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)

The BE(2)-C human neuroblastoma has been shown to express corticotropin-releasing factor (CRF) messenger RNA. In this study, BE(2)-C cells were treated 5 days with 5 microM retinoic acid. Cell extracts were also applied onto a C18 Vydac column and fractions were assayed for CRF-like immunoreactivity (CRF-LI) which coincided in time of elution with oxidized or non-oxidized CRF synthetic CRF standard. With forskolin treatment, secretion media and cell extract CRF-LI increased in a concentration-dependent fashion. Thus, this cell line synthesizes and secretes CRF and is a good model for studying CRF regulation.
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PMID:Corticotropin-releasing factor is secreted in the BE(2)-C neuroblastoma cell and is responsive to forskolin. 819 96

This paper describes the preparation of monosialoganglioside GM1 with sialidase-producing marine bacteria as a microbial biocatalyst. A new sialidase-producing bacterium, identified tentatively as Pseudomonas sp. strain YF-2, was isolated from seawater by enrichment culture with ganglioside as the sole source of carbon. When YF-2 was cultured in a synthetic medium containing crude bovine brain gangliosides at 25 degrees C for 3 days, 80 to 90% of the gangliosides were converted to GM1. GM1 was then purified from the supernatant of YF-2 culture by C18 reverse-phased chromatography, followed by DEAE-Sephadex A25 anion-exchange chromatography. In a typical experiment, 178 mg of highly purified GM1 was obtained from 500 mg of the crude ganglioside fraction. The GM1 induced neurite outgrowth of neuroblastoma Neuro2a cells at a concentration of 33 to 100 microM in the presence of fetal calf serum. Sialidase was purified 33-fold with 13.3% recovery from the culture supernatant of YF-2. The purified enzyme hydrolyzed polysialogangliosides to produce GM1 but did not act on GM1. It was therefore concluded that polysialogangliosides in the culture of strain YF-2 were converted to GM1 by this sialidase.
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PMID:Preparation of GM1 ganglioside with sialidase-producing marine bacteria as a microbial biocatalyst. 914 18

Much discussion has centered on the biochemical mechanism by which ceramide is produced and functions as a signalling molecule in cells. To identify proteins involved in ceramide signalling, we synthesized a radioactively labelled ceramide analogue equipped with a photosensitive group: N-(p-trifluoromethyl-diazirinyl)phenyl-ethyl-2-[35S]-2-thioacetyl-D-erythro-C18-sphingosine ([35S]-TDS-ceramide). This compound was then employed in photo-affinity labelling experiments in primary cultured cerebellar neurons. Due to the hydrophobic nature of the compound, most of the cell-associated radioactivity was recovered in the lipid fraction while only about 0.1% of radioactivity was photocoupled to proteins. In order to improve protein labelling the cytosolic fraction of rapidly growing human neuroblastoma cells (SH-SY5Y) was isolated and subjected to ceramide affinity chromatography prior to photo-affinity labelling. Following electrophoresis proteins photocoupled to ceramide were identified by MALDI mass spectrometry in combination with tryptic digestion and turned out to be either cytoskeletal or stress proteins that are highly abundant in cytosol and contain at least one hydrophobic domain.
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PMID:Identification of ceramide binding proteins in neuronal cells: a critical point of view. 1237 6

A variety of anti-cancer drugs elevate endogenous ceramide, thereby inducing apoptosis in tumor cells. Recently, we have introduced novel ceramide analogs of the beta-hydroxy alkyl amide type, which trigger pro-apoptotic signaling pathways without prior elevation of endogenous ceramide. They induce apoptosis specifically in rapidly dividing neuroblastoma cells, but not in resting or differentiated cells. We characterize new ceramide mimics that have been derived from N-acylation of serinol (S), diethanolamine (B), propanolamine (P), and tris(hydroxy-methyl)methylamine (T) with myristic (14), palmitic (16), or oleic (18) acid. The water solubility of these compounds exceeds that of ceramide by more than 100-fold (up to 5 mM). Apoptosis of human neuroblastoma, glioma, medulloblastoma, and adenocarcinoma cells is induced by N-(2-hydroxy-1-(hydroxymethyl)ethyl)-palmitoylamide, C16-serinol (S16), N-(2-hydroxy-1-(hydroxymethyl)ethyl)-oleoylamide, C18-serinol (S18), N-bis(2-hydroxyethyl)-myristoyl-amide (B16), and N-tris(hydroxymethyl)methyl-oleoylamide (T18) within 60 min of incubation, and is completed even after removal of the compound from the medium. This is most likely due to a rapid uptake of the analogs followed by their slow release from the cells. Alteration of the acyl chain length to less than 14 methylene units, removal of the amino group, or reducing the number of hydroxyalkyl residues to less than two significantly lowers or eliminates the pro-apoptotic potential of these compounds. The target specificity of novel ceramide analogs for tumor cells, their water solubility, and fast pro-apoptotic mechanism indicates a high therapeutic potential for cancer treatment.
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PMID:Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. 1243 Jan 79

Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology. These similarities in the literature suggested the exploration of lipids in sera of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which is typically used for screening ciguateric ocean fish. Sera from patients with other diseases, including hepatitis B, cancer, and diabetes, were included to assess the degree of specificity involved. Sera were treated with acetone in a ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted acetone fraction of the 37 normal showed +/- activity to +activity with 16 no titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40 titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer, 50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or =1:40 titer. Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These data are summarized in Fig. 1. As shown in Table 1, a significant increase (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal group. A preliminary chemical study in C18 octadecylsilyl columns showed all fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol, and 100% methanol) to contain lipids reactive to MAb-CTX with different intensities. Prostaglandins were shown in 100% methanol fraction. Competitive MIA with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope suggested similarities in structure with ciguatoxin. This was compatible with the neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1, chloroform : methanol solvents.
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PMID:Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX. 1278 62

GM1a [Gal beta1-3GalNAc beta1-4(NeuAc alpha2-3)Gal beta1-4Glc beta1-1Cer] is known to support and protect neuronal functions. However, we report that alpha-linolenic acid-containing GM1a (C18:3-GM1a), which was prepared using the reverse hydrolysis reaction of sphingolipid ceramide N-deacylase, induced apoptosis in neuronal cells. Intranucleosomal DNA fragmentation, chromatin condensation, and caspase activation, all typical features of apoptosis, were observed when mouse neuroblastoma Neuro2a cells were cultured with C18:3-GM1a but not GM1a containing stearic acid (C18:0) or oleic acid (C18:1). The phenotype of Neuro2a cells induced by C18:3-GM1a was similar to that evoked by lyso-GM1a. However, lyso-GM1a caused a complete disruption of lipid microdomains of Neuro2a cells and hemolysis of sheep erythrocytes, whereas C18:3-GM1a did neither. C18:3-GM1a, but not lyso-GM1a, was found to be abundant in lipid microdomains after the removal of loosely bound GM1a by BSA. The activation of stress-activated protein kinase/c-Jun N-terminal kinase in Neuro2a cells was observed with lyso-GM1a but not C18:3-GM1a. These results indicate that the mechanism of apoptosis induced by C18:3-GM1a is distinct from that caused by lyso-GM1a. This study also clearly shows that fatty acid composition of gangliosides significantly affected their pharmacological activities when added to the cell cultures and suggests why naturally occurring gangliosides do not possess polyunsaturated fatty acids as a major constituent.
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PMID:C18:3-GM1a induces apoptosis in Neuro2a cells: enzymatic remodeling of fatty acyl chains of glycosphingolipids. 1577 22

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

Efficient extraction and accurate analysis of lipophilic brevetoxins (PbTxs), produced by the harmful algal bloom (HAB) species Karenia brevis, are essential when assessing the toxicological potential of this dinoflagellate. One of the most commonly used brevetoxin extraction methodologies employs C18 solid-phase extraction (SPE). In this study, C18 SPEC discs were tested for extraction of spiked PbTx-3 in seawater and naturally produced brevetoxins from K. brevis. Quantification of brevetoxin in the extracts was determined using four independent methods: receptor binding assay (RBA), radioimmunoassay (RIA), neuroblastoma (N2A) cytotoxicity assay, and liquid chromatography/mass spectrometry (LC/MS). In addition to quantification of the brevetoxin concentration, LC/MS analysis provided identification of individual congeners and each of their hydrolyzed products. SPEC disc extractions prepared from sonicated cultures of non-brevetoxin-producing Karenia mikimotoi cultures spiked with PbTx-3 yielded extraction efficiencies of 108, 99, and 125% as determined by the RBA, RIA, and N2A cytotoxicity assay, respectively. In SPEC disc extracts of brevetoxin-producing K. brevis (isolate SP3) cultures, LC/MS analysis yielded the highest total concentrations, possibly due to the concurrent detection of hydrolytic brevetoxin congeners that accounted for up to 20% of the congener profile. Relative to the brevetoxin concentration as determined by LC/MS, the RBA, RIA, and N2A cytotoxicity assay detected 73, 83, and 51% of the total brevetoxin concentration. Stability experiments demonstrated that brevetoxins remain stable on the SPEC discs for at least 30 days, making this extraction method suitable for shipboard collections.
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PMID:Extraction and analysis of lipophilic brevetoxins from the red tide dinoflagellate Karenia brevis. 1766 54

A simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method using an atmospheric pressure chemical ionization source (APCI) for the quantification of fenretinide (4-HPR) in mouse plasma was developed and validated. After a simple protein precipitation of plasma sample by acetonitrile, 4-HPR was analyzed by LC-APCI-MS/MS. High-performance liquid chromatography (HPLC) separation was conducted on a Hypurity C18 column (50mmx2.1mm, 5microm) with a flow rate 0.60mL/min using a gradient mobile phase comprised of 0.05% formic acid in water (A) and methanol (B), and a run time of 4.5min. The elimination of a tedious sample preparation process and a shorter run time substantially reduced total analysis time. The method was linear over the range 0.5-100ng/mL, with r>0.998. The intra- and inter-assay precisions were 1.4-9.2% and 5.1-8.2%, respectively, and the intra- and inter-assay accuracies were 93.9-98.6% and 92.7-95.3%, respectively. The absolute recoveries were 90.3% (1.5ng/mL), 97.0% (7.5ng/mL) and 92.1% (75.0ng/mL) for 4-HPR, and 99.1% for the internal standard (150ng/mL). The analytical method had excellent sensitivity using a small sample volume (30microL) with the lower limit of quantification (LLOQ) 0.5ng/mL. This method is robust and has been successfully employed in a pharmacokinetic study of 4-HPR in a mouse xenograft model of neuroblastoma.
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PMID:A rapid, sensitive and selective liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for determination of fenretinide (4-HPR) in plasma. 1803 19

Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/omega-3) and arachidonic acid (C18:4/omega-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid- and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.
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PMID:Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease. 1892 92


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