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)

In order to study the endocytosis of membrane lipids during the development of neuronal polarity, we examined the internalization of a short acyl chain fluorescent derivative of ganglioside GM1, N-(6-(4-nitrobenz-2-oxa-1,3-diazole-7-yl)-aminohexanoyl)-GM1 (C6-NBD-GM1), in hippocampal neurons cultured at low density. C6-NBD-GM1 was internalized by temperature- and energy-dependent mechanisms, and after short times of incubation, accumulated in endosomes in the axon, cell body and dendrites of neurons maintained for up to 4-5 days in culture. C6-NBD-GM1 was subsequently transported in a retrograde direction to a pool of recycling endosomes in the cell body, with little transport to lysosomes, as indicated by the lack of degradation of C6-NBD-GM1 even after long times, and the re-appearance of intact C6-NBD-GM1 at the cell surface after recycling; similarly, little degradation of C6-NBD-GM1 was detected in N18TG-2 neuroblastoma cells. In hippocampal neurons maintained for longer than 6 days in culture, there was little internalization of C6-NBD-GM1 along the length of axons, but the amount of endocytosis from dendrites was similar to that observed in younger neurons. These results demonstrate that gangliosides turnover rapidly in dendritic membranes at all stages of neuronal development, whereas ganglioside turnover in axons is much less rapid, at least in mature, polarized neurons.
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PMID:The internalization of a short acyl chain analogue of ganglioside GM1 in polarized neurons. 885 7

Various glycolipid-binding toxins are internalized from the cell surface to the Golgi apparatus. Prominent among these is cholera toxin (CT), which consists of a pentameric B subunit that binds to ganglioside GM1 and an A subunit that mediates toxicity. We now demonstrate that rhodamine (Rh)-CT can be further internalized from the Golgi apparatus to the endoplasmic reticulum (ER) in cultured hippocampal neurons and in neuroblastoma N18TG-2 cells and that the A subunit is essential for retrograde transport to the ER. In addition, the rate of internalization of Rh-CT to the Golgi apparatus and ER decreases dramatically as hippocampal neurons mature. The Golgi apparatus was labeled in almost all 1-day-old neurons after < 1 h of incubation with Rh-CT but was labeled in < 10% of 14-day-old neurons after 1 h. During the first 14 days in culture, there was a 15-fold increase in the number of 125I-CT-binding sites per cell, indicating that the decrease in the rate of internalization of Rh-CT is not due to reduced levels of cell surface GM1 in older neurons. These results imply that the rate of retrograde transport of CT from the plasma membrane to the Golgi apparatus and ER is regulated during neuronal development and differentiation.
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PMID:Rate of retrograde transport of cholera toxin from the plasma membrane to the Golgi apparatus and endoplasmic reticulum decreases during neuronal development. 886 23

Gangliosides have attracted particular attention in the field of brain research, since they were found not only to be abundant in neural tissue but also to have intricate structures in synaptic membranes. A murine neuroblastoma cell line, Neuro2a, expresses negligible amounts of GM3 and b-series gangliosides, but significant amounts of a-series gangliosides (GM1 and GD1a). With the transfection of cDNA encoding GD3 synthase, the de novo synthesis and expression of GD3 and b-series gangliosides occurred, and, furthermore, it induced the growth of axon-like neurites and cholinergic differentiation of Neuro2a cells. On the other hand, with the transfection of an alpha 1,2-fucosyltransferase, the axon-like neurite outgrowth was suppressed and dendrite-like neurites were outgrowth. These observations directly demonstrate the primary importance of the gene expression of a glycosyltransferase, and of the subsequent biosynthesis of gangliosides and their expression on the cell surface for neural cell development and differentiation.
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PMID:New evidence for the occurrence of a glycolipid-mediated signal transduction system. 890 74

Results of transgenetic studies argue that the scrapie isoform of the prion protein (PrPSc) interacts with the substrate cellular PrP (PrPC) during conversion into nascent PrPSc. While PrPSc appears to accumulate primarily in lysosomes, caveolae-like domains (CLDs) have been suggested to be the site where PrPC is converted into PrPSc. We report herein that CLDs isolated from scrapie-infected neuroblastoma (ScN2a) cells contain PrPC and PrPSc. After lysis of ScN2a cells in ice-cold Triton X-100, both PrP isoforms and an N-terminally truncated form of PrPC (PrPC-II) were found concentrated in detergent-insoluble complexes resembling CLDs that were isolated by flotation in sucrose gradients. Similar results were obtained when CLDs were purified from plasma membranes by sonication and gradient centrifugation; with this procedure no detergents are used, which minimizes artifacts that might arise from redistribution of proteins among subcellular fractions. The caveolar markers ganglioside GM1 and H-ras were found concentrated in the CLD fractions. When plasma membrane proteins were labeled with the impermeant reagent sulfo-N-hydroxysuccinimide-biotin, both PrPC and PrPSc were found biotinylated in CLD fractions. Similar results on the colocalization of PrPC and PrPSc were obtained when CLDs were isolated from Syrian hamster brains. Our findings demonstrate that both PrPC and PrPSc are present in CLDs and, thus, support the hypothesis that the PrPSc formation occurs within this subcellular compartment.
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PMID:Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. 896 61

Addition of gangliosides to neuroblastoma cells maintained in vitro has been shown to enhance neuritogenesis. Although the mechanism by which they exert this effect is unknown, it has been postulated that they may act by adhering to cell surface proteins. In this article, we describe the isolation and identification of an S20Y murine neuroblastoma cell protein recognized by a monoclonal antibody that was prepared against putative GM1-binding proteins and shown to inhibit GM1-enhanced neuritogenesis. The protein identified was nonmuscle myosin heavy chain B, which appears to function in neurite formation but may not adhere to gangliosides.
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PMID:Nonmuscle myosin heavy chain B is recognized by a monoclonal antibody that inhibits GM1-enhanced neuritogenesis. 900 45

We developed an animal model to evaluate the 125-I-metaiodobenzylguanidine (125-I-mIBG) biodistribution in tumor bearing mice. Six weeks old nude-atimic mice were subcutaneously injected with 30 x 10(6) cells of the human neuroblastoma (NB) cell line SH-SY5Y. TE-671, a rhabdomyosarcoma cell line, was used as a control tumor without a specific mIBG uptake mechanism. In order to prevent possible tumor rejection mediated by NK activity the anti asialo GM1 antiserum was administered intraperitoneally once a week for 4 weeks. The maximum anti asialo mediated effect was obtained by administering the first dose the same day as the cell implant. In this group of animals by 9 weeks 98% of mice had a measurable tumor. We have utilized this model to evaluate the biodistribution of 125-I-mIBG given as two different formulations: standard preparation with a specific activity of 84 mCi/mg and the no carrier added (n.c.a) formulation with a specific activity of approximately 8,000 mCi/mg. Our preliminary results indicate that the biodistribution of the two different formulations in the various organs are similar. Therefore it appears that n.c.a. mIBG should not cause an increased toxicity in possible normal target organs such as heart or adrenals. Additional experiments will be performed in this model to ascertain if there is a potential advantage of the clinical use of n.c.a. mIBG over the standard preparation.
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PMID:A human neuroblastoma xenograft model for 125-I-metaiodobenzylguanidine biodistribution studies. 904 44

In this study, involvement of gangliosides in neurite outgrowth and receptor expression of the neuroblastoma X glioma hybrid NG108-15 cloned cells was investigated. Monosialoganglioside GM1 (100 microM) and disialoganglioside GD1a (100 microM) were applied to the culture medium at different concentrations of fetal bovine serum, 1-10%, with or without addition of dibutyryl adenosine 3',5'-cyclic monophosphate (500 microM). In some experiments, 5 mg/ml of cholera toxin B was added to the media to block endogenous GM1. The results indicated that GM1 had an influence on cell proliferation and neuritogenesis but did not induce muscarinic receptor expression of NG108-15 cells.
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PMID:Neuritogenesis, not receptor expression, of NG108-15 cells can be modulated by monosialoganglioside GM1. 905 5

Exogenously added gangliosides are known to promote neurite outgrowth in a variety of cell types, including some neuroblastoma cell lines. To study neuritogenesis in SH-SY5Y human neuroblastoma we serum starved the cells for 24 hr and exposed them to gangliosides (GM1, GM3, or GT1b), platelet-derived growth factor (PDGF), insulin, nerve growth factor (NGF), insulin-like growth factor I (IGF-I), or combinations of these for 3 days. We measured four parameters of neurite outgrowth using image analysis. PDGF induced neurite outgrowth in SH-SY5Y and GM1 inhibited this. Both phenomena were dose-dependent with neurites/cell and neurite length being below controls with 100 microM GM1, and percent of neurite-bearing cells being below controls with 25, 50, and 100 microM GM1. Similar but more inhibitory results were obtained with GM3 and GT1b. Insulin and IGF-I induced a neuritogenic response that was less potent than that of PDGF and was also inhibited by gangliosides. NGF had no effect on neurite outgrowth but gangliosides were still inhibitory even in cells not treated with growth factors. From this we conclude that gangliosides inhibit spontaneous and trophic factor-induced neurite outgrowth in SH-SY5Y cells. For GM1 and GT1b, but not GM3, this probably involves inhibition of trophic factor receptor function.
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PMID:Gangliosides inhibit growth factor-stimulated neurite outgrowth in SH-SY5Y human neuroblastoma cells. 908 10

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

Selective acylation of mono-deacetyl lyso-GM1, i.e. beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-galactopyr ano syl -(1-->4)-(alpha-D-neuraminyl-(2-->3))-beta-D-galactopyranosyl- (1-->4)-beta-D-glucopyranosyl-(1-->1)-(2S,3R,4E)-2-amino-4-octa decen-1,3-diol, with N-succinimidyl-[1-14C]stearate afforded labeled mono-deacetyl GM1, i.e. beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-galactopyr ano syl- (1-->4)-(alpha-D-neuraminyl-(2-->3)-beta-D-galactopyranosyl-(1-->4)-beta -D- glucopyranosyl-(1-->1)-(2S,3R,4E)-2-[1-14C]octadecanamido-4- octadecen-1, 3-diol, in good yield. Its condensation with either N-succinimidyl-digoxigenyl-3-O-methyl carbonyl-epsilon-amino caproate or N-succinimidyl-D-biotinyl-epsilon-aminocaproate led to radioactive GM1 derivatives carrying a tag for immuno-electron microscopy at the sialic acid residue. These GM1 derivatives could be hydrolyzed to the corresponding GM3 derivatives by treatment with GM1-beta-galactosidase and beta-hexosaminidases. There was no further degradation by sialidases due to the bulky tag in the sialic acid residue. The uptake of biotin labeled GM1 by human skin fibroblasts, rat neuroblastoma cells B104 and human neuroblastoma cells SHSY5Y was 0.85, 0.58 and 1.62 nmol lipid/mg cellular protein, respectively, after an incubation for 66 h at 37 degrees C and was similar to that of untagged GM1. The uptake of digoxigenin labeled GM1 by these cell types was, however, significantly higher (3.1, 6.8, and 20.0 nmol lipid/mg cellular protein, respectively). Both the biotin and digoxigenin labeled GM1 analogs were catabolized to the corresponding GM2 and GM3 derivatives in lysosomes of cultured cells. This demonstrates that these synthetic analogues are suitable for studying, by immuno-electron microscopy, their endocytosis and distribution in intralysosomal membranes.
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PMID:Synthesis and mass spectrometric characterization of digoxigenin and biotin labeled ganglioside GM1 and their uptake by and metabolism in cultured cells. 914 88


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