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)

Proteoglycans (PGs) may play a fundamental role in all forms of amyloidosis. In Alzheimer's disease, proteoglycans are found deposited in senile plaques and in neurofibrillary tangles. However, the cellular source of these deposited PGs and their role in amyloidosis in Alzheimer's disease is unknown. Proteoglycans were purified from conditioned medium of human neuroblastoma cells (SKNSH-SY 5Y). Two species of proteoglycans were identified by enzyme susceptibility including a heparan sulfate proteoglycan and a dermatan sulfate proteoglycan. A monoclonal antibody to the protein core of a vascular basement membrane heparan sulfate proteoglycan found in senile plaques in Alzheimer's disease cross-reacted with the proteoglycans secreted by human neuroblastoma cells. Binding between 35SO4-labelled neuroblastoma proteoglycans and the Alzheimer amyloid (A4) peptide was demonstrated by affinity chromatography. Specificity studies demonstrated that binding of human neuroblastoma proteoglycans to the amyloid peptide was specific for a heparan sulfate glycosaminoglycan, with some binding to a dermatan sulfate proteoglycan. Binding to A4 was also demonstrated by a chemically deglycosylated protein core preparation. No significant binding of neuroblastoma proteoglycans was found to two other basic peptides derived from the extracellular domain of the beta-amyloid precursor, demonstrating the specificity of proteoglycan binding to the A4 peptide. Human neuroblastoma proteoglycans may bind to the-Alzheimer amyloid A4 peptide in a region with a heparin binding consensus sequence [VHHQKL] which also contains the cleavage site of the beta-amyloid precursor protein. Neuronal proteoglycans may either regulate the secretion of the amyloid protein precursor or modify the binding of the amyloid protein precursor to other cellular adhesion molecules. Alterations in this binding may be related to the pathogenesis of amyloid deposition in Alzheimer's disease.
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PMID:Binding of secreted human neuroblastoma proteoglycans to the Alzheimer's amyloid A4 peptide. 843 62

In cultured mouse neuroblastoma N1E-115 cells, inorganic lead (Pb2+) affects inward currents induced by activation of neuronal type nicotinic acetylcholine receptors (nAChR) in a biphasic manner. At nanomolar concentrations a blocking action is observed, while at submillimolar concentrations this blocking effect is reversed, resulting in a U-shaped concentration-effect curve. Maximal block by 90% is observed at 1-3 microM Pb2+. The interactions of Pb2+ with nAChR were examined at the blocking concentration of 10 nM Pb2+ and at 10 microM Pb2+, presenting the reversal of block. The fitted Emax for nAChR receptor activation by ACh was attenuated at both high and low Pb2+ concentrations by 24% and 54%, respectively. The EC50 values of the activation curves were not significantly altered; amounting to 53 microM, 64 microM and 86 microM ACh in the control situation and in the presence of 10 nM and 10 microM Pb2+, respectively. Further, receptor desensitization and ion channel block by ACh were also not affected by Pb2+. The results indicate that Pb2+ affects nAChR in a dual manner that involves inhibition and potentiation, both by non-competitive interactions. Neuronal nAChR expressed in N1E-115 cells resemble a combination of alpha 4 and beta 2 subunits, that constitute the predominant subunits in the central nervous system. The differential inhibition and potentiation of nAChR, together with the high sensitivity, are of interest with respect to Pb2+ neurotoxicity.
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PMID:Dual, non-competitive interaction of lead with neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells. 904 21

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.
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PMID:Novel perspectives on pituitary and brain angiotensinogen. 910 Dec 59

The metastatic potential of undifferentiated neuroblastomas is typically lost when differentiation into ganglioneuroblastomas occurs spontaneously or is induced. Cell adhesion may play a role in metastasis, and we have shown recently that expression of integrin alpha v beta 5 protein and mRNA is up-regulated in ganglioneuroblastomas in vivo. To investigate whether interactions of alpha v beta 5 with matrix components play a role in the loss of metastatic potential, we used immunohistochemical and in situ hybridization to analyze neuroblastic tumors at various stages of differentiation for expression of the alpha v beta 5 ligands, vitronectin and osteopontin, and determined the ability of vitronectin to promote attachment and neurite outgrowth in vitro in a retinoic-acid-differentiated neuroblastoma cell model. We found that vitronectin, but not osteopontin, was expressed in 5 of 5 ganglioneuroblastomas but was absent or weakly expressed in 6 of 6 undifferentiated neuroblastomas. Neuronal cell vitronectin was detected in 7 of 9 ganglioneuromas, 5 of 8 peripheral ganglia, and 14 of 21 adrenal gland medullae, confirming expression of vitronectin in mature peripheral neurons. In vitro, vitronectin promoted attachment of both undifferentiated and retinoic-acid-differentiated neuroblastoma cells, which was inhibited 20 and 60%, respectively, by monoclonal antibody anti-integrin alpha v beta 5. Vitronectin-promoted neurite outgrowth of retinoic-acid-differentiated neuroblastoma cells was not inhibited by monoclonal antibody anti-alpha v beta 5. These data suggest that the synthesis of vitronectin and the ability of integrin alpha v beta 5 to mediate vitronectin adhesion on retinoic-acid-differentiated neuroblastoma cells may promote differentiation of neuroblastoma cells in vivo.
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PMID:Vitronectin expression in differentiating neuroblastic tumors: integrin alpha v beta 5 mediates vitronectin-dependent adhesion of retinoic-acid-differentiated neuroblastoma cells. 913 89

A role in neuronal homeostasis is suggested by the persistent expression of the insulin-like growth factors in the adult nervous system. SH-SY5Y human neuroblastoma cells, a well-characterized in vitro model of human neurons, were used to investigate the effects of hyperosmotic stress on neurons. Neuronal DNA fragmentation was detected within 1 h and pyknotic nuclei were apparent in attached cells after 12 h of hyperosmotic stress. In parallel, flow cytometry measurements revealed a sudden increase in the rate of cells irreversibly undergoing programmed cell death after 12 h of hyperosmotic exposure. Insulin-like growth factor-I delayed the onset of a laddered DNA fragmentation pattern for 24 h and provided continuing protection against hyperosmotic exposure for 72 h. Amino acid uptake was decreased in hyperosmotic medium even in the presence of insulin-like growth factor-I; the protein synthesis inhibitor cycloheximide neither prevented the induction of programmed cell death nor interfered with the ability of insulin-like growth factor-I to act as an osmoprotectant in hyperosmotic medium. Cysteine and serine protease inhibitors each prevented DNA fragmentation under hyperosmotic conditions, suggesting that the osmoprotectant activity of insulin-like growth factor-I involves the suppression of protease activity. Collectively, these results indicate that insulin-like growth factor-I limits the death of neurons under stressful environmental conditions, suggesting that it may provide a candidate therapy in the treatment of hyperosmolar coupled neurological injury.
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PMID:Insulin-like growth factor-I is an osmoprotectant in human neuroblastoma cells. 920 Jul 35

We have tested the hypothesis that hippocampal neurons respond to thrombin via a neuronal thrombin receptor. A human neuroblastoma cell line, SK-N-SH, known to be thrombin responsive morphologically, responded both to thrombin and thrombin receptor agonist peptide (TRAP 42-55) with elevation of intracellular calcium. In Western blots of membranes from SK-N-SH cells and cultured rat hippocampal neurons using an antibody against the N-terminal peptide of the human thrombin receptor, putative receptor proteins of 66 and 47 kDa were detected in both cells. Neurons were treated with thrombin and TRAP 42-55 (TRAP-14) to determine their effects on intracellular levels of calcium and cAMP. Only 10% of the neurons showed a rapid response to thrombin, but most responded rapidly to agonist peptide with a prolonged elevation of intracellular free calcium. Neuronal cAMP levels were decreased by 40% after 24 h thrombin treatment. This decrease in cAMP level could be blocked by both the Gi-protein inhibitor, pertussis toxin, and the thrombin inhibitor, hirudin, suggesting a possible involvement of Gi-protein-coupled receptor activation. Furthermore, rapid calcium and cAMP responses were apparently induced by pre-treatment of neurons with thrombin for 24 h and subsequent washout. In summary, these data indicate that rat primary hippocampal neurons have thrombin receptors whose responses to thrombin apparently are up-regulated by 24 h thrombin pre-treatment. These results may have implications for synaptic remodeling, learning and memory.
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PMID:Thrombin receptor on rat primary hippocampal neurons: coupled calcium and cAMP responses. 924 61

The glial-derived neurotrophic protein S100beta has been implicated in the development and maintenance of the nervous system. S100beta has also been postulated to play a role in mechanisms of neuropathology because of its specific localization and selective overexpression in Alzheimer's disease. However, the exact relationship between S100beta overexpression and neurodegeneration is unclear. Recent data have demonstrated that treatment of cultured rat astrocytes with high concentrations of S100beta results in a potent activation of inducible nitric oxide synthase (iNOS) and a subsequent generation of nitric oxide (NO), which can lead to astrocytic cell death. To investigate whether S100beta-induced NO release from astroctyes might influence neurons, we studied S100beta effects on neuroblastoma B104 cells or primary hippocampal neurons co-cultured with astrocytes. We found that S100beta treatment of astrocyte-neuron co-cultures resulted in neuronal cell death by both necrosis and apoptosis. Neuronal cell death induced by S100beta required the presence of astrocytes and depended on activation of iNOS. Cell death correlated with the levels of NO and was blocked by a specific NOS inhibitor. Our data support the idea that overexpression of S100beta may be an exacerbating factor in the neurodegeneration of Alzheimer's disease.
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PMID:S100beta induces neuronal cell death through nitric oxide release from astrocytes. 937 60

Neuronal hybrid cells established by somatic cell fusion are useful for studies of neuronal properties at the molecular level (Hammond, D.N., Lee, H.J., Tonsgard, J.H. and Wainer, B.H., Development and characterization of clonal cell lines derived from septal cholinergic neurons, Brain Res., 512 (1990) 190-200; Wainwright, M.S., Perry, B.D., Won, L.A., O'Malley, K.L., Wang, W.Y., Ehrlich, M.E. and Heller, A., Immortalized murine strial neuronal cell lines expressing dopamine receptors and cholinergic properties, J. Neurosci., 15 (1995) 676-688). The somatic cell fusion method requires a fusion partner which is unable to survive in the selection medium if it does not fuse with primary cells to isolate the hybrid cells. Hypoxanthine guanine phosphoribosyltransferase (HPRT)-deficient partner cells and hypoxanthine, aminopterin and thymidine (HAT) selection medium are commonly used for this procedure (Harlow, E. and Lane, D. (Eds.), Antibodies: a Laboratory Manual, Cold Spring Harbor Laboratory Publications, New York, 1988, pp. 139-243). The present method requires neither HPRT-deficient cells nor HAT medium. Primary neurons are fused with the C1300 neuroblastoma cells pretreated with emetine (Grollman, A.P., Inhibitors of protein biosynthesis, J. Biol. Chem., 243 (1968) 4089-4094), an inhibitor of ribosomes and actinomycin D (Perry, R.P., Selective effects of actinomycin D on the intracellular distribution of RNA synthesis in tissue culture cells, Exp. Cell Res., 29 (1963) 400-406), an inhibitor of ribosomal RNA (rRNA) synthesis, before fusion. By this treatment, we are able to isolate hybrid cells after fusion because non-fused C1300 cells die due to the loss of active ribosomes and protein synthesis, whereas C1300 cells fusing with primary cells survive due to the supply of intact ribosomes and rRNA from primary cells. This method produces neuronal hybrids at high efficiency.
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PMID:Method for production of neuronal hybridoma using emetine and actinomycin D. 938 57

Neuronal-type nitric oxide synthase (NOS I) is involved in ischemia-induced brain damage, and glucocorticoids have been reported to protect from brain damage. This prompted us to investigate if the activity or expression of NOS I was influenced by glucocorticoids. We used the murine neuroblastoma cell line N1E-115 as our experimental model. Short-term incubation (30 min) of the N1E-115 cells with dexamethasone (10 nM to 1 microM) or hydrocortisone (100 nM to 10 microM) did not change the enzymatic activity of NOS I. However, the glucocorticoids inhibited NOS I mRNA expression in a concentration-dependent fashion (down to 53.3 +/- 2. 5% of control). In time-course experiments with 100 nM dexamethasone, maximum down-regulation of NOS I mRNA was seen after 24 hr (55.6 +/- 6.3% of control). Similar effects were seen with 10 microM hydrocortisone. The effect of 100 nM dexamethasone was completely reversed by 1 microM of the glucocorticoid receptor antagonist mifepristone. In experiments with actinomycin D (10 microg/ml), the half-life of the NOS I mRNA was determined to be approximately 12 hr and remained unchanged after glucocorticoid incubation. Nuclear run-on analyses indicated that the decrease in NOS I mRNA was the result of a glucocorticoid-induced inhibition of NOS I gene transcription. In Western blots, the 160-kDa NOS I protein band was down-regulated to 68.5 +/- 8.4% of control after an incubation of the N1E-115 cells with 100 nM dexamethasone for 26 hr. Similarly, NO production was down-regulated to 57.8 +/- 8.7% of control. These data demonstrate that glucocorticoids reduce the expression of NOS I without changing its activity.
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PMID:Expressional down-regulation of neuronal-type nitric oxide synthase I by glucocorticoids in N1E-115 neuroblastoma cells. 968 66

The cyclin-dependent kinase 5 (Cdk5) catalytic subunit is expressed in both cycling and noncycling cells and is present in many tissues. Neuronal and muscle cells contain the highest amount of this protein. The p35 protein, which is expressed solely in the brain, activates Cdk5. Cdk5 activity is involved in terminal differentiation of neurons and muscle cells. We attempted to clone cdk5 by PCR from a human fetal brain cDNA library. Surprisingly, we amplified two forms of the cdk5 gene, the wild type and a cdk5 variant that lacks the complete kinase domain VI. The variant is also found in SH-SY-5Y neuroblastoma cells but not in T-cells, HeLa cells, the thymus, and placental tissue. The protein encoded by the cdk5 variant, the Cdk5 isoform (Cdk5i), purifies with p35 when coexpressed in insect cells. The activity associated with the heterodimer Cdk5i/p35 is found to be appreciably weaker than the wild-type Cdk5/p35 kinase. Moreover, Cdk5i/p35 cannot autophosphorylate its two subunits as with Cdk5/p35. Interestingly, kinase-defective Cdk5i can abolish the activity of wild-type Cdk5 when both are coexpressed with p35 in insect cells, suggesting that Cdk5i may have a function in regulating Cdk5 activity in human cells too.
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PMID:Identification of a human cDNA encoding a kinase-defective cdk5 isoform. 987 33


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