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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Neuron and glial cell marker proteins as indicators of heavy metal-induced neurotoxicity in neuroblastoma and glioma cell lines. 823 98

Oligodendroglia-glioma hybrid cells (ROC-1) subjected to inhibition of glycolytic and oxidative ATP synthesis undergo a sequence of changes, including ATP depletion, parallel processes of cell swelling and blebbing, and finally plasma membrane disruption and cell death. The morphological and biochemical changes that follow ATP depletion were studied in the presence and absence of polyethylene glycol (M(r) 8,000), a nonpermeant oncotic agent. Polyethylene glycol prevented cell swelling and membrane blebbing. It significantly delayed, but did not prevent, the release of lactate dehydrogenase into the medium; it did not affect the fall in [ATP]. These results suggest that osmotic cell swelling may be a contributing factor in the loss of cell viability when ROC-1 cells are depleted of ATP.
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PMID:Protection of ROC-1 hybrid glial cells by polyethylene glycol following ATP depletion. 837 11

Oligodendrocytes (OLs) and their myelin membranes are the apparent injury targets in the putative human autoimmune disease multiple sclerosis. The basis for this selective injury remains to be defined. OLs in vitro have been shown to be susceptible to both tumor necrosis factor (TNF) and non-TNF-dependent immune effector mechanisms. The former involves initial nuclear injury (apoptosis); the latter, when mediated by activated T cells, involves initial cell membrane injury (lysis). In the current study, we determined whether human adult CNS-derived OLs could be protected from the above immune effector mechanisms by selected neurotrophic factors (CNTF, BDNF, NGF, NT-3, and NT-4/5) or cytokines demonstrated to protect from human or experimental autoimmune demyelinating diseases (beta-interferon [IFN], IL-10, and TGF-beta). Nuclear injury was assessed in terms of DNA fragmentation using a DNA nick-end-labelling technique; cell membrane injury was assessed by lactate dehydrogenase or chromium 51 release. MTT and cell counting assays were used to assess cell viability and cell loss, respectively. Amongst the neurotrophic factors and cytokines tested, only CNTF significantly protected the OLs from TNF-mediated injury. CNTF also protected the OLs from serum deprivation-induced apoptosis. CNTF, however, did not protect the OLs from injury induced by activated CD4+ T cells. CNTF also did not protect human fetal cortical neurons from serum deprivation or TNF-induced DNA fragmentation, nor did it protect the U251 human glioma cell line from DNA fragmentation induced by a combination of TNF and reduced serum concentration in the culture media. Our results indicate that potential protective effects of neurotrophic factors or cytokines on neural cell populations can be selective both for cell type involved and mechanism of immune-mediated injury. CNTF is the protective factor selective for nuclear-directed injury of OLs.
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PMID:Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. 871 18

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.
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PMID:Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. 901 Apr 29

An in vitro model of dissociated cerebral cultures, prepared from prenatal 15-16-days rat fetuses, was used to further characterize the neurotoxic effects caused by the antibiotic ionophore lasalocid-X-537A. The damage caused by lasalocid (1-2 microM, 2-4 hr) included swelling of perikarya, followed by cytolysis of most neurons present in the cultures. The neuronal damage was dose-dependent, noticeable at concentrations above 0.5 microM, and was more pronounced in established cultures (14 days in vitro-DIV) than in younger ones (7 DIV). Unlike neurons, no damage was observed in glia and other non-neuronal cells present in the cultures by exposure to 2 microM lasalocid. Moreover, the drug was not toxic for cultures of rat astrocytes and C6 glioma cells. Another calcium ionophore A-23187 (calcimycin, 1 microM), destroyed both neuronal and non-neuronal cells within 1 hr. Ca2+ influx was increased by 140% in cultures exposed to lasalocid (1.5 microM). The lasalocid neurotoxic effects were neither inhibited by 10 microM nimodipine (a calcium channel antagonist) nor by 10 microM 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)(a non-N-methyl-D-aspartic acid (NMDA) receptor antagonist), but were exclusively blocked by 10 microM MK-801 (a non-competitive NMDA receptor/channel antagonist). The neurotoxicity induced by lasalocid was further confirmed by measurements of lactate dehydrogenase (LDH) released into the media. Lasalocid (1.5 microM) induced the release of both LDH and arachidonic acid (AA) (by 8 and 4 fold of control values, respectively), and this was blocked by MK-801 but not by CNQX. These results are in according with the observations that activation of calcium influx through the NMDA receptor leads to activation of phospholipase A2 (PLA2) and release of AA. In contrast, MK-801 did not block the release of either LDH or AA mediated by the calcium ionophore A-23187 (1 microM) in these cultures. [3H]-MK-801 binding to washed rat cortical membranes, a measure of direct interaction with the NMDA receptor/channel complex, was not affected by lasalocid either alone or in the presence of glutamate and glycine. [3H]-D-aspartate release, a measure of excitatory amino acid (EAA) secretion mediated by NMDA receptor activation, was increased by lasalocid and could be blocked by MK-801. These observations suggest that lasalocid induces selective neurotoxicity, which involves the NMDA receptor/channel complex, possibly indirectly, resulted in elevated intracellular Ca2+ levels and the subsequent glutamate or aspartate release.
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PMID:Selective neurotoxicity induced by the ionophore lasalocid in rat dissociated cerebral cultures, involvement of the NMDA receptor/channel. 908 12

1. In C6 glioma cells exposed to chemical hypoxia a massive release of lactate dehydrogenase (LDH) occurred at 3 and 6 h, coupled with an increased number of propidium-iodide positive dead cells. 2. Extracellular Na+ removal, which activates the Na(+)-Ca2+ exchanger as a Na+ efflux pathway and prevents Na+ entrance, significantly reduced LDH release and the number of propidium iodide positive C6 cells. 3. During chemical hypoxia, in the presence of extracellular Na+ ions, a progressive increase of [Ca2+]i occurred; in the absence of extracellular Na+ ions [Ca2+]i was enhanced to a greater extent. 4. The blockade of the Na(+)-Ca2+ exchanger by the amiloride derivative 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), lanthanum (La3+) and the Ca2+ chelator EGTA, completely reverted the protective effect exerted by the removal of Na+ ions on C6 glioma cells exposed to chemical hypoxia. 5. The inhibition of the Na(+)-Ca2+ antiporter enhanced chemical hypoxia-induced LDH release when C6 glioma cells were incubated in the presence of physiological concentrations of extracellular Na+ ions (145 mM), suggesting that the blockade of the Na(+)-Ca2+ antiporter during chemical hypoxia can lead to increased cell damage. 6. Collectively, these results suggest that activation of the Na(+)-Ca2+ exchanger protects C6 glioma cells exposed to chemical hypoxia, whereas its pharmacological blockade can exacerbate cellular injury.
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PMID:Pharmacological evidence that the activation of the Na(+)-Ca2+ exchanger protects C6 glioma cells during chemical hypoxia. 915 41

Addition of 30mM glutamate to the culture medium decreased growth of rat glioma C6 cells accompanied by a decrease of DNA synthesis and an increase of lactate dehydrogenase (LDH) detected in the conditioned medium. The presence of 1 microM deprenyl attenuated the glutamate effect on cell growth only during the first 24-48 h incubation and had a minor influence on the glutamate-induced decrease of DNA synthesis. Clorgyline (1 microM) potentiated glutamate-induced DNA synthesis during the first 24 h incubation without significant influence on the cell growth. Deprenyl slightly attenuated the glutamate-induced LDH increase during 24 h incubation but potentiated the glutamate effect at 96 h. Clorgyline decreased the glutamate influence at 24 h and especially 96 h. All these effects were observed in the absence of exogenous monoamines in the culture medium. These results suggest that in transformed cells monoamine oxidase (MAO) inhibitors may influence processes of cell death via MAO-independent mechanisms.
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PMID:Modulation of glutamate neurotoxicity in the transformed cell culture by monoamine oxidase inhibitors, clorgyline and deprenyl. 956 11

Peroxynitrite triggers DNA single-strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of PARS depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, resulting in cell necrosis. Here, we demonstrate that inhibition of PARS with the novel, potent PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) protects against peroxynitrite-induced cell death (as measured by measurement of mitochondrial respiration and release of lactate dehydrogenase) in C6 glioma cells in vitro, and in a murine stroke model in vivo. Inhibition of PARS with INH2BP may represent a novel approach for the experimental therapy of stroke.
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PMID:Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development. 972 Oct 31

Expression of the lactate dehydrogenase A subunit (LDH-A) gene can be controlled by transcriptional as well as posttranscriptional mechanisms. In rat C6 glioma cells, LDH-A mRNA is stabilized by activation and synergistic interaction of protein kinases A and C. In the present study, we aimed to identify the sequence domain which determines and regulates mRNA stability/instability by protein kinase A and focused our attention on the 3'-untranslated region (3'-UTR) of LDH-A mRNA. We have constructed various chimeric globin/lactate dehydrogenase (ldh) genes linked to the c-fos promoter and stably transfected them into rat C6 glioma cells. After their transfection, we determined the half-life of transcribed chimeric globin/ldh mRNAs. The results showed that at least three sequence domains within the LDH-A 3'-UTR consisting of nucleotides 1286-1351, 1453-1471, and 1471-1502 are responsible for the relatively rapid rate of LDH-A mRNA turnover in the cytoplasm. Whereas chimeric globin/ldh mRNAs containing the base sequences 1286-1351 and 1453-1471 were not stabilized by (Sp)-cAMPS, an activator of protein kinase A, instability caused by the 1471-1502 domain was significantly reversed. Additional deletion and mutational analyses demonstrated that the 3'-UTR fragment consisting of the 22 bases 1478-1499 is a critical determinant for the (Sp)-cAMPS-mediated LDH-A mRNA stabilizing activity. Because of its functional characteristics, we named the 22-base region "cAMP-stabilizing region."
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PMID:Protein kinase A-regulated instability site in the 3'-untranslated region of lactate dehydrogenase-A subunit mRNA. 973 91

Using a cell culture model of the blood-brain barrier (BBB) we have evaluated the role of endothelial cell glutathione in protecting barrier integrity against nitric oxide (NO)-induced oxidative stress. The co-culture of human umbilical vein endothelial cells (ECV304) with rat (C6) glioma cells, or incubation with glioma cell or primary astrocytic conditioned medium, resulted in a decline in endothelial cell glutathione. Exposure to a single addition of NO gas induced a rapid breakdown in model barrier integrity in endothelial/glioma co-cultures. Addition of NO gas or tumour necrosis factor-alpha (TNF-alpha) also resulted in a loss of membrane integrity, as measured by an enhanced release of lactate dehydrogenase, only from endothelial cells treated with glioma conditioned medium. Furthermore, assessment of viability in endothelial cells grown alone or treated with glioma conditioned medium, by propidium iodide labelled flow cytometry. demonstrated no difference in the number of positively stained cells after NO exposure. These results indicate that when enhanced endothelial monolayer barrier formation occurs via astrocytic-endothelial interactions, cellular glutathione levels are decreased. This renders the barrier cells, under these conditions, more susceptible to oxidative stress but does no necessarily lead to greater cell death.
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PMID:Decreased endothelial cell glutathione and increased sensitivity to oxidative stress in an in vitro blood-brain barrier model system. 974 97


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