markedly increased. The exposure of the cells to a low concentration (0.1-3 microg/ml) of anisomycin for a few hours after heat stress stimulated the accumulation of the small stress proteins Hsp27 and alphaB-crystallin, but not that of Hsp70. The levels of mRNAs for Hsp27 and alphaB-crystallin but not that for Hsp70 increased in cells that had been exposed to heat and subsequently for 2 h to 0.1-3 microg/ml anisomycin. The results of a reporter assay, using an alphaB-crystallin promotor fused to a luciferase reporter gene, suggested that the increase in level of alphaB-crystallin mRNA was due to the production of new mRNA. The activation of the binding of heat shock factors to heat shock elements induced in cells that had been heat stressed was barely affected by subsequent exposure to anisomycin at 0.3 microg/ml. The stimulatory effects of anisomycin were also observed in cells that had been exposed to NaAsO2 or CdCl2. The active form of p38 mitogen activated protein (MAP) kinase was increased in cell that had been subjected to heat shock and subsequent exposure to 0.3 microg/ml of anisomycin. The heat-induced accumulations of Hsp27 and alphaB-crystallin were also stimulated by cycloheximide, another stimulator of p38 MAP kinase. SB202190, a specific inhibitor of p38 MAP kinase, suppressed the stimulation by anisomycin of the heat stress-induced expressions of Hsp27 and alphaB-crystallin. These results suggest that the signal transduction pathway of the stress-induced expressions of Hsp27 and alphaB-crystallin in C6 glioma cells includes a process that is sensitive to p38 MAP kinase.
 ...
PMID:Selective stimulation of Hsp27 and alphaB-crystallin but not Hsp70 expression by p38 MAP kinase activation. 1054 59

The pharmacological properties of a specific agmatine uptake mechanism were investigated in the human glioma cell line SK-MG-1 and compared with those of the putrescine transporter expressed by the same cells and with those of several other organic cation transport systems or ion channels reported in the literature. The specific accumulation of [14C]agmatine at 37 degrees C above nonspecific accumulation at 4 degrees C was energy-dependent and saturable with a Vmax of 64.3+/-3.5 nmol/min per mg protein and a Km of 8.6+/-1.4 microM. Specific accumulation was attenuated by replacement of extracellular Na+ by choline by 65%, not affected by lithium and enhanced by replacement by sucrose. Phentolamine, clonidine, 1,3-di(2-tolyl)guanidine, histamine, putrescine, spermine and spermidine were inhibitors of specific [14C]agmatine accumulation. In contrast, corticosterone, desipramine, O-methylisoprenaline, cirazoline, moxonidine, L-arginine, L-lysine, verapamil, nifedipine and CdCl2 at concentrations up to 10 mM failed to inhibit specific [14C]agmatine accumulation, thus excluding that the latter is mediated by amino acid or monoamine carriers, by Ca2+ channels or by the organic cation transporters OCT1, OCT2, OCT3, OCTN1 or OCTN2. The pattern of activity of inhibitory compounds was also different from that determined for specific putrescine accumulation found in the same cells (Km 1.3+/-0.1 microM, Vmax 26.1+/-0.4 nmol/min per mg protein) ruling out an identity of the specific [14C]agmatine and [14C]putrescine accumulation mechanisms. It is concluded that specific accumulation of agmatine in human glioma cells is mediated by a specific transporter whose pharmacological properties are not identical to those of the agmatine transporter previously identified in rat brain synaptosomes and to other so far known carrier mechanisms for organic cations and ion channels. The agmatine uptake system may be important for the regulation of the extracellular concentration of agmatine in man.
 ...
PMID:Agmatine and putrescine uptake in the human glioma cell line SK-MG-1. 1141 62

We previously showed that the aggregated form of Hsp27 in cultured cells becomes dissociated as a result of phosphorylation with various types of stress. In order to clarify the signal transduction cascade involved, the effects of various inhibitors of protein kinases and dithiothreitol on the dissociation of Hsp27 were here examined by means of an immunoassay after fractionation of cell extracts by sucrose density gradient centrifugation. The dissociation of Hsp27 induced by exposure of U251 MG human glioma cells to metals (NaAsO2 and CdCl2), hypertonic stress (sorbitol and NaCI), or anisomycin, an activator of p38 mitogen-activated protein (MAP) kinase, was completely suppressed by the presence of SB 203580 or PD 169316, inhibitors of p38 MAP kinase, but not by PD 98059 and Uo 126, inhibitors of MAP kinase kinase (MEK), nor by staurosporine, Go 6983, and bisindolylmaleimide I, inhibitors of protein kinase C. Phorbol ester (PMA)-induced dissociation of Hsp27 was completely suppressed by staurosporine, Go 6983, or bisindolylmaleimide I and partially suppressed by SB 203580, or PD 169316 but not by PD 98059 or Uo 126, indicating mediation by 2 cascades. The presence of 1 mM dithiothreitol in the culture medium during exposure to chemicals suppressed the dissociation of Hsp27 induced by arsenite and CdCl2 but not by other chemicals. These results suggest that the phosphorylation of Hsp27 is catalyzed by 2 protein kinases, p38 MAP kinase-activated protein (MAPKAP) kinase-2/3 and protein kinase C. In addition, metal-induced signals are sensitive to reducing power.
 ...
PMID:Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27. 1152 38

The induction of apoptotic cell death by cadmium was investigated in eight mammalian cell lines. Great differences in the cytotoxicity of cadmium were found with different cell lines: Rat C6 glioma cells turned out to be most sensitive with an IC50-value of 0.7 microM, while human A549 adenocarcinoma cells were relatively resistant with an IC50-value of 164 microM CdCl2. The mode of cadmium-induced cellular death was identified to involve apoptotic DNA fragmentation in three cell lines, i.e., in C6 glioma cells, E367 neuroblastoma cells and NIH3T3 fibroblasts. In C6 glioma cells, this process was investigated in detail. Internucleosomal DNA-fragmentation occurred 40 h after application of CdCl2 and was concentration-dependent between 1-100 microM CdCl2, followed by a decrease at higher concentrations due to necrotic processes. Apoptotic chromatin-condensation and nuclear fragmentation was observed 48 h after application of 2.5 microM CdCl2. Furthermore, cadmium (1 microM, 48 h) caused a breakdown of the mitochondrial membrane potential as shown by the decline in mitochondrial uptake of rhodamine 123. Also, we found an activation of caspase 9, a protease known to be activated in apoptotic processes following mitochondrial damage. Besides Cd2+, other toxic heavy metal ions (Hg2+, Pb2+, Ni2+, Fe2+, CrO4(2-), Cu2+ or Co2+) did not induce apoptotic DNA fragmentation in C6 cells. The only exception was Zn2+ which caused apotosis at high concentrations (>150 microM) whereas it protected against cadmium-induced apoptosis at low concentrations (10-50 microM).
 ...
PMID:Cadmium-induced apoptosis in C6 glioma cells: mediation by caspase 9-activation. 1186 19


1 2 Next >>