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)

In permeabilized C6 glioma cells and NIH 3T3 cells, the peptide endothelin 1 (ET-1) in combination with GTP gamma S stimulates the formation of inositol phosphates. In the presence of 10 microM GTP gamma S, ET-1 induces the formation of inositol phosphates with an EC50 value of 2.5 nM for C6 glioma cells and 1.6 nM for NIH 3T3 cells. The analogous peptide endothelin 3 (ET-3) is less potent than ET-1 in such action. In NIH 3T3 cells, ET-1+GTP gamma S-induced formation of inositol phosphates could be detected after 1 min of stimulation, and it increased for up to 30 min. ET-1-induced effects were partially reduced by pretreatment of the cells with pertussis toxin (1 microgram/ml) in C6 glioma cells, but were unaffected in NIH 3T3 cells. In binding studies in whole C6 cells and NIH 3T3 cells, specific binding for [125I]ET-1 was detected. Cross-linking of [125I]ET-1 in whole C6 cells revealed the presence of two binding proteins for ET-1 of 74 kDa and 55 kDa. ET-1 at 100 nM inhibited the labeling of both proteins by [125I]ET-1. However, ET-3 inhibited the labeling of the 55 kDa protein only. The results provide direct evidence for endothelin receptor coupling to phospholipase C through guanine nucleotide binding (G) proteins. In addition, in C6 cells, endothelin-mediated phospholipase C activation is partially inhibited by pertussis toxin pretreatment. The endothelin receptor involved in phospholipase C stimulation in C6 cells seems to correspond to a 74 kDa protein which binds ET-1 but not ET-3.
 ...
PMID:Endothelin-elicited stimulation of phospholipase C is mediated by guanine nucleotide binding protein(s). 132 77

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.
 ...
PMID:Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. 165 Apr 80

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.
 ...
PMID:Comparison of endothelin binding and calcium mobilization in C6-BU-1 rat glioma and N18TG2 mouse neuroblastoma cells. 165 31

Endothelin (ET)-related peptides robustly stimulated [3H]-inositol phosphate (IP) formation in cultured cerebellar granule cells, astrocytes, and C6 glioma cells. Their agonist selectivities were ET-1 = ET-2 greater than or equal to sarafotoxin S6b greater than ET-3 greater than big ET-1 for granule cells and ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for cerebellar astrocytes and C6 glioma cells. These effects were Ca(2+)-dependent but insensitive to antagonists of L-type Ca2+ channels and the Na+/Ca2+ antiporter. Pretreatment of cells with ET-1 or S6b induced homologous desensitization of phosphoinositide (PI) response mediated by ET receptors. Long-term pertussis toxin (PTX) treatment attenuated the phosphoinositide (PI) response in astrocytes and glioma but not in granule cells. ET-1 and its related peptides increased [Ca2+]i in C6 glioma by two distinct pathways: IP3-induced Ca2+ mobilization or receptor-operated Ca2+ influx. La3+, Mn2+, and Cd2+ inhibited the Ca2+ influx and sustained PI turnover, while Ca2+ mobilization was attenuated by phorbol ester and TMB-8. ET-induced Ca2+ influx was essential for the sustained [Ca2+]i increase and PI turnover. Homologous desensitization of [Ca2+]i increase was also noted. In cerebellar granule cells, ET evoked the release of [3H]D-aspartate from these neurons. This action appears to be dependent on PI hydrolysis and [Ca2+]i increase and modulated by protein kinase C.
 ...
PMID:Endothelin-induced activation of phosphoinositide turnover, calcium mobilization, and transmitter release in cultured neurons and neurally related cell types. 172 40

Endothelin (ET)-mediated Ca++ signaling in NG108-15 neuroblastoma x glioma cells was studied by measuring free intracellular Ca++ (Ca++i) levels with the fluorescent Ca++ indicator, fura-2. ET-1 produced biphasic increases in Ca++i consisting of a transient peak elevation followed by a sustained plateau phase. Both peak and plateau Ca++i responses to 5 nM ET-1 were reduced by depletion of extracellular Ca++. Peak responses were also attenuated by inhibitors of inositol phosphate metabolism, whereas plateau responses were affected by dihydropyridine Ca++ channel agonists and antagonists and by differentiation. These results suggest that peak Ca++i responses to ET-1 involve mobilization of Ca++ from inositol phosphate-sensitive intracellular stores and influx of extracellular Ca++ through nonclassical Ca++ channels, whereas plateau responses are mediated by Ca++ influx through dihydropyridine-sensitive, voltage-gated channels.
 ...
PMID:Endothelin and calcium signaling in NG108-15 neuroblastoma x glioma cells. 186 55

Effects of endothelin (ET) homologues (ET-1, 2, 3 and sarafotoxin S6b) and its precursor (big ET-1) on phosphoinositide (PI) turnover were compared in neurally-related cell cultures. All ET-related peptides induced a robust increase of PI turnover in cerebellar astrocytes, C6-glioma and cerebellar granule cells. The rank order of potency in stimulating PI turnover was ET-1 = ET-2 greater than or equal to S6b greater than ET-3 greater than big ET-1 for granule cell neurons, while it was ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for astrocytes and C6-glioma cells. Short-term pretreatment with phorbol dibutyrate (PDBu) attenuated the ET-1-induced PI response in all three types of cultures. However, long-term pretreatment with PDBu attenuated the response in granule cells and C6-gliomas, but enhanced responses to ET and ATP in astrocytes. Long-term exposure of cells to pertussis toxin (PTX) attenuated the PI response to ET in astrocytes and C6-gliomas, but not in granule cells. Thus, phospholipase C-coupled ET receptors are expressed in both neurons and glial cells, but they differ considerably in their pharmacological selectivity and signal transduction mechanisms in stimulating PI hydrolysis.
 ...
PMID:Comparative studies of phosphoinositide hydrolysis induced by endothelin-related peptides in cultured cerebellar astrocytes, C6-glioma and cerebellar granule cells. 215 94

A series of C-terminal linear endothelin analogues were prepared and their activities in C6 rat glioma cell line were tested. Among the synthetic analogues, IBDP 064, Fmoc-Leu-Asp-Ile-Ile-Trp-OH, was the most potent and selective inhibitor of endothelin-3-induced cell proliferation. Its action was comparable with that of the previously described peptide IRL 1038, [Cys11-Cys15]-ET-1(11-21), an ETB specific inhibitor.
 ...
PMID:A new endothelin C-terminal analogue IBDP 064 antagonizes endothelin-3-induced cell proliferation. 765 97

The effects of Ca2+ on the translocation of conventional and new protein kinase C isozymes in intact cells were studied by using C6 glioma cells as a model system. Two conditions which monitor intracellular Ca2+ were performed: one is extracellular Ca(2+)-depletion by treating the cells with physiological saline solution (PSS) without Ca2+ but containing 0.5 mM EGTA, the other is treating the cells with 1 microM ionomycin to induce Ca(2+)-influx. In addition, the TPA and endothelin-1 induced translocations of conventional and new PKC isozymes under these two conditions were also comparatively studied. When the intact cells were treated with Ca(2+)-free, EGTA containing PSS, the membrane-bound conventional PKC alpha (cPKC alpha) was greatly reduced and cytosolic cPKC alpha was slightly increased. However, neither membrane bound nor cytosolic new PKC delta (nPKC delta) was affected by extracellular Ca(2+)-depletion. On the other hand, when the cells were treated with 1 microM ionomycin, the translocation of cPKC alpha itself was observed while nPKC delta was not affected. In extracellular Ca(2+)-depletion, the translocation of cPKC alpha induced by 100 nM TPA still occurred although the extent of translocation was smaller than that induced by TPA under normal Ca2+ conditions; however, that induced by 30 nM ET-1 was blocked. After the cells were treated with 1 microM ionomycin, the translocation of cPKC alpha induced by 30 nM TPA was further increased compared to 1 microM ionomycin or 30 nM TPA alone, while that induced by ET-1 was only slightly further increased. All these results suggested that in intact cells, the activation of cPKC alpha was operated by both the intracellular Ca2+ level and diacylglycerol and that of nPKC delta was operated by diacylglycerol alone as predicted by their properties from purified enzyme or cDNA. In addition, the translocation of cPKC alpha induced by the natural activator ET-1 seemed to be more dependent on Ca2+ than TPA in intact cells.
 ...
PMID:Effects of Ca2+ on the activation of conventional and new PKC isozymes and on TPA and endothelin-1 induced translocations of these isozymes in intact cells. 802 77

The mitogenic action of endothelins (ETs) 1 and 3 was studied on C6 rat glioma cells in serum-free culture conditions. In order to characterize the ET receptor subtype involved in this effect, BQ-123, and ETA receptor selective antagonist was used. Our results confirmed that both ET-1 and ET-3 are mitogenic peptides for C6 cells and demonstrated for the first time that the ETA receptor antagonist BQ-123 inhibits the proliferative effect of both ET-1 and ET-3 in this cellular system, providing evidence of an atypical ET receptor on C6 cells.
 ...
PMID:BQ-123 inhibits both endothelin 1 and endothelin 3 mediated C6 rat glioma cell proliferation suggesting an atypical endothelin receptor. 813 46

Addition of endothelins (ETs) to neuroblastoma-glioma hybrid cells (NG108-15) induced increases in cytosolic free Ca2+ ([Ca2+]i) levels of labeled inositol monophosphates and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The increases in [Ca2+]i elicited by the three ETs (ET-1, ET-2, and ET-3) were transient and did not show a sustained phase. Chelating extracellular Ca2+ in the medium by adding excess EGTA decreased the ET-mediated Ca2+ response by 40-50%. This result indicates that a substantial portion of the increase in [Ca2+]i was due to influx from an extracellular source. However, the increase in [Ca2+]i was not affected by verapamil or nifedipine (10(-5) M). A rank order potency of ET-1 > ET-2 > ET-3 is shown for the stimulated increase in [Ca2+]i, as well as labeled inositol phosphates, in these cells. ATP (10(-4) M) and bradykinin (10(-7) M) also induced the increases in [Ca2+]i and Ins(1,4,5)P3 in NG108-15 cells, albeit to a different extent. When compared at 10(-7) M, bradykinin elicited a five- to sixfold higher increase in the level of Ins(1,4,5)P3, but less than a twofold higher increase in [Ca2+]i than those induced by ET-1. Additive increases in both Ins(1,4,5)P3 and [Ca2+]i were observed when ET-1, ATP, and bradykinin were added to the cells in different combinations, suggesting that each receptor agonist is responsible for the hydrolysis of a pool of polyphosphoinositide within the membrane. ET-1 exhibited homologous desensitization of the Ca2+ response, but partial heterologous desensitization to the Ca2+ response elicited by ATP. On the contrary, ET-1 did not desensitize the response elicited by bradykinin, although bradykinin exhibited complete heterologous desensitization to the response elicited by ET-1. Taken together, these results illustrate that, in NG108-15 cells, a considerable amount of receptor cross talk occurs between ET and other receptors that transmit signals through the polyphosphoinositide pathway.
 ...
PMID:Endothelin-mediated calcium response and inositol 1,4,5-trisphosphate release in neuroblastoma-glioma hybrid cells (NG108-15): cross talk with ATP and bradykinin. 838 Apr 32


1 2 Next >>