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)

Intact and permeabilized glioma C6 cells were incubated with [14C]serine in media containing low (100 nM) or high (2 mM) [Ca2+] and serine incorporation into phosphatidylserine was examined. In all cases thapsigargin, a blocker of the endoplasmic reticulum Ca(2+)-ATPase, diminished this process, whereas the action of the ionophore A23187 was dependent on the external calcium concentration and time of incubation. In permeabilized cells incubated at 100 nM Ca2+, serine incorporation into phosphatidylserine was diminished when the endoplasmic reticulum Ca2+ levels were lowered by the ionophore. In intact cells incubated at 2 mM CaCl2, addition of A23187 had no effect for the first 30 min and later decreased [14C]serine incorporation. This result seems to be not connected with the degradation of already formed phosphatidylserine, or with an enhanced metabolic conversion of this phospholipid, but with the decrease of its synthesis. The mechanism of this last process appears to be involved in the ionophore-induced perturbation of cellular Ca2+ homeostasis. Our results indicate that phosphatidylserine synthesis is a Ca(2+)-regulated process.
 ...
PMID:Effect of ionophore A23187 and thapsigargin on serine incorporation into phosphatidylserine in intact and permeabilized glioma C6 cells at high and low Ca2+ concentrations. 813 13

The effect of heat shock on agonist-stimulated intracellular Ca2+ mobilization and the expression of heat shock protein 72 (hsp72) in neuroblastoma x glioma hybrid cells (NG 108-15 cells) were examined. Hsp72 was expressed at 6 h after heat shock (42.5 degrees C, 2 h), reached a maximum at 12 h, and decreased thereafter. Bradykinin-induced [Ca2+]i rise was attenuated to 28% of control by heat shock at 2 h after heat shock, and reversion to the control level was seen 12 h later. When the cells were treated with quercetin or antisense oligodeoxyribonucleotide against hsp72 cDNA, the synthesis of hsp72 was not induced by heat shock, whereas bradykinin-induced [Ca2+]i rise was abolished and the [Ca2+]i rise was not restored. Recovery from this stressed condition was evident when cells were stimulated by the Ca(2+)-ATPase inhibitor thapsigargin, even in the presence of either quercetin or antisense oligodeoxyribonucleotide. Inositol 1,4,5-trisphosphate (IP3) production was not altered by heat shock at 12 h after heat shock, whereas IP3 receptor binding activity was reduced to 45.3%. In the presence of quercetin or antisense oligodeoxyribonucleotide, IP3 receptor binding activity decreased and reached 27.2% of the control 12 h after heat shock. Our working thesis is that heat shock transiently suppresses the IP3-mediated intracellular Ca2+ signal transduction system and that hsp72 is involved in the recovery of bradykinin-induced [Ca2+]i rise.
 ...
PMID:Effect of heat shock on intracellular calcium mobilization in neuroblastoma x glioma hybrid cells. 818 35

The activation of P2-purinergic receptors on C6-2B rat glioma cells caused a transient increase in cytosolic-free Ca2+ concentration ([Ca2+]i) as detected by Fura 2 fluorescence ratio imaging of single cells. These purinergic receptors are of the P2U subtype because UTP and ATP were equipotent and substantially more potent than the P2X- and P2Y-selective agonists alpha,beta-methylene ATP and 2-methylthio ATP, respectively. There was homologous desensitization of the Ca2+ responses between UTP and ATP but no heterologous desensitization between these nucleotides and another Ca(2+)-mobilizing receptor agonist, alpha-thrombin. The UTP-induced peak [Ca2+]i rise was insensitive to chelation of extracellular Ca2+ with EGTA. However, the response was abolished after either depletion of intracellular Ca2+ stores with the microsomal Ca(2+)-ATPase inhibitor thapsigargin or blockade of Ca2+ release from intracellular stores with the muscle relaxant dantrolene. The activation of P2U-purinergic receptors and thrombin receptors increased the formation of total inositol phosphates (IPs) and inhibited cAMP accumulation elicited with either the beta-adrenergic receptor agonist (-)-isoproterenol, or forskolin, a direct activator of adenylyl cyclase. UTP- and alpha-thrombin-induced changes in the levels of IPs, cytosolic Ca2+, and agonist-elicited cAMP accumulation were dramatically inhibited (> 80%) by acute treatment of the cells with the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate but not with the inactive ester 4 alpha-phorbol 12,13-didecanoate. We conclude that in C6-2B cells, the increase in [Ca2+]i after activation of P2U-purinergic receptors is primarily a result of IPs-mediated release of Ca2+ from intracellular stores with secondary influx of Ca2+ by capacitative mechanisms. Also, the inhibition by UTP and alpha-thrombin of agonist-elicited cAMP accumulation is mediated through an increase in [Ca2+]i.
 ...
PMID:P2U-purinergic receptors on C6-2B rat glioma cells: modulation of cytosolic Ca2+ and cAMP levels by protein kinase C. 826 55

In C6-2B rat glioma cells, agonist-stimulated cAMP accumulation is potently inhibited after the stimulation of endogenous bradykinin receptors or stably transfected substance K receptors, coupled to phosphatidylinositol hydrolysis. In the present report, pharmacological tools were used to selectively stimulate either protein kinase C or Ca2+, the two final effectors activated upon phosphatidylinositol hydrolysis, and their role in the inhibition of the C6-2B cell cAMP signaling pathway was investigated. Activation of protein kinase C by an acute treatment with phorbol 12-myristate 13-acetate or L-alpha-1-oleoyl-2-acetyl-sn-3-glycerol did not reduce, but rather enhanced, the cAMP accumulation elicited by forskolin, a direct activator of adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. This effect was antagonized by the protein kinase inhibitor H-7 and mimicked by the protein phosphatase inhibitor okadaic acid. Thapsigargin, a selective microsomal Ca(2+)-ATPase inhibitor, evoked a sustained increase in the intracellular free Ca2+ concentration, with an EC50 of 24.8 +/- 4.3 nM, and inhibited the cAMP accumulation induced by the beta-adrenergic receptor agonist isoproterenol with comparable potency (IC50 = 19.3 +/- 0.2 nM), strongly suggesting a causal relationship between the two phenomena. The inhibition by thapsigargin of isoproterenol- or forskolin-stimulated cAMP accumulation was not affected by pertussis toxin or down-regulation or inhibition of protein kinase C. Dantrolene, a blocker of Ca2+ release from intracellular stores, antagonized 1) the Ca2+ transient in response to thapsigargin and substance K and 2) the inhibitory effect of these compounds on isoproterenol- or forskolin-induced cAMP accumulation. Moreover, sequestration of intracellular Ca2+ with the cell-permeable Ca2+ chelator ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester abolished the cAMP inhibition mediated by thapsigargin. Finally, isoproterenol- or forskolin-stimulated adenylyl cyclase activity in digitonin-permeabilized cells was not affected by either thapsigargin or substance K. These data provide compelling evidence that increases in intracellular free Ca2+ concentration without activation of protein kinase C suffice and are responsible for the inhibition of cAMP accumulation in C6-2B cells.
 ...
PMID:Ca2+ inhibition of beta-adrenergic receptor- and forskolin-stimulated cAMP accumulation in C6-2B rat glioma cells is independent of protein kinase C. 838 3

The temporal and spatial changes of intracellular free calcium ([Ca2+]i) within the cytosol and nucleis of C6 glioma cells have been investigated with laser confocal scanning microscopy to evaluate the current view that Ca2+ ions pass freely through nuclear pores by diffusion. Our results indicate that localized cytosolic Ca2+ release, which appeared as puffs, spread with an apparent diffusion rate of 0.35 +/- 0.07 microns/sec (n = 44). This release was followed by an immediate Ca2+ uptake at the resting stage. Following the treatment with thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase, release of nuclear Ca2+ from certain nuclear hot zones and nuclear envelope was obtained. Most of the nuclear Ca2+ released were confined to the nuclear boundary, but a slow migration of Ca2+ towards the cytosol was observed. The apparent diffusion rate of this Ca2+ release is 0.015 microns/sec. By contrast, the inward spread into nucleus occurred with a diffusion rate of 0.04 microns/sec. From these diffusion rates and other experimental evidence, we conclude that the movement of Ca2+ at the nucleocytosolic interface is more than a simple diffusion process and the interface is a barrier to Ca2+ movement.
 ...
PMID:Nuclear envelope acts as a calcium barrier in C6 glioma cells. 856 1

We examined the effects of tetrandrine (TET) on Ca2+ mobilization in various types of cells using inositol trisphosphate-generating drugs and compared it with those using the microsomal Ca(2+)-ATPase inhibitor thapsigargin (TG) which is a tool for analyzing Ca2+ store-regulated Ca2+ entry (capacitative Ca2+ entry). In rat pheochromocytoma PC12 cells, 100 microM TET abolished high K+ (30 mM)-induced sustained increase in [Ca2+]i and partially inhibited bradykinin (1 microM)-induced or TG (100 nM)-induced Ca2+ entry. In NIH/3T3 fibroblasts, 100 microM TET abolished Ca2+ entry induced by bombesin (1 microM) or TG (100 nM). In rat glioma C6 cells, the addition of 100 microM TET reduced the sustained elevation of [Ca2+]i induced by endothelin 1 (10 nM) or TG (100 nM) declining to the resting level. In rat parotid acinar cells, 100 microM TET abolished a sustained increase in [Ca2+]i induced by carbachol (100 microM) or TG (100 nM). In human leukemia T-cell line Jurkat, 100 microM TET did not inhibit Ca2+ entry evoked by the anti-CD3 antibody OKT3 (10 micrograms/ml) or TG (100 nM). The present results suggest that the action of TET on Ca2+ entry is dependent on cell types.
 ...
PMID:Calcium antagonistic actions of tetrandrine depend on cell types. 858 49

Long-term superfusion with bradykinin causes oscillations of cytosolic Ca2+ activity ([Ca2+]i) in Fura-2 loaded rat glioma cells. The [Ca2+]i rise is associated with synchronous plasma membrane hyperpolarization oscillating with a frequency of 0.8-1.8 per min. The initial large transient [Ca2+]i rise, induced immediately with bradykinin admission results from InsP3-mediated Ca2+ release, whereas the subsequent oscillations depend mainly on Ca2+ influx, as demonstrated: (i) by blockade of [Ca2+]i oscillations by reduction of [Ca2+]ex' or addition of Ca(2+)-channel blockers; and (ii) evidence from Mn2+ quench experiments. Suppression of [Ca2+]i oscillations with high K+ depolarization and with block of Ca(2+)-dependent K+ channels proves that membrane hyperpolarization is required for Ca2+ influx during the oscillation. Ca2+ release from intracellular stores by inhibitors of endoplasmic reticulum Ca(2+)-ATPase attenuates or blocks the [Ca2+]i oscillations. This suggests that bradykinin-induced Ca2+ influx is controlled by the filling state of the stores. The [Ca2+]i oscillations are suppressed by hypertonic medium and enhanced by hypotonic medium. Cell swelling enhances Ca2+ influx. We propose the following model for generation of the oscillations in the glial cell line: InsP3-induced Ca2+ release from internal stores periodically evokes Ca2+ influx through Ca(2+)-permeable cation channels. Hyperpolarization of the plasma membrane due to the activation of Ca(2+)-dependent K+ channels enhances the Ca2+ influx. The concomitant K+ efflux could lead to cell shrinkage which suppresses Ca2+ influx. Cell volume and membrane potential probably serve as feedback regulators during the [Ca2+]i oscillations.
 ...
PMID:[Ca2+]i oscillations induced by bradykinin in rat glioma cells associated with Ca2+ store-dependent Ca2+ influx are controlled by cell volume and by membrane potential. 868 72

The effects of 2,5-di-tert-butylhydroquinone (DBHQ) and thimerosal on phosphatidylserine synthesis by the base exchange reaction and on calcium mobilization in intact glioma C6 cells were compared with that of thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca(2+)-ATPase. It has been found that all these agents inhibit phosphatidylserine synthesis by 70%, but their effectiveness are different. The data show that this inhibition is caused by Ca2+ depletion of the endoplasmic reticulum, indicating that phosphatidylserine synthesis requires high concentration of Ca2+ within this structure. On this basis and on literature data, a new model for the localization of the serine base exchange enzyme in the endoplasmic reticulum membrane is proposed.
 ...
PMID:Phosphatidylserine synthesis in glioma C6 cells is inhibited by Ca2+ depletion from the endoplasmic reticulum: effects of 2,5-di-tert-butylhydroquinone and thimerosal. 871 2

Transcription mechanisms regulating nerve growth factor (NGF) gene expression in the CNS are yet to be thoroughly understood. We have used C6-2B rat glioma cells to characterize the signal transduction pathways that contribute to transcriptional and posttranscriptional regulation of NGF mRNA. Because the NGF promoter contains an AP-1 consensus sequence, we have investigated whether increases in AP-1 binding activity correlate with enhanced NGF mRNA expression. Gel mobility shift assays using an oligonucleotide homologous to the AP-1 responsive element of the rat NGF gene (AP-1NGF) revealed that 12-O-tetradecanoyl phorbol-13-acetate (TPA) and, to a lesser extent, isoproterenol (ISO) and thapsigargin, a microsomal Ca(2+)-ATPase inhibitor, stimulated binding to AP-1NGF within 2 h. All of these stimuli increased NGF mRNA levels within 3 h. Cycloheximide pretreatment blocked the TPA and ISO-mediated binding to AP-1NGF suggesting that de novo synthesis of c-Fos/c-Jun may be required for the transcriptional regulation of NGF gene. Nuclear run-on assays and NGF mRNA decay studies revealed that TPA increases NGF transcription whereas ISO affects both transcription and mRNA stabilization. We propose that (i) different signal transduction mechanisms regulate the expression of the NGF gene in cells derived from the CNS, and (ii) both mRNA transcription and stability account for the cAMP-mediated increase in NGF mRNA levels.
 ...
PMID:Correlation between increased AP-1NGF binding activity and induction of nerve growth factor transcription by multiple signal transduction pathways in C6-2B glioma cells. 871 34

Following mobilization with the inositol 1,4,5-trisphosphate (IP3)-generating agonist bradykinin, Ca2+ stores in neuroblastoma x glioma hybrid, NG108-15 cells require extracellular Ca2+ to refill. The process by which this store refills with Ca2+ was characterized by recording bradykinin-induced intracellular free Ca2+ concentration transients as an index of the degree of refilling of the store. Cyclopiazonic acid, a microsomal Ca2+ ATPase inhibitor, reversibly depleted intracellular Ca2+ stores in these cells, but did not recruit detectable Ca2+ influx, suggesting that these cells lack substantial capacitative Ca2+ entry. The paucity of voltage-sensitive Ca2+ channels in undifferentiated NG108-15 cells, suggested that a channel analogous to that proposed to mediate capacitative Ca2+ entry in nonexcitable cells might assist refilling IP3-sensitive Ca2+ stores in these cells. The possibility that compounds shown previously to inhibit capacitative Ca2+ entry in nonexcitable cells might inhibit the refilling of the IP3-sensitive store in NG108-15 cells was explored. The IP3-sensitive store was depleted by exposure to bradykinin, allowed to refill briefly in the presence of the test compound and then challenged again with bradykinin to evaluate the degree of refilling of the store. The imidazole derivatives, econazole (10 microM), L-651582 (10 microM) and SKF 96365 (20 microM), all completely blocked the bradykinin-induced Ca2+ response. Calmodulin antagonists, W-7 (100 microM) and trifluoperazine (10 microM), were also effective, although at concentrations well above those required to inhibit calmodulin. Because of the high concentrations required to inhibit bradykinin responses, the possibility that these agents might have additional effects was explored. Compounds were tested in a paradigm in which the store was preloaded with Ca2+ before treatment. All of these agents depleted, at least partially, the preloaded store. Econazole was the least effective of the compounds tested for releasing stores, although it was comparable to the other compounds for inhibition of refilling. Although NG108-15 cells refill intracellular Ca2+ stores by a plasmalemmal Ca2+ leak, this leak shares a pharmacology similar to the capacitative Ca2+ entry pathway described for nonexcitable cells.
 ...
PMID:Pharmacologic characterization of refilling inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in NG108-15 cells. 875 Sep 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>