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)

Possible effects of tetanus toxin (TeTox) on voltage-activated Ca2+ channels of the mouse neuroblastoma cell line N1E-115 and of the neuroblastoma x glioma hybrid cell line NG108-15 have been investigated using the whole-cell voltage clamp technique. Similar to N1E-115 cells, differentiated NG108-15 cells express transient (T-type) as well as long-lasting (L-type) Ca2+ channels. Using various treatment protocols N1E-115 and NG108-15 cells were exposed to TeTox externally and by internal dialysis. In the cells treated with TeTox normal Ca2+ channel activity was present, as measured by the voltage-activated Ba2+ currents under voltage clamp conditions. In addition, intracellular microelectrode recordings showed that TeTox did not block the Ca2+ action potential in N1E-115 cells. It is concluded that TeTox, in contrast to previously reported results, does not affect voltage-activated T- and L-type Ca2+ channels in cultured neuronal cell lines. The results also indicate that Ca2+ channel block is unlikely to be an explanation for the block of neurotransmitter release by TeTox in vivo.
 ...
PMID:L- and T-type calcium channels in cultured neuronal cell lines are insensitive to tetanus toxin. 166 81

There is considerable literature on the pathogenesis of tetanus toxin poisoning; however, the mechanism of action and intracellular substrate of this toxin have not been defined. It was demonstrated that the NG-108 neuroblastoma x glioma cell line is a suitable model in which to study the mechanism of tetanus toxin action, from binding of the toxin to inhibition of transmitter release. Further, it has been shown that tetanus toxin pretreatment attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C (PKC) in this cell line. In the present study a 4-hr tetanus toxin pretreatment (10(-10)-10(-13) M) completely inhibited the mobilization of cytosolic PKC induced by a 30-min exposure to 10 microM neurotensin. Pretreatment with 10(-10) M tetanus toxin for periods as short as 1 hr was sufficient to attenuate the ability of neurotensin to mobilize cytosolic PKC; however, a 30-min pretreatment had no significant effect. At a concentration of 10(-11) M, it was necessary to pretreat the cells for greater than 1 hr to significantly attenuate neurotensin-mobilized PKC activity. The exact role that PKC plays in the secretory process is not yet known; however, these findings suggest that the effect of tetanus toxin on neurotransmitter release is accompanied by an alteration in PKC metabolism in differentiated NG-108 cells.
 ...
PMID:Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C activity in NG-108 cells. 181 11

Although the pathology of tetanus toxin poisoning has been linked to an inhibition of neurotransmitter release, the mechanism of this inhibition is unknown. The neuroblastoma x glioma hybrid cell NG-108 is an emerging model in which to study the biochemical effect of tetanus toxin on acetylcholine secretion. In differentiated as well as undifferentiated NG-108 cells, a 4 hr tetanus toxin (10(-8) M) pretreatment had no effect on basal levels of cyclic AMP or cyclic GMP. In addition, toxin pretreatment did not affect agonist induced increases in either cyclic nucleotide. Treatment of NG-108 cells for 4 hr with 10(-10) M tetanus toxin had no effect on the subsequently measured activity of cytosolic protein kinase C. However, a 4 hr pretreatment of undifferentiated or differentiated cells with tetanus toxin (10(-8) or 10(-10) M respectively) significantly attenuated the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C. Direct addition of tetanus toxin (10(-7)-10(-10) M) to isolated protein kinase C did not alter the ability of the enzyme to phosphorylate histone protein. These results suggest that one manifestation of tetanus toxin poisoning may be a disruption in protein kinase C metabolism.
 ...
PMID:Tetanus toxin attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C in NG-108 cells. 215 77

Differentiated neuroblastoma x glioma hybrid cells NG 108-15 express on their surface specific binding sites for tetanus toxin. 450 sites/cell with a KD of 2 x 10(-11) M were found under "physiological" conditions of pH and salt concentrations. A Hill coefficient of 1.1 indicated noncooperative binding. Specific binding of 125I-toxin to its sites could be prevented either by preincubation of the toxin with a neutralizing monoclonal antibody or by pretreatment of the cells with neuraminidase (Vibrio cholerae). To quantify the action of tetanus toxin on the stimulated release of 14C activity from differentiated cells preincubated with [14C]choline, a new type of perfusion device was designed which could be filled with cells growing in monolayers on Cytodex-3 microbeads. Tetanus toxin inhibited the stimulated 14C release in a time- and dose-dependent manner. A greater than 50% inhibition was found after 2 h of incubation with 10(-12) M toxin. The inhibitory action of tetanus toxin could be prevented with a monoclonal antibody to the toxin or with neuraminidase treatment of the cells. These results suggest that the neuraminidase-sensitive 2 x 10(-11) KD receptors are the productive receptors for tetanus intoxication in differentiated NG 108-15 cells. The possible chemical composition of these receptors is discussed. Differentiated NG 108-15 cells provide a useful model in which picomolar tetanus concentrations produce both measurable saturable binding and inhibition of potassium-evoked, acetylcholine release under physiological conditions of pH and salt concentrations.
 ...
PMID:Tetanus toxin binds with high affinity to neuroblastoma x glioma hybrid cells NG 108-15 and impairs their stimulated acetylcholine release. 282 18

A neuroblastoma cell line was assessed for its capacity to bind tetanus toxin (TT) by using immunofluorescence and flow cytometry to analyze cells on a single cell basis. A clone of Neuro 2a, N2AB-1, was shown to bind variable amounts of TT per cell and this binding could be saturated by increasing doses of the toxin. Toxin binding was specific for neuronal cells, as the non-neuronal cell line, C6 glioma, bound negligible amounts of toxin. Variability of immunofluorescence staining was due in part to the increase in size of N2AB-1 cells as they progress through the cell cycle as measured by cell surface densities of toxin binding and DNA levels by propidium iodide (PI) staining. When N2AB-1 cells were treated with exogenous gangliosides for 24 h, cells were induced to sprout neurites and cell growth was inhibited. Analysis of DNA histograms indicated that ganglioside treatment caused more cells to appear in G0G1 of the cell cycle than that seen for untreated controls. Upon cytometric analysis of TT binding to ganglioside treated cells, it was apparent that treatment stimulated all cells to bind TT in larger amounts per cell than that seen with untreated N2AB-1 cells. These data suggest that TT binding and, therefore, toxin receptors are constant in density throughout the cell cycle of these neuroblastoma cells and that exogenous gangliosides can cause differentiation followed by increased toxin binding.
 ...
PMID:Flow cytometric analysis of tetanus toxin binding to neuroblastoma cells. 390 30

Tetanus toxin (TT) binding to cultured rat and bovine adrenal medullary cells has been investigated using indirect immunofluorescence and anti-dopamine-beta-hydroxylase (DBH) antibodies as a probe to identify catecholaminergic cells. TT binds to all rat adrenal medullary cells which display a neuronal phenotype induced by treatment with nerve growth factor and/or medium conditioned by C6 glioma cells. In contrast, 90-95% of the rounded DBH-positive cells are TT-negative, suggesting that in vitro-transdifferentiation of rat chromaffin cells alternates the expression of membrane properties. Cultured bovine chromaffin cells have no TT binding sites independent of their morphological phenotype.
 ...
PMID:Tetanus toxin binding to different morphological phenotypes of cultured rat and bovine adrenal medullary cells. 635 5

We examined the effect of tetanus toxin on clonal neuroblastoma X glioma hybrid cells, NG108-15, by intracellular microelectrode studies of passive membrane electrical properties and action potentials generated under various conditions. Binding of tetanus toxin to the surface of the cells was demonstrated by indirect immunofluorescent staining but no morphological alteration was observed in tetanus toxin-treated cells under a phase contrast microscope. These is no significant difference between the tetanus toxin-treated and untreated cells in their passive electrical membrane properties, i.e. resting membrane potentials, input resistances, time constants and input capacities. Cells in 120 mM Na+, 2 mM Ca2+ salt solution showed Na spikes, and cells in high Ca2+ (30 mM), Na+-free salt solution showed Ca spikes in response to depolarizing current pulses. While the Na spike was not affected by tetanus toxin, the Ca spike was blocked by the toxin. The minimum dose of tetanus toxin for maximum suppression of the peak potential level of the Ca spike was 250 ng/ml. Addition of tetraethyl ammonium (TEA) to extracellular fluid enhanced the Ca spike in untreated cells. In toxin-treated cells, TEA did not alter the effect of tetanus toxin on the Ca spike. Blockade of the Ca spike by tetanus toxin could be detected even at low extracellular Ca2+ concentration (10 mM) by adding TEA to the extracellular fluid and adjusting the membrane potential to a steady hyperpolarized level (-80 mV) to ensure optimal and uniform electrical responses. The usefulness of NG108-15 hybrid cells for in vitro investigations on the mechanism of action of tetanus toxin was discussed.
 ...
PMID:Action of tetanus toxin on cholinergic neuroblastoma X glioma hybrid cells: selective blockade of Ca spikes. 637 74

Neuronotrophic factors, a class of macromolecules thought to be present within the neuronal environment are required to support the survival in vitro of peripheral neurons. In the present study we have established bioassay culture systems suitable for the identification of similar agents for intrinsic neurons of the central nervous system. The striatum, hippocampus and septum of 18 day fetal rats were dissociated and plated in a serum-free medium on a neurite conducive substratum which allows an easy recognition of neurons under phase contrast microscopy. These cultures contain predominantly neurons as assessed by tetanus toxin labelling, a well recognized neuronal marker. Seeding the cell suspensions at decreasing densities yields after 24 h a density dependent survival of the neuronal population. Thus a low seeding density could be chosen where survival of these neurons required an exogenous source of trophic factors. Survival of central neurons was promoted by several conditioned media derived from rodent glial cell cultures, both primary (astroglia, Schwann) and clonal (C6 glioma, Schwannoma). Serial dilutions of these media allowed the titration of their respective neuronotrophic activities. In addition, conditioned media derived from the central neuronal cultures themselves, when seeded at a high density, were also able to support the survival of low density seeded central neurons.
 ...
PMID:Use of central neuronal cultures for the detection of neuronotrophic agents. 637 2

Mature T cells are susceptible to activation-induced cell death in the periphery. Activation-induced cell death is thought to involve CD95/CD95 ligand interactions in vivo. Here we report that stimulated, CD45RO+ human T cell lines specific for myelin basic protein or tetanus toxoid from multiple sclerosis patients and healthy individuals resist apoptosis induced by soluble recombinant CD95 ligand in vitro. In contrast, the same CD95 ligand effectively kills Jurkat T lymphoma and human malignant glioma cells. The resistance of the T cell lines is not due to a lack of CD95 expression at the cell surface and is not overcome by coexposure to CD95 ligand and inhibitors of RNA or protein synthesis. The expression level of BCL-2 is lower in Jurkat than in Ag-specific T cells. After exposure to soluble CD95 ligand, Jurkat T cells, but not Ag-specific T cells, exhibit loss of BCL-2 and BCL-X expression whereas BAX expression is not affected. Surprisingly, Ag-specific T cells are rather sensitive to CD95 ligand expressed at the cell surface of N2A neuroblastoma cells. Accessory molecules expressed by the CD95 ligand-expressing effector cell are dispensable for apoptosis since the T cells are equally sensitive to agonistic APO-1 Ab. Further studies are required to determine whether resistance to soluble CD95 ligand-mediated apoptosis is a possible escape mechanism for T cells from peripheral deletion that may have relevance for autoimmune disorders.
 ...
PMID:Human autoreactive and foreign antigen-specific T cells resist apoptosis induced by soluble recombinant CD95 ligand. 927 96

Many inherited neurological diseases and cancers could potentially benefit from efficient targeted gene delivery to neurons of the central nervous system. The nontoxic fragment C (HC) of tetanus toxin retains the specific nerve cell binding and transport properties of tetanus holotoxin. The HC fragment has previously been used to promote the uptake of attached proteins such as horseradish peroxidase, beta-galactosidase and superoxide dismutase into neuronal cells in vitro and in vivo. We report the use of purified recombinant HC fragment produced in yeast and covalently bound to polylysine [poly(K)] to enable binding of DNA. We demonstrate that when used to transfect cells, this construct results in nonviral gene delivery and marker gene expression in vitro in N18 RE 105 cells (a neuroblastoma x glioma mouse/rat hybrid cell line) and F98 (a glioma cell line). Transfection was dependent on HC and was neuronal cell type specific. HC may prove a useful targeting ligand for future neuronal gene therapy.
 ...
PMID:Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin. 1009 62


1 2 Next >>