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

Cytoplasmic, tubular and particulate fractions of differentiating neuroblastoma cells were prepared and the tubulin together with tubulin-like proteins was measured in each cell fraction during different stages of cell differentiation. In undifferentiated cells, 73%, 5% and 22% of the tubulin and tubulin-like proteins were contained in the cytoplasmic, tubular and particulate fractions, respectively. After 5 days of differentiation, the overall content of tubulin and tubulin-like proteins had increased by 73%. This corresponded to increases of 45%, 145% and 100% in the cytoplasmic, microtubular and particulate fractions, respectively. The increase in membrane-bound (particulate) tubulin and tubulin-like proteins was significantly greater than the total increase of proteins in the particulate fraction. Polyacrylamide gel electrophoresis of the proteins in each subcellular fraction revealed the presence of protein bands corresponding to the alpha and beta subunits of tubulin. Whereas these bands indicated equal amounts of protein in the alpha and beta positions for the tubular and particulate cell fractions, an analysis of the cytoplasmic fraction revealed much more protein migrating to the alpha-tubulin position than to the beta-tubulin position, especially during cell differentiation. Furthermore, two overlapping but distinct protein bands were demonstrable in the position of the alpha-tubulin from the cytoplasmic fraction. These bands were designated alpha 1 and alpha 2. The particulate fraction contained only the alpha 1 and the tubular fraction only the alpha 2 protein band. The addition of 1 mM dibutyryl cyclic AMP to the neuroblastoma cells, at the time when the serum was withdrawn, enhanced the rate of differentiation and the redistribution of tubulin and tubulin-like proteins within the 3 cellular compartments. These results are discussed as they relate to the regulation, biosynthesis, turnover and compartmentation of tubulin and tubulin-like proteins in differentiating neuroblastoma cells.
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PMID:Compartments of tubulin and tubulin-like proteins in differentiating neubroblastoma cells. 48 15

Insulin-like growth factors (IGFs) are implicated in the development of the vertebrate neural circuitry, and increase neurite growth in vitro and in vivo. The construction of the cytoskeleton is necessary for growth of axons and dendrites, and the neurofilament (NF) 68 kDa and 170 kDa proteins assemble to help form major fibrillar elements of the neurite cytoskeleton. We report that physiological concentrations of insulin, IGF-I or IGF-II increased the contents of 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs, relative to total RNA, in cultured human neuroblastoma SH-SY5Y cells. In contrast, the relative contents of histone 3.3 mRNA, and poly(A)+ RNA were not increased. Ligand concentrations which increased NF mRNAs were very similar to those which increased neurite outgrowth. Although each gene was evidently independently regulated, the 68 kDa NF, 170 kDa NF, alpha-tubulin, and beta-tubulin mRNAs were nevertheless all transiently elevated over approximately the same time interval in response to insulin. These data, when considered together with studies by others with nerve growth factor, show that the 68 kDa and 170 kDa NF mRNAs are elevated in a biochemical pathway activated in common during neurite outgrowth directed by insulin, IGF-I, IGF-II, and nerve growth factor.
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PMID:Effects of insulin and insulin-like growth factors on neurofilament mRNA and tubulin mRNA content in human neuroblastoma SH-SY5Y cells. 132 Jul 19

The use of a panel of monoclonal antibodies (mAbs) directed against different determinants of microtubule-associated protein 2 (MAP2) enabled us to identify two distinct high-molecular-mass MAP2 species (270 and 250 kDa) and a substantial amount of MAP2c (70 kDa) in human neuroblastoma cells. The 250-kDa MAP2 species appears to be confined to the human neuroblastoma cells and was not observed in microtubules (MTs) from bovine and rat brain, mouse neuroblastoma, or MTs from human cerebellum. A new overlay method was developed, which demonstrates binding of tubulin to human neuroblastoma high-molecular-mass MAP2 by exposing nitrocellulose-bound MT proteins under polymerization conditions to tubulin. Bound tubulin was detected with a mAb directed against beta-tubulin. The binding of tubulin to MAP2 could be abolished by a peptide homologous to positions 426-445 of the C-terminal region of beta-tubulin. Immunological cross-reactivity with several mAbs directed against bovine brain MAP2, taxol-promoted coassembly into MTs, and immunocytochemical visualization within cells were further criteria utilized to characterize these proteins as true MAPs. Indirect immunofluorescence with anti-MAP2 and anti-beta-tubulin mAbs demonstrated that there is a change in the spatial organization of MTs during induced cell differentiation, as indicated by the appearance of MT bundles and the redistribution of MAP2.
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PMID:Characterization and intracellular distribution of microtubule-associated protein 2 in differentiating human neuroblastoma cells. 169 15

A panel of 12 antibodies was used to further characterize the immunohistochemical staining profile of olfactory neuroblastoma. The following results were obtained for the 11 neoplasms that were immunostained: neuron-specific enolase 11/11(+), S-100 protein 8/11(+), microtubule-associated protein-2 8/11(+), class III beta-tubulin isotype 9/11(+), neurofilament 200 kD 8/11(+), synaptophysin 7/11(+), glial fibrillary acidic protein 1/11(+), chromogranin A 1/11(+), vimentin 1/11(+), keratin (CAM 5.2) 4/11(+), keratin (AEI/AE3) 0/11(+), and epithelial membrane antigen 0/11(+). Expression of two intermediate filaments was found in 4 of the 11 tumors. The authors' data showing that 72% of olfactory neuroblastomas were S-100 protein positive and only one was immunoreactive for glial fibrillary acidic protein agree with other published immunohistochemical studies. With only a single exception, each of the 11 neoplasms was labeled with one or more antibodies that detect neuronal cytoskeletal proteins (class III beta-tubulin isotype, microtubule-associated protein-2, neurofilament 200 kD). These immunohistochemical results are complementary to the reported electron microscopic findings of intermediate filaments and microtubules in olfactory neuroblastomas.
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PMID:Olfactory neuroblastoma. Additional immunohistochemical characterization. 204 4

Addition of concanavalin A (Con A) to mouse neuroblastoma N18TG2 cells cultured with dibutyryl-cAMP which can stimulate neurite outgrowth, stopped the neuritic processes effectively. The extended neurites showed a gradual retraction for at least 8 hrs after addition of Con A, while addition of colchicine caused rapid retraction of the neurites. Immunocytochemistry showed that the addition of Con A did not disorganize the microtubules but the addition of colchicine did. The increase in beta-tubulin mRNA expression which was observed after cell culture and after stimulation by dB-cAMP was suppressed by the addition of Con A. Con A did not affect the beta-tubulin mRNA expression when the cells had already been cultured, while colchicine drastically decreased it. Thus, Con A appeared to affect the beta-tubulin mRNA expression in a different manner from colchicine, probably through inhibition of cell movement.
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PMID:Concanavalin A affects beta-tubulin mRNA expression during neuritic processes of mouse neuroblastoma N18TG2 cells in a different manner from colchicine. 215 31

The phosphorylation of rat brain microtubule protein on intracranial injection of labeled phosphate has been analyzed. The major microtubule protein components phosphorylated in vivo in rat brain are the high-molecular-weight microtubule-associated proteins (MAPs) MAP-1A, MAP-1B, and MAP-2. A slight phospholabeling of beta-tubulin, which corresponds to the phosphorylation of a minor neuronal beta-tubulin isotype, is also observed. Whereas MAP-1B, MAP-2, and beta-tubulin are phosphorylated in the brain of 5-day-old rat pups, when most neurons of the CNS are extending processes, MAP-1A phosphorylation is observed only after neuronal maturation takes place. The phosphorylation of MAP-1A, MAP-1B, and beta-tubulin may be due mainly to casein kinase II or a related enzyme, whereas MAP-2 appears to be modified by other enzymes such as the cyclic AMP-dependent protein kinase (protein kinase A) and the calcium/phospholipid-dependent protein kinase (protein kinase C). Microtubule protein phosphorylation has also been studied in neuronal cultures. In differentiated neuroblastoma cells, only MAP-1B and beta-tubulin are phosphorylated in a manner coupled to neurite outgrowth. In primary cultures of fetal rat brain neurons, the pattern of microtubule protein phosphorylation resembles that found in vivo in rat pup brain. As phosphorylated MAP-1A and MAP-1B are present mainly on assembled microtubules, whereas the phosphorylation of MAP-2 decreases its interaction with microtubules, a role can be suggested for the phosphorylation of these proteins in the regulation of microtubule assembly and disassembly during neuronal development.
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PMID:Phosphorylation of microtubule proteins in rat brain at different developmental stages: comparison with that found in neuronal cultures. 229 11

Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in the treated cells and appeared similar to what was seen histochemically. Reduced and oxidized glutathione levels suggest that methylmercury may manifest its deleterious effects via oxidation of tubulin sulfhydryls, and by alterations due to peroxidative injury. Cells exposed to methylmercury showed a decrease in glutathione peroxidase activity. Simultaneous administration of 10 mM glutathione with 2.5 and 5.0 microM methylmercury dramatically prevented cell injury.
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PMID:The protective effects of glutathione against methylmercury cytotoxicity. 231 60

Neurotrophic factors may increase axon and dendrite growth in part by regulating the content of cytoskeletal elements such as microtubules, which are comprised of tubulin subunits. The mechanism by which insulin, insulin-like growth factors (IGFs), and nerve growth factor (NGF) can increase the relative abundance of tubulin mRNAs as a prelude to neurite formation was studied. Insulin significantly increased the abundance of tubulin mRNAs relative to total RNA in cultured human neuroblastoma SH-SY5Y cells. This increase was not the result of a generalized elevation of all transcripts, because tubulin mRNAs were elevated relative to poly(A)+ RNA as well. Moreover, whereas polymerases I and III were elevated in activity, polymerase II was not. Tubulin mRNAs were stabilized against degradation in the presence of actinomycin D by both insulin and IGF-I. In contrast, actin and histone 3.3 mRNAs were neither increased nor stabilized. Insulin did not alter alpha- or beta-tubulin gene transcription rates in nuclear run-off experiments, and did increase the relative synthesis of tubulin proteins. These results suggest that tubulin mRNA levels are increased mainly through selective stabilization by insulin and IGFs. Because NGF is known to stabilize tubulin mRNA levels also, stabilization of tubulin mRNAs is suggested to be a common event in the pathway leading to neurite elongation directed by neuritogenic polypeptides.
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PMID:Stabilization of tubulin mRNAs by insulin and insulin-like growth factor I during neurite formation. 269 75

Posttranslational modifications of tubulin were analyzed in mouse brain neurons and glia developing in culture. Purified tubulin was resolved by isoelectric focusing. After 3 weeks of culture, neurons were shown to express a high degree of tubulin heterogeneity (8 alpha and 10 beta isoforms), similar to that found in the brain at the same developmental stage. Astroglial tubulin exhibits a less complex pattern consisting of 4 alpha and 4 beta isoforms. After incubation of neuronal and glial cells with 3H-acetate in the presence of cycloheximide, a major posttranslational label was found associated with alpha-tubulin and a minor one with beta-tubulin. The acetate-labeled isotubulins of neurons were resolved by isoelectric focusing into as many as 6 alpha and 7 beta isoforms, while those of astroglia were resolved into only 2 alpha and 2 beta isoforms. The same alpha isoforms were also shown to react with a monoclonal antibody recognizing selectively the acetylated form(s) of alpha-tubulin. Whether acetate-labeling of alpha-tubulin in these cells corresponds to the acetylation of Lys40, as reported for Chlamydomonas reinhardtii, is discussed according to very recent data obtained by protein sequence analysis. Tubulin phosphorylation was analyzed by incubation of cell cultures with 32PO4. No phosphorylation of alpha-tubulin isoforms was detected. A single beta-tubulin isoform (beta'2), expressed only in neurons, was found to be phosphorylated. This isoform is similar to that previously identified in differentiated mouse neuroblastoma cells.
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PMID:Posttranslational modifications of tubulin in cultured mouse brain neurons and astroglia. 273 26

We have examined the phosphorylation of cellular microtubule proteins during differentiation and neurite outgrowth in N115 mouse neuroblastoma cells. N115 differentiation, induced by serum withdrawal, is accompanied by a fourfold increase in phosphorylation of a 54,000-mol-wt protein identified as a specific isoform of beta-tubulin by SDS PAGE, two-dimensional isoelectric focusing/SDS PAGE, and immunoprecipitation with a specific monoclonal antiserum. Isoelectric focusing/SDS PAGE of [35S]methionine-labeled cell extracts revealed that the phosphorylated isoform of beta-tubulin, termed beta 2, is one of three isoforms detected in differentiated N115 cells, and is diminished in amounts in the undifferentiated cells. Taxol, a drug which promotes microtubule assembly, stimulates phosphorylation of beta-tubulin in both differentiated and undifferentiated N115 cells. In contrast, treatment of differentiated cells with either colcemid or nocodazole causes a rapid decrease in beta-tubulin phosphorylation. Thus, the phosphorylation of beta-tubulin in N115 cells is coupled to the levels of cellular microtubules. The observed increase in beta-tubulin phosphorylation during differentiation then reflects developmental regulation of microtubule assembly during neurite outgrowth, rather than developmental regulation of a tubulin kinase activity.
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PMID:A polymer-dependent increase in phosphorylation of beta-tubulin accompanies differentiation of a mouse neuroblastoma cell line. 285 24


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