Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SH-SY5Y human neuroblastoma cells can be induced to differentiate to mature ganglion cells when treated with the phorbol ester tetradecanoylphorbol acetate (TPA). Bryostatins are a new class of protein kinase C activators that are structurally unrelated to phorbol esters. This paper describes the effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y cells. Both bryostatins induced a rapid translocation of protein kinase C from the cytosol to the membrane fraction. Within 24 h, the bryostatins had caused a nearly complete down-regulation of the enzyme. Bryostatin 1 competed for [3H]phorbol-12,13-dibutyrate binding in intact cells with potency equal to that of TPA, in contrast to bryostatin 2, which exhibited a Ki value 1 order of magnitude higher than those of the two other agents. Bryostatins induced morphological changes similar to those induced by TPA. These changes were, however, only transient, occurring during the first 6 h of incubation in the presence of these compounds. By 72 h, the cells had acquired a morphology typical of untreated cells and, although a wide range of bryostatin concentrations were used, morphological changes characteristic of differentiated SH-SY5Y cells were not detected at 72 h. Bryostatin 1 at 5 nM and bryostatin 2 at 100 nM inhibited DNA synthesis, as measured by incorporation of [3H]thymidine by SH-SY5Y cells, although to a significantly lesser degree than TPA. In spite of the fact that bryostatins failed to induce morphological differentiation in SH-SY5Y cells, these compounds down-regulated c-myc mRNA expression. Bryostatins were significantly weaker in stimulating noradrenaline synthesis, compared with TPA, and high concentrations of these agents blocked the effect of the phorbol ester when they were included together with TPA. When SH-SY5Y cells were incubated in the presence of high concentrations of bryostatins, a decreased sensitivity of cells to muscarinic agonist-induced increases in cytosolic free Ca2+ was observed. The results suggest that down-regulation of protein kinase C activity and c-myc mRNA expression do not necessarily correlate with the morphological differentiation of SH-SY5Y cells.
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PMID:Effects of bryostatins 1 and 2 on morphological and functional differentiation of SH-SY5Y human neuroblastoma cells. 233 38

The role of muscarinic receptor-mediated polyphosphoinositide hydrolysis and subsequent calcium signals in altering the subcellular localization of calmodulin (CaM) was examined in SK-N-SH human neuroblastoma cells. Upon incubation of the cells with the full agonist carbachol, a 4.5- to 5-fold increase in CaM in the cytosol was observed, from 126 ng of CaM to 629 ng of CaM. There was an accompanying 68% decrease in membrane-bound CaM. The increase in the cytosol was maximal by 15 min, as was a corresponding decrease in membrane-associated CaM. The redistribution of CaM was maintained for at least 2 hr, before returning toward control levels by 4 hr. The EC50 values for carbachol in eliciting the translocation were 3.7 microM for the increase in cytosol and 1.3 microM for the decrease in membranes. The maximal changes in CaM concentration in both membranes and cytosol occurred with 10 microM carbachol. Incubation of the SK-N-SH cells with the partial muscarinic agonists bethanechol and arecoline resulted in 27 and 26% decreases in membrane-associated CaM, respectively, and 28 and 35% increases in cytosolic CaM, respectively. Thus, the partial agonists were less efficacious than carbachol in eliciting changes in CaM localization. Atropine completely blocked the carbachol-stimulated translocation, whereas the nicotinic agonist 1,1-dimethyl 4-phenylpiperazinium had no effect on the localization of CaM. Activation of receptors coupled to adenylate cyclase did not affect distribution of CaM. CaM content in membranes and cytosol of cells incubated with prostaglandin E1 or the alpha 2-adrenergic agonist UK 14,304 was not different from control values. The ionophore ionomycin (10 microM) and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) (50 nM) were both able to elicit changes in CaM distribution. Ionomycin caused a 64% increase in CaM in the cytosol, with no significant change in membrane CaM. TPA elicited a decrease in membrane-associated CaM, with a corresponding increase in CaM in the cytosol. When TPA and ionomycin were incubated together, the translocation was equal in magnitude to that observed with carbachol alone. The protein kinase C inhibitor H-7 blocked the TPA-stimulated response and partially blocked the carbachol-stimulated response. The CaM-binding protein neuromodulin, which demonstrates a decreased affinity for CaM in the presence of Ca2+ and when phosphorylated by protein kinase C, was present in both membranes and cytosol of SK-N-SH cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Muscarinic receptor-mediated translocation of calmodulin in SK-N-SH human neuroblastoma cells. 235 3

Human neuroblastoma cells were cultured either in the absence or presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) known to induce neuronal differentiation. This treatment led to a marked increase in the concentration of secretogranin II but to a decrease of chromogranin A. Analogous changes were observed for the respective mRNAs. Thus during differentiation of these cells the biosynthesis of two vesicle constituents of large dense core vesicles is differentially regulated as determined both at the mRNA and the protein level. Levels of both synaptin/synaptophysin large dense core vesicles is differentially regulated as determined both at the mRNA and the protein level. Levels of both synaptin/synaptophysin and SV2 were also elevated but to a smaller degree than that of secretogranin II.
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PMID:Divergent changes of chromogranin A/secretogranin II levels in differentiating human neuroblastoma cells. 236 53

The effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-didecanoate (PDD) on VIP/PHM-27 gene expression in human neuroblastoma cells in culture were investigated. Bt2cAMP and phorbol esters increased the VIP/PHM-27 mRNA level by about 9- and 4-fold, respectively. In the presence of both Bt2cAMP and phorbol esters, the VIP/PHM-27 mRNA level increased by about 36-fold. The intracellular cAMP level was essentially unaffected by phorbol esters. The VIP/PHM-27 gene dosage was unchanged by Bt2cAMP and phorbol esters. The results suggest that cAMP and phorbol esters synergistically induce the VIP/PHM-27 gene expression through independent pathways.
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PMID:Synergistic stimulation of VIP/PHM-27 gene expression by cyclic AMP and phorbol esters in human neuroblastoma cells. 241 13

Mouse neuroblastoma X embryonic Chinese hamster brain explant hybrid cell line (NCB-20) forms functional synapses when intracellular cyclic AMP levels are elevated for a prolonged period of time. NCB-20 cells were labeled with [32P]orthophosphate under conditions where 2-chloroadenosine gave maximum increases of 32P incorporation into tyrosine hydroxylase in nerve growth factor dibutyryl cyclic AMP-differentiated PC12 (pheochromocytoma) cells. When NCB-20 cells were exposed to activators [5-hydroxytryptamine (5-HT), prostaglandin E1, or forskolin], resulting in activation of cyclic AMP-dependent protein kinase, increased 32P incorporation into two major proteins [130 kilodaltons (kDa) and 90 kDa] occurred. 5-HT (in the presence of phosphodiesterase inhibitor, isobutylmethylxanthine) gave a three- to fourfold increase, and forskolin a four- to sevenfold increase in 32P incorporation into the 90-kDa protein. [D-Ala2,D-Leu5]-enkephalin, which decreased cyclic AMP levels and reversed the 2-chloroadenosine-stimulated phosphorylation of tyrosine hydroxylase in differentiated PC12 cells, also reversed the stimulation of phosphorylation of the 90-kDa protein in NCB-20 cells. Pretreatment of NCB-20 cells with a calcium ionophore, A23187, gave increased phosphorylation of the 90- and 130-kDa proteins, but phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (tumor promoting agent), cell depolarization with high K+, or pretreatment with dibutyryl cyclic GMP had no effect on phosphorylation of these proteins. In contrast, phosphorylation of an 80-kDa protein was decreased by forskolin, but increased following activation of the calcium/phospholipid-dependent kinase with tumor promoting agent. Neither the 90-kDa nor the 80-kDa protein showed any immunological cross-reactivity with synapsin, a major synaptic protein known to be phosphorylated by cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase, but not calcium/phospholipid-dependent protein kinase. This suggests that in NCB-20 cells, several unique proteins can be phosphorylated by cyclic AMP-dependent protein kinase in response to hormonal elevation of cyclic AMP levels. In contrast, an 80-kDa protein is the primary substrate for calcium/phospholipid-dependent protein kinase, and its phosphorylation is inhibited by agents that elevate cyclic AMP levels and thereby activate cyclic AMP-dependent protein kinase.
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PMID:Neuromodulator-mediated phosphorylation of specific proteins in a neurotumor hybrid cell line (NCB-20). 245 Jan 74

Single channel recordings were obtained from inside-out patches of cultured human neuroblastoma cells (cell line SH-SY5Y) treated with a phorbol ester, 12-o-tetradecanoylphorbol-13-acetate (TPA) to induce differentiation. An outward current reversing near the calculated reversal potential for potassium was detected. This channel is transiently active at membrane potentials between -40 and -70 mV but with preceding hyperpolarizing pulses also at more positive potentials, up to +75 mV. The current seems to consist of two components; a slowly activating component at potentials negative to -40 mV and a fast component, more sensitive to 4-aminopyridine, seen at more positive potentials.
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PMID:Single transient potassium channels in human neuroblastoma cells induced to differentiate in vitro. 245 91

The sensitivity and selectivity of high-resolution gas chromatography/mass spectrometry in the negative ion chemical ionization mode with methane as reagent gas was evaluated for the characterization of polar substituted polycyclic aromatic compounds (PAC). The fragmentation patterns were affected by the nature of the substituent for polar substituted nitro-PAC that showed detection limits of 50 pg at full-scan acquisition. This technique has been applied to the characterization of polar high-performance liquid chromatographic fractions of diesel exhaust particulate (NBS Standard Reference Material 1650) and enabled the identification of 20 PAC of different chemical classes. Among them, hydroxynitro-, dinitro- and nitrosubstituted secondary amines were identified for the first time in diesel exhaust particulate. In addition, 'filament-on' thermospray (TSP) liquid chromatography/mass spectrometry (LC/MS) with positive and negative ions have been used for the characterization of similar polar compounds such as 2-nitroquinoline, 1,8-naphthalic anhydride, naphthalene sulphonic acid and 1,2-hydroxynitronaphthalene. LC analyses were performed on a reversed-phase system using either acetonitrile-water or methanol-water with 0.1 M ammonium acetate and 1% acetic acid as eluent. With negative ion TSP LC/MS a four- to fivefold loss in sensitivity was observed for naphthalene sulphonic acid compared with nitrohydroxy-PAC, that showed a minimum detectable amount of 50 ng in the reconstructed ion chromatogram.
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PMID:Characterization of polar substituted polycyclic aromatic compounds using high-resolution gas chromatography/mass spectrometry negative ion chemical ionization and positive and negative ion thermospray liquid chromatography/mass spectrometry. 246 74

Human SH-SY5Y neuroblastoma cells treated with retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or nerve growth factor differentiated morphologically to neuronlike cells with increased amounts of neurofilament protein and mRNA. All three effectors induced an increase in the amount of relative molecular weight (Mr) 70,000 tissue-type plasminogen activator (t-PA) and its mRNA, as determined by immunocapture, enzyme activity, and Northern blotting analyses. About 90% of the t-PA activity was secreted to the culture medium. In contrast, of the three effectors studied, only TPA induced transcription of the proto-oncogene c-fos, studied as a control gene responsive to various stimuli, and induced a rapid increase in urokinase-type PA (u-PA). Most of the u-PA activity induced by TPA remained cell-associated. Because induction of differentiation correlated closely with induction of t-PA, and not u-PA, the authors propose that t-PA may have a functional role in the morphological differentiation of neuronal cells.
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PMID:Induction of morphological differentiation of human neuroblastoma cells is accompanied by induction of tissue-type plasminogen activator. 250 35

We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human-recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.
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PMID:Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. 250 93

The fibrinolytic enzyme profile of SMS-KAN human neuroblastoma cells was found to vary dramatically during the differentiation process. Five maturational agents--retinoic acid, dibutyryl cAMP, 5-bromodeoxyuridine, sodium butyrate and phorbol myristate acetate were tested for their effects on cellular morphology, DNA synthesis, plasminogen activator (PA) and PA inhibitor (PAI) activity. SMS-KAN cells secrete urokinase (UK) and tissue PA (tPA) as well as a possibly unique PAI. Treatment of cells with 1 microM RA resulted in an inhibition of proliferation, extension of neurite-like processes indicative of differentiation, as well as a switch from secretion of UK to tPA and a reduction in PAI secretion. Other agents which caused neural process formation and decreased cell proliferation also induced alterations in PA/PAI while agents which had no detectable effect on cell growth induced little change in the fibrinolytic enzyme profile.
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PMID:Alterations in plasminogen activator and inhibitor activity during the differentiation of a human neuroblastoma cell line, SMS-KAN. 253 81


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