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

The morphological and biochemical changes that occur during chemical hypoxic injury in a neural cell line were studied in the presence and absence of calcium. Oligodendroglial-glioma hybrid cells (ROC-1) were subjected to inhibitors of glycolytic and oxidative ATP synthesis (chemical hypoxia). Complete respiratory inhibition depleted [ATP] to less than 5% of control by 4 min. Blebs appeared on the cell surfaces and cells began to swell within a few minutes of ATP depletion. A 200% increase in cell volume and bleb coalescence preceded irreversible cell injury (lactate dehydrogenase release) which began at approximately 20 min with 50% cell death by 40 min. In energized cells an equivalent degree of osmotic swelling induced by ouabain inhibition of the Na+, K(+)-ATPase pump did not produce blebbing or cell death. Partial inhibition of respiration decreased [ATP] to approximately 10% of control by 40 min. Blebbing and swelling began at 40 min and bleb coalescence preceded plasma membrane disruption which began at approximately 55 min. ATP depletion, blebbing, swelling, and death followed similar time courses in the presence or absence of extracellular calcium ([Ca2+]e). Intracellular calcium ([Ca2+]i) was measured using fura-2. In calcium-containing medium metabolic inhibition caused a transient increase in resting [Ca2+]i (100 +/- 17 nM) followed by a low steady-state level preceding plasma membrane disruption. Following deenergization in calcium-free medium, [Ca2+]i remained below 60 nM throughout injury and death. These data suggest that decreased ATP initiates a sequence of events including bleb formation and cell swelling that lead to irreversible cell injury in the absence of large increases in [Ca2+]i.
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PMID:Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1). 161 11

Endothelin 1 causes a strong Ca2+ signal in C6 rat glioma cells as measured by fura-2 fluorescence. This endothelin 1-induced Ca2+ signal was not observed when the cells were persistently infected with a measles virus strain of subacute sclerosing panencephalitis (SSPE, strain Lec). Binding of 125I-labeled endothelin 1 to the C6/SSPE cells was less than 5% of the binding to the C6 control cells, suggesting that the impairment in signal transduction was due to a loss of binding sites for endothelin 1. Treatment of the C6/SSPE cells with measles antiserum resulted in the loss of expression of viral proteins located in the membrane as well as inside the cells (antigenic modulation), but it restored neither the endothelin 1-induced Ca2+ rise nor the 125I-endothelin 1 binding. Cocultivation of uninfected C6 cells with C6/SSPE cells (9:1 ratio) resulting in contact-mediated transmission of measles virus showed that the 125I-endothelin 1 binding activity was gradually lost as a consequence of persistent virus infection.
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PMID:Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. 165 Apr 80

Ras (p21) proteins are involved in the control of cell growth and differentiation, but the mechanism by which they exert these effects is not yet known. Here we present evidence that c-Ha-ras (p21(Gly-12)) and its oncogenic mutant T24-ras (p21(Val-12)) selectively induce omega-conotoxin and dihydropyridine-sensitive Ca2+ currents within a few hours after introduction into the cytoplasm of neuroblastoma x glioma hybrid cells. Whereas control cells exhibited a mean Ca2+ current of 250 pA, it amounted to 730 pA in cells pretreated with ras protein. In cells loaded with p21(Gly-12), the effect occurred after 2 hours and was terminated after 8 hours. In contrast, introduction of p21(Val-12) resulted in a prolonged delay (6 hours) of the effect which lasted for more than 24 hours. When ras proteins were preactivated with the non-hydrolysable GTP analog GppNHp, the time courses of both p21(Gly-12) and p21(Val-12) effects were fast and sustained, suggesting that in intact cells (i) the GDP/GTP exchange is faster for p21(Gly-12) compared to p21(Val-12) and (ii) inactivation of p21(Gly-12) is mediated by GAP-induced GTPase activity. T-type Ca2+ currents and K+ currents were unaffected by ras proteins.
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PMID:Ras proteins activate calcium channels in neuronal cells. 165 68

We have previously reported that endothelin (RT) receptor activation increases intracellular calcium concentrations ([Ca2+]i) in NG108-15 cells, a hybrid of rat glioma C6-BU-1 and mouse neuroblastoma N18TG2 cells. This study was designed to further explore the origin of the ET receptor and [Ca2+]i mobilization in the parent cell lines hybridized to form the NG108-15 cells. [125I]ET-1 bound to a single class of high affinity sites in C6-BU-1 cells with a KD value of 108pM and Bmax of 12,400 sites/cell. ET-1, ET-2, ET-3 and big ET inhibited [125I]ET-1 binding to C6-BU-1 cells with KD values of 0.074, 0.167, 261 and 187 nM, respectively. All ETs produced a rapid increase in [Ca2+]i in C6-Bu-1 cells. EC50 values for ET-1, ET-2, ET-3 and big ET were 0.71, 1.14, 120 and 243 nM respectively. There was a significant correlation between the KD values obtained from competition binding experiments and the EC50 values from [Ca2+]i response curves in C6-BU-1 cells (r = 0.996, p less than 0.004). Ten nM ET-1 produced about 85% of the maximal [Ca2+]i increase in C6-BU-1 cells which was reduced by 96% in the absence of extracellular calcium. Furthermore, diltiazem (10 microM) and nifedipine (1 microM) failed to block ET-induced [Ca2+]i mobilization. None of the ETs elevated [Ca2+]i or displayed any specific [125I]ET-1 binding in N18TG2 cells. These data suggest that ET binds to a specific ET receptor in C6-BU-1 cells, and elevates [Ca2+]i through dihydropyridine-insensitive, receptor-mediated calcium influx. Further, the ability of ETs to elevate [Ca2+]i in NG108-15 hybrid cells is due to the ET receptor inherent to the C6-BU-1 glioma parent line.
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PMID:Comparison of endothelin binding and calcium mobilization in C6-BU-1 rat glioma and N18TG2 mouse neuroblastoma cells. 165 31

A significant fraction of differentiated NG108-15 neuroblastoma/glioma cells have Ca2+ channel current different from that of undifferentiated cells. In the former cells, the Ca2+ channel sensitive to omega-conotoxin GVIA had slowed activation kinetics and was facilitated by depolarizing prepulses. These kinetic features are identical to those produced by inhibition of the channel by G proteins. Prolonged treatment with prostaglandin E1 and theophylline, agents that cause cellular differentiation, promoted incidence and extent of the tonic inhibition. Intracellular guanosine 5'-[beta-thio]diphosphate removed the tonic inhibition, suggesting sustained activation of a G protein, but pertussis toxin did not block it. A sulfhydryl alkylating agent, N-ethylmaleimide (0.1 mM), rapidly eliminated agonist-induced inhibition, whereas N-ethylmaleimide spared the tonic inhibition and the one induced by intracellular guanosine 5'-[gamma-thio]triphosphate. An agonist could further inhibit the Ca2+ channel that was already tonically inhibited. After washout of an inhibitory agonist, the tonic inhibition was temporarily removed. This "rebound facilitation" gradually faded within a few minutes. Pertussis toxin or N-ethylmaleimide prevented the rebound facilitation, whereas phorbol ester, forskolin, or arachidonic acid induced neither the rebound facilitation nor the tonic inhibition. Whatever its mechanism, the tonic inhibition of Ca2+ channels may serve as the basis for long-term and bidirectional regulation of activity of neuronal Ca2+ channels.
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PMID:Tonic inhibition and rebound facilitation of a neuronal calcium channel by a GTP-binding protein. 165 56

Previous reports have provided conflicting evidence as to whether the response to TRH desensitizes. Here we show that TRH stimulation of phosphoinositide (PPI) hydrolysis, measured as inositol phosphate accumulation in the presence of LiCl, desensitizes in rat pituitary GH3 cells and in rat glioma C6 cells stably transfected with mouse pituitary TRH receptor complementary DNA. In GH3 cells, the rate of stimulation by 1000 nM TRH of PPI hydrolysis was maximal initially and then decreased by 44 +/- 13% after 20 min. In an experimental paradigm in which PPI hydrolysis was measured by adding 20 mM LiCl at different times after TRH, desensitizations caused by 3, 10, and 1000 nM TRH were 33 +/- 5%, 41 +/- 6%, and 69 +/- 2%, respectively. In transfected C6 cells, TRH-induced desensitization of 76 +/- 9% was found. In GH3 cells, 1 microM phorbol myristate acetate (PMA), an activator of protein kinase C, inhibited the initial response to TRH by 75 +/- 6% and preexposure to PMA and TRH decreased the rate of PPI hydrolysis by 98 +/- 1% after 60 min. One hundred micromolar H-7 (1-(5-isoquinolinesulfonyl)-2-methyl piperazine), an inhibitor of protein kinases, abolished the effect of PMA but did not inhibit TRH-induced desensitization. Elevation of cytoplasmic free Ca2+ by K+ depolarization increased TRH stimulation of PPI hydrolysis. We conclude that TRH stimulation of PPI hydrolysis acutely desensitizes and that this effect is not specific to pituitary cells. TRH-induced desensitization, moreover, does not appear to be mediated by protein kinase C or by elevation of cytoplasmic free Ca2+.
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PMID:Thyrotropin-releasing hormone stimulation of phosphoinositide hydrolysis desensitizes. Evidence against mediation by protein kinase C or calcium. 165 82

Calcium ion (Ca2+) is considered to be involved in the regulation of numerous cellular processes. CaM kinase II is present at the highest concentration in the brain and is considered to be involved in the regulation and coordination of numerous cellular processes. CaM kinase II is activated by Ca2+/calmodulin and simultaneously undergoes autophosphorylation. It has not been determined whether the enzyme is activated in the cell systems in response to the increase in cytoplasmic Ca2+ concentration. We have studied CaM kinase II in several kinds of cells including the primary cultures of cerebellar granule cells and the cell lines of rat embryo fibroblast 3Y1 cells, neuroblastoma cells, PC12 cells and C6 glioma cells. The immunohistochemical analysis demonstrated the presence of CaM kinase II in all of the cells examined. Furthermore, the kinase in cerebellar granule cells was activated by the stimulation of the glutamic acid receptor. Autophosphorylation of CaM kinase II in 3Y1 cells was stimulated by the addition of growth factors. These results suggest that CaM kinase II undergoes activation and autophosphorylation in response to various stimuli to the cells and is regulated in the dynamic state.
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PMID:[Regulation of Ca2+/calmodulin-dependent protein kinase II in the cell systems in response to cellular stimuli]. 166 Apr 42

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.
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PMID:L- and T-type calcium channels in cultured neuronal cell lines are insensitive to tetanus toxin. 166 81

Maitotoxin (MTX) and the analogues, bis-desulfated-MTX (didesulfo-MTX), mono-desulfated-MTX (monodesulfo-MTX), and hydrogenated-MTX (H-MTX) were examined on 45Ca2+ influx and phosphoinositide breakdown with hamster insulinoma HIT cells and rat glioma C6 cells. The activity of MTX was greatly reduced either by desulfation or by hydrogenation. Didesulfo-MTX weakly stimulated calcium influx in HIT cells, but had no stimulatory effect on either calcium influx or phosphoinositide breakdown in C6 cells. All the analogues inhibited MTX-induced calcium influx in either HIT or C6 cells. Didesulfo-MTX inhibited the calcium influx elicited by 3 ng/ml MTX in C6 cells with an IC50 of 7.0 +/- 0.7 ng/ml. The data suggest that the sulfate groups in MTX are important for stimulation of calcium influx and phosphoinositide breakdown, but are not essential for binding to a receptor-site on cell membranes. Although catalytic reduction of double bonds in MTX reduced activity by nearly 100-fold, a tritiated H-MTX still represents a potential radioligand for identification of MTX-binding sites.
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PMID:Effect of maitotoxin analogues on calcium influx and phosphoinositide breakdown in cultured cells. 166 3

1. The second-messengers system of bradykinin (BK) receptors was examined in NG108-15 neuroblastoma x glioma hybrid cells. 2. An application of BK induced an immediate outward (K+) current and acetylcholine (ACh) release, which are generated through inositol 1,4,5-trisphosphate (InsP3)-dependent Ca2+ ions. 3. Application of phorbol dibutyrate (a protein kinase C activator) produced a voltage-dependent inward current and inhibited another K+ (M)-current. 4. A similar current response has been produced by ACh in NG108-15 cells transfected with rodent muscarinic ACh receptor I and III subtype genes. 5. These results suggest a dual and time-dependent role for these two intracellular messengers in the control of neuronal signalling by BK and ACh.
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PMID:Phosphoinositides and synaptic function in NG108-15 neuroblastoma x glioma hybrid cells. 167 6


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