Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Thymopoietins (TMPOs) are a group of ubiquitously expressed nuclear proteins. They are suggested to play an important role in nuclear envelope organization and cell cycle control, as has been shown for lamina-associated polypeptides 2 alpha and beta, which are the rat homologs of human TMPOalpha and TMPObeta, respectively. The recent isolation and characterization of seven mouse TMPO mRNA transcripts named TMPO-alpha, beta, beta', gamma, epsilon delta and zeta, suggest that more than the three previously reported transcripts, alpha, beta, and gamma forms, may exist in humans. Here we report on the demonstration of putative human TMPOdelta and epsilon by immunoblotting of human cell lines using a newly prepared polyclonal antiserum against the common N-terminal region of TMPO. Furthermore, we prepared the first truly TMPO-beta-specific, affinity-purified polyclonal antiserum, using a part of the human analog of the beta-specific domain of mouse TMPO 220-259 for immunization. We showed that human TMPObeta is highly expressed in all cancerous cells tested, while hardly any cross-reactivities with other proteins could be detected. In contrast to the high expression of human TMPObeta in the cancer-derived neuroblastoma cell lines SK-N-MC and SMS-KAN, we found very low expression of human TMPObeta in low-proliferative nerve tissue. These data led us to the assumption that expression of TMPObeta may correlate with the occurrence of cancer, and therefore may serve as a new tumor marker, or even as a new target for cancer therapy.
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PMID:On the role of thymopoietins in cell proliferation. Immunochemical evidence for new members of the human thymopoietin family. 1043 29

1. In NG108-15 neuroblastomaxglioma hybrid cells, ATP stimulates intracellular cyclic AMP formation, which is inhibited by both adenosine (P(1)) and P2 receptor antagonists. In the present study, we examined the effects of several AMP derivatives in NG108-15 cells and mouse neuroblastoma N18TG-2 cells. 2. Adenosine 2'-monophosphate (A2P), adenosine 3'-monophosphate (A3P) and adenosine 5'-phosphosulphate (A5PS) increased cyclic AMP levels with similar concentration-dependencies in NG108-15 cells. 3. Increases in cyclic AMP by AMP derivatives were inhibited by the P2 receptor antagonist PPADS, but not by suramin. Effects of AMP derivatives were also inhibited by P(1) receptor antagonists ZM241385, XAC, DPCPX and partially by alloxazine. The ecto-nucleotidase inhibitor alpha, beta-methyleneADP was without effect. 4. In contrast, AMP derivatives did not change cyclic AMP levels in N18TG-2 cells. Accumulation of cyclic AMP in N18TG-2 cells was stimulated by adenosine A(2) receptor agonists CGS21680 and NECA, but not by ATP or beta, gamma-methyleneATP, agonists for cyclic AMP production in NG108-15 cells. 5. Reverse transcription-coupled polymerase chain reaction (RT - PCR) analyses revealed that N18TG-2 cells express both A(2A) and A(2B) receptors, while NG108-15 cells express mainly A(2A) receptors. 6. AMP derivatives did not affect the P2X and P2Y receptors expressed in NG108-15 cells. 7. These results suggest that A2P, A3P and A5PS act as agonists for cyclic AMP production and that these compounds are valuable tools for determinating the mechanism of ATP-stimulated cyclic AMP response in NG108-15 cells.
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PMID:Effects of AMP derivatives on cyclic AMP levels in NG108-15 cells. 1072 74

We examined the modulation of protein kinase C (PKC) subtypes during apoptosis induced by ginsenoside Rh2 (G-Rh2) in human neuroblastoma SK-N-BE(2) and rat glioma C6Bu-1 cells. Apoptosis induced by G-Rh2 in both cell lines was confirmed, as indicated by DNA fragmentation and in situ strand breaks, and characteristic morphological changes. During apoptosis induced by G-Rh2 in SK-N-BE(2) cells, PKC subtypes alpha, beta and gamma were progressively increased with prolonged treatment, whereas PKC delta increased transiently at 3 and 6 h and PKC epsilon was gradually down-regulated after 6 h following the treatment. On the other hand, PKC subtype zeta markedly increased at 24 h when maximal apoptosis was achieved. In C6Bu-1 cells, no significant changes in PKC subtypes alpha, gamma, delta, epsilon and zeta were observed during apoptosis induced by G-Rh2. These results suggest the evidence for a possible role of PKC subtype in apoptosis induced by G-Rh2 in SK-N-BE(2) cells but not in C6Bu-1 cells, and raise the possibility that G-Rh2 may induce apoptosis via different pathways interacting with or without PKC in different cell types.
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PMID:Differential expression of protein kinase C subtypes during ginsenoside Rh2-lnduced apoptosis in SK-N-BE(2) and C6Bu-1 cells. 1105 34

Glutathione-S-transferases (GSTs) are a superfamily of enzymes that function to catalyze the nucleophilic attack of glutathione on electrophilic groups of a second substrate. GSTs are present in many organs and have been implicated in the detoxification of endogenous alpha, beta unsaturated aldehydes, including 4-hydroxynonenal (HNE). Exogenous GST protects hippocampal neurons against HNE in culture. To test the hypothesis that overexpression of GST in cells would increase resistance to exogenous or endogenous HNE induced by oxidative stress, stable transfectants of SY5Y neuroblastoma cells with GST were established. Stable GST transfectants demonstrated enzyme activities 13.7 times (Clone 1) and 30 times (Clone 2) higher than cells transfected with vector alone. GST transfectants (both Clones 1 and 2) demonstrated significantly (p <.05) increased resistance to ferrous sulfate/hydrogen peroxide (20.9% for Clone 1; 46.5% for Clone 2), amyloid beta-peptide (12.2% for Clone 1; 27.5.% for Clone 2), and peroxynitrite (24.3% for Clone 1; 43.9% for Clone 2), but not to exogenous application of HNE in culture medium. GST transfectants treated with 1,1,4-tris (acetyloxy)nonane, a nontoxic derivative of HNE that is degraded to HNE intracellularly, demonstrated a statistically significant (p <.05) increase in viability in a dose-dependent manner compared with SY5Y cells transfected with vector alone. These results suggest that overexpression of GST increases resistance to endogenous HNE induced by oxidative stress or released in the degradation of 1,1,4-tris (acetyloxy)nonane, but not to exogenous application of HNE.
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PMID:Expression of glutathione-S-transferase isozyme in the SY5Y neuroblastoma cell line increases resistance to oxidative stress. 1142 92

1. Using pharmacological analysis and fura-2 spectrofluorimetry, we examined the effects of gamma-aminobutyric acid (GABA) and related substances on intracellular Ca(2+) concentration ([Ca(2+)]i) of hybrid neurones, called MD3 cells. The cell line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal root ganglion (DRG) neurone. 2. MD3 cells exhibited DRG neurone-like properties, such as immunoreactivity to microtubule-associated protein-2 and neurofilament proteins. Bath applications of capsaicin and alpha, beta-methylene adenosine triphosphate reversibly increased [Ca(2+)]i. However, repeated applications of capsaicin were much less effective. 3. Pressure applications of GABA (100 microM), (Z)-3-[(aminoiminomethyl) thio] prop-2-enoic acid sulphate (ZAPA; 100 microM), an agonist at low affinity GABA(A)-receptors, or KCl (25 mM), transiently increased [Ca(2+)]i. 4. Bath application of bicuculline (100 nM - 100 microM), but not picrotoxinin (10 - 25 microM), antagonized GABA-induced increases in [Ca(2+)]i in a concentration-dependent manner (IC(50)=9.3 microM). 5. Ca(2+)-free perfusion reversibly abolished GABA-evoked increases in [Ca(2+)]i. Nifedipine and nimodipine eliminated GABA-evoked increases in [Ca(2+)]i. These results imply GABA response dependence on extracellular Ca(2+). 6. Baclofen (500 nM - 100 microM) activation of GABA(B)-receptors reversibly attenuated KCl-induced increases in [Ca(2+)]i in a concentration-dependent manner (EC(50)=1.8 microM). 2-hydroxy-saclofen (1 - 20 microM) antagonized the baclofen-depression of the KCl-induced increase in [Ca(2+)]i. 7. In conclusion, GABA(A)-receptor activation had effects similar to depolarization by high external K(+), initiating Ca(2+) influx through high voltage-activated channels, thereby transiently elevating [Ca(2+)]i. GABA(B)-receptor activation reduced Ca(2+) influx evoked by depolarization, possibly at Ca(2+)-channel sites in MD3 cells.
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PMID:Analysis of GABA(A)- and GABA(B)-receptor mediated effects on intracellular Ca(2+) in DRG hybrid neurones. 1152 1

Translocation of protein kinase C (PKC) alpha, beta II, delta and epsilon fused to enhanced green fluorescent protein (EGFP) was studied in living neuroblastoma cells by confocal microscopy. Exposure to carbachol elicited transient translocation of PKC alpha-EGFP and beta II-EGFP in most of the cells, PKC delta-EGFP in a few cells and induced sustained translocation of PKC epsilon-EGFP. To monitor levels of Ca(2+) and diacylglycerol and the translocation of PKC in the same cell, the Ca(2+)-sensitive C2 domain, diacylglycerol-sensitive C1 domains and full-length PKC were fused to red, cyan and yellow fluorescent proteins respectively. PKC alpha was translocated a few seconds after the C2 domain, which represents an increase in Ca(2+). This delay was insensitive to removal of the pseudosubstrate in PKC alpha, but the isolated regulatory domain translocated simultaneously with the C2 domain. Translocation of PKC epsilon coincided with the increase in diacylglycerol. Ionomycin induced translocation of PKC alpha and the C2 domain, whereas 1,2-dioctanoylglycerol caused translocation of the C1 domains and PKC epsilon, but not PKC alpha. Experiments with individual C1 domains showed that treatment with carbachol or phorbol 12,13-dibutyrate elicited translocation of PKC alpha C1a, PKC epsilon C1a and PKC epsilon C1b, whereas PKC alpha C1b was largely insensitive to these agents. In contrast with full-length PKC alpha, the regulatory domain of PKC alpha and pseudosubstrate-devoid PKC alpha responded to the carbachol-stimulated increase in diacylglycerol.
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PMID:The catalytic domain limits the translocation of protein kinase C alpha in response to increases in Ca2+ and diacylglycerol. 1246 Jan 19

Differential activation of PKC isoforms by angiotensin II (AII) has been found in a variety of tissues in which this important octapeptide mediates its multitude of effects. To date, the PKC isoforms involved in mediating brain-specific effects are yet to be defined. In the present study, the identity of PKC isoforms coupled to AII stimulation was examined in the neuroblastoma X glioma hybrid cell line, NG108-15, by Western blot analysis. This cell line expresses both the AT1 and AT2 receptor subtypes, with the AT1 subtype predominating, and expression levels highly-upregulated when cells are in the differentiated state. Six PKC isoforms were examined in the present study, including three Ca(2+) dependent (alpha, beta, and gamma), and three Ca(2+) independent (delta, and zeta) isoforms. NG108-15 cells were found to express PKC alpha, delta, and zeta isoforms but not beta or gamma isoforms. Differential sensitivity of the PKC isoforms to AII stimulation was demonstrated, with AII causing a rapid and transient activation of the PKC alpha only in undifferentiated cells, whereas both PKC alpha and isoforms were responsive in differentiated cells. PKC activation was found to be both dose- and time-dependent. The data demonstrate the differential activation of PKC isoforms to AII stimulation in NG108-15 cells, with evidence supporting the involvement of the PKC alpha and isoforms in AII-mediated effects in the brain.
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PMID:Selective activation of protein kinase C isoforms by angiotensin II in neuroblastoma X glioma cells. 1506 66

Epolactaene (compound 1), a neuritogenic compound found in human neuroblastoma cells, was found to show anti-inflammatory activity in vivo in this study. DNA polymerases and DNA topoisomerase II (topo II) were some of the major molecular targets of compound 1. Since the agent seems to be a potential pharmaceutical medicine, we synthesized derivatives chemically and obtained seven compounds, 1 to 7 to screen clinically more efficient epolactaene derivatives. A comparison of its structural derivatives revealed that the long alkyl side chain seemed to have an important role in the inhibitory effect. Notably, C18-alkyl chain conjugated epolactaene (compound 5) was the strongest inhibitor of DNA polymerase alpha, beta, lambda (pol alpha, beta, lambda) and topo II, with IC50 values of 13, 135, 4.4 and 5 microM, respectively, and 500 microg of compound 5 caused a marked reduction in TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation (inhibitory effect, 65.0%). Compound 5 did not influence the activities of plant or prokaryotic DNA polymerases, or of other DNA metabolic enzymes such as telomerase, RNA polymerase and deoxyribonuclease I. Based on these results, the relationship among the three-dimensional structure of epolactaene derivatives and the inhibition of polymerases and topo II, and anti-inflammation is discussed.
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PMID:Structural analysis of epolactaene derivatives as DNA polymerase inhibitors and anti-inflammatory compounds. 1580 99

Peroxisome proliferator-activated receptors (PPARs) play roles in neural cells by regulating energy balance, cell proliferation and anti-oxidant responses although the molecular mechanisms underlying such roles are unclear. Chronic exposure to excess manganese (Mn) leads to neurotoxicity, although Mn-induced neurotoxic mechanisms have not been fully elucidated. We hypothesized Mn neurotoxicity differentially alters the expression of PPARs. We investigated the effects of manganese chloride treatment (0.01-4 mM) on protein expression of PPAR isoforms (alpha, beta, and gamma) in human astrocytoma (U87) and neuroblastoma (SK-N-SH) cells. The two cell types expressed the 3 PPAR isoforms differentially: their expression of the PPARs was altered by Mn-treatment. Furthermore, nuclear and cytosolic fractions derived from the 2 cell types, with and without Mn-treatment, exhibited marked differences in the protein content of PPARs. Our results constitute the first demonstration that the PPAR signaling pathway may assume pathophysiological importance in Mn neurotoxicity.
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PMID:Manganese treatment modulates the expression of peroxisome proliferator-activated receptors in astrocytoma and neuroblastoma cells. 1705 72

Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde to which humans are exposed in many situations and has been implicated in neurodegenerative diseases such as Alzheimer's disease. A galloyl dimer prorobinetinidin from Acacia mearnsii De Wild, robinetinidol-(4beta-->8)-epigallocatechin 3-O-gallate (REO), has antioxidant properties and could protect brain against acrolein-induced oxidative damage. In this study, the molecular basis of acrolein-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and the modulating effects of REO were examined. Our results indicate that REO protects SH-SY5Y cells from acrolein-induced damage by the attenuation of reactive oxygen species, the remediation of NADPH oxidase activity, the enhancement of the glutathione system, and the prevention of protein oxidation/nitration and lipid peroxidation. In order to determine the effects of REO on mitochondrial events, mitochondrial membrane potentials (Delta Psim) and caspase cascades downstream of mitochondria were assessed. REO inhibited the collapse of Delta Psi m, suggesting that REO reduces the mitochondrial dysfunction associated with acrolein treatment. REO also inhibited caspase-3 activation, which can be triggered by mitochondrial malfunctions. Furthermore, REO induced a significant reduction in the level of phospho-JNK, which is known as an apoptotic mediator in acrolein-induced neuronal cell death. Our results indicate that REO protects neurons from the deleterious effects of acrolein via the attenuation of oxidative stress, NADPH oxidase activity, GSH depletion, protein oxidation/nitration, lipid peroxidation, mitochondrial dysfunction, JNK activation, and caspase activity. These findings suggest that REO could be potentially useful as a protective agent for people exposed to acrolein.
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PMID:Robinetinidol-(4beta-->8)-epigallocatechin 3-O-gallate, a galloyl dimer prorobinetinidin from Acacia mearnsii De Wild, effectively protects human neuroblastoma SH-SY5Y cells against acrolein-induced oxidative damage. 2055 45


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