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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Regulation of cholecystokinin (CCK) and the proto-oncogene c-fos mRNA expression was studied in the human neuroblastoma cell line SK-N-MC. Cells were treated either with the tumor promoting phorbol-ester phorbol-12-myristate-13-acetate (PMA), the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), which results in an elevated intracellular cyclic AMP (cAMP) level, or with a combination of PMA and IBMX. The level of CCK and c-fos mRNA was determined by Northern-blot analysis with CCK and c-fos specific antisense RNA probes after 4-24 h of drug treatment. Treatment with PMA and IBMX for 4-24 hours transiently raised the CCK mRNA level approximately 1.5-3.5 times compared to the controls, and the combination PMA and IBMX had an additive effect and elevated CCK mRNA abundance 1.5-6.5 times. Under the same experimental conditions, both PMA and IBMX elevated the c-fos mRNA level approximately 3-5.5 times. The drug combination showed a pronounced synergistic effect and raised the c-fos mRNA level approximately 3-20 times as compared to controls. Apparently, CCK and c-fos mRNA expression appears to be regulated by similar protein kinase C (PKC) and cAMP-dependent mechanisms in SK-N-MC cells.
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PMID:Phorbol 12-myristate-13-acetate (PMA) stimulates a differential expression of cholecystokinin (CCK) and c-fos mRNA in a human neuroblastoma cell line. 172 Apr 2

Exposure to ethanol for several days increases the number and function of dihydropyridine-sensitive Ca2+ channels in excitable tissues. In the neural cell line PC12, this process is blocked by inhibitors of protein kinase C (PKC), suggesting that PKC mediates ethanol-induced increases in Ca2+ channels. We report that treatment with 25-200 mM ethanol for 2-8 days increased PKC activity in PC12 cells and NG108-15 neuroblastoma-glioma cells. Detailed studies in PC12 cells showed that ethanol also increased phorbol ester binding and immunoreactivity to PKC delta and PKC epsilon. These changes were associated with increased PKC-mediated phosphorylation. Ethanol did not activate the enzyme directly, nor did ethanol increase levels of diacylglycerol. Ethanol-induced increases in PKC levels may promote up-regulation of Ca2+ channels, and may also regulate the expression and function of other proteins involved in cellular adaptation to ethanol.
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PMID:Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells. 174 36

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.
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PMID:Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C activity in NG-108 cells. 181 11

In neuroblastoma, amplification of the N-myc gene is closely correlated with increased metastatic ability. The mechanism by which N-myc acts to increase neuroblastoma malignancy is poorly understood as yet. It is shown here that transfection of N-myc in a neuroblastoma cell line causes suppression of one isoform of protein kinase C, named delta, and induction of an unusual type of protein kinase C, named zeta. N-myc-transfected neuroblastoma cells were found to be blocked in the activation of both c-fos mRNA and the NF-kappa B transcription factor by phorbol ester. Introduction of a protein kinase C expression vector in N-myc transfected neuroblastoma cells restored inducibility of both c-fos and NF-kappa B by phorbol ester. These observations indicate that changes in protein kinase C gene expression significantly alter the response of N-myc-amplified neuroblastomas to a variety of external signals.
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PMID:N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma. 190 12

Previous reports have shown that thrombin and activators of protein kinase C (PKC) inhibit neurite outgrowth (NOG) in neuroblastoma cells cultured in serum-free medium. Therefore, we tested the hypothesis that PKC activation mediates the effect of thrombin on NOG in murine neuroblastoma NB-2a cells. After 2 h in serum-free medium, 70% of the cells displayed neurites; addition of 300 ng/ml thrombin reduced NOG to 24% within 1 h. This inhibition was reduced after NB-2a cells were pretreated for 24 h with 200 nM phorbol dibutyrate down-regulate PKC. Thrombin and phorbol 12-myristate 13-acetate inhibited NOG in an additive way and the protein kinase inhibitors H-7, H-8, and HA1004 reversed the effect of thrombin on NOG with a rank order of activity consistent with PKC inhibition. Furthermore, PKC was translocated from the cytosol to a membrane-bound form 5 to 10 min after addition of thrombin. These findings indicate that thrombin inhibits NOG through a PKC-dependent pathway. Thrombin stimulates the synthesis of the phospholipid platelet-activating factor (PAF) in some cells. However, NOG was markedly stimulated when PAF or its analogue carbamyl-PAF were added to NB-2a cells in medium with serum. Furthermore, the PAF receptor antagonist SRI 63072 inhibited NOG in NB-2a cells in serum-free medium. These cells accumulated PAF with kinetics similar to that of NOG inducPAF was synthesized by the de novo pathway, as shown by the incorporation of [3H]choline. These findings suggest that PAF is a mediator of NOG in NB-2a cells. Thrombin neither stimulates nor inhibits PAF synthesis in these cells.
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PMID:Modulation of neurite outgrowth in neuroblastoma cells by protein kinase C and platelet-activating factor. 191 84

The M current, IM, a voltage-dependent non-inactivating K current, was recorded in NG108-15 neuroblastoma x glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied inhibition of the M current by bradykinin, phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC), and methylxanthines. Focal application of 0.1-5 microM bradykinin inhibited IM by about 60%; 5 nM bradykinin inhibited by about 40%. Bath application of 0.1 microM and 1 microM PDBu diminished IM to about half of the control value. Staurosporine, a PKC inhibitor, applied for 35-43 min in a concentration of 0.3 microM significantly reduced the effect of 1 microM PDBu. M current blockage by PDBu could be partly reversed by bath application of H-7 (51-64 microM), another PKC inhibitor. These observations suggest that the PDBu effect is really due to activation of PKC. The findings are compatible with the view [Brown DA, Higashida H (1988) J Physiol (Lond) 397:185-207] that the bradykinin effect on IM is mediated by PKC. However, three further observations suggest that this is only true for part of the bradykinin effect. When the suppression of IM by 1 microM PDBu was fully developed, 0.1 microM bradykinin produced a further inhibition of IM. Down-regulation of PKC by long-term treatment with PDBu reduced the effect of 0.1 microM bradykinin significantly but did not abolish it. Staurosporine (0.3 microM, applied for 31-46 min) failed to reduce the effect of 5 nM bradykinin significantly. The M current could be reversibly blocked by methylxanthines (caffeine, isobutyl-methylxanthine, theophylline) in the millimolar range, probably because of a direct action on the M channels.
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PMID:Inhibition of the M current in NG 108-15 neuroblastoma x glioma hybrid cells. 194 51

Clones possessing inserts of brain myosin II have been obtained by screening a rat brain cDNA expression library with a polyclonal antibody, raised against myosin II from the mouse neuroblastoma cell line, Neuro-2A. A partial sequence comprising the 3' coding and non-coding regions of the myosin message has been determined which is markedly different from other myosin sequences. The derived amino-acid sequence comprises the C-terminal 90 amino acids: VSS(PO4)LKNKLRRGDLPFVVTRRLVRKGTLELS(PO4)DDDDESKASLINETQPPQCLDQQ LDQQ LDQLFNWPVNAGCVCGWGVEQTQGEEAVHKCRT(CO2H). This sequence encompasses regions homologous to both the casein kinase II and protein kinase C heavy-chain phosphorylation sites. The non-helical "tail-piece" is considerably longer (an additional 39 amino acid residues) than found in other myosins. Northern blot analysis demonstrates this myosin II message to be unique to cerebral cortex, with no expression in all other non-cortical brain regions and peripheral tissues tested. Our results suggest functional diversity for myosin II isozymes within the brain.
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PMID:A unique cellular myosin II exhibiting differential expression in the cerebral cortex. 923 40

We have investigated the coupling of muscarinic acetylcholine receptors (mAChR) to phospholipid hydrolysis in a human neuroblastoma cell line, LA-N-2, by measuring the formation of 3H-inositol phosphates (3H-IP) and of [3H]phosphatidylethanol ([3H]PEt) in cells prelabeled with [3H]inositol and [3H]oleic acid. The muscarinic agonist carbachol (CCh) stimulated the phospholipase C (PLC)-mediated formation of 3H-IP in a time- and dose-dependent manner (EC50 = 40-55 microM). In addition, in the presence of ethanol (170-300 mM), CCh elevated levels of [3H]PEt [which is regarded as a specific indicator of phospholipase D (PLD) activity] by three- to sixfold. The effect of CCh on PEt formation also was dose dependent (EC50 = 50 microM). Both effects of CCh were antagonized by atropine, indicating that they were mediated by mAChR. Incubation of LA-N-2 cells with the phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1 microM; 10 min) increased [3H]PEt levels by up to 10-fold. This effect was inhibited by the protein kinase C (PKC) inhibitor staurosporine (1 microM) or by pretreatment for 24 h with 0.1 microM PMA, by 74% and 65%, respectively. In contrast, the effect of CCh on PEt accumulation was attenuated by only 28% in the presence of staurosporine (1 microM). In summary, these results suggest that, in LA-N-2 neuroblastoma cells, mAChR are coupled both to phosphoinositide-specific PLC and to PLD. PKC is capable of stimulating PLD activity in these cells; however, it is not required for stimulation of the enzyme by mAChR activation.
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PMID:Stimulation of phospholipase D activity in human neuroblastoma (LA-N-2) cells by activation of muscarinic acetylcholine receptors or by phorbol esters: relationship to phosphoinositide turnover. 200 44

The effect of alpha-tocopherol (vitamin E) on the proliferation of vascular smooth muscle cells (A7r5), human osteosarcoma cells (Saos-2), fibroblasts (Balb/3T3), and neuroblastoma cells (NB2A) has been studied. The proliferation of vascular smooth muscle cells was inhibited by physiologically relevant concentrations of alpha-tocopherol, neuroblastoma cells were only sensitive to higher alpha-tocopherol concentrations, and proliferation of the other cell lines was not inhibited. The inhibition of smooth muscle cell proliferation was specific for alpha-tocopherol. Trolox, phytol, and alpha-tocopherol esters had no effect. Proliferation of smooth muscle cells stimulated by platelet-derived growth factor or endothelin was completely sensitive to alpha-tocopherol. If smooth muscle cells were stimulated by fetal calf serum, proliferation was 50% inhibited by alpha-tocopherol. No effect of alpha-tocopherol was observed when proliferation of smooth muscle cells was stimulated by bombesin and lysophosphatidic acid. The possibility of an involvement of protein kinase C in the cell response to alpha-tocopherol was suggested by experiments with the isolated enzyme and supported by the 2- to 3-fold stimulation of phorbol ester binding induced by alpha-tocopherol in sensitive cells. Moreover, alpha-tocopherol also caused inhibition of protein kinase C translocation induced by phorbol esters and inhibition of the phosphorylation of its 80-kDa protein substrate in smooth muscle cells. A model is discussed by which alpha-tocopherol inhibits cell proliferation by interacting with the cytosolic protein kinase C, thus preventing its membrane translocation and activation.
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PMID:Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C. 200 76


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