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)

NEURO-2A neuroblastoma cells were differentiated by the addition of dibutyryl-cyclic AMP, resulting in an increase in transcription of mRNA coding for the two neurofilament polypeptides NF-L and NF-M. The mRNAs for these two polypeptides appeared to be co-expressed with both being switched on at 24 h after the addition of drug. This was in contrast to NF-H whose induction was only seen at 60 h following addition of drug. These results are in good agreement with the expression time course previously reported in-vivo and suggest that the neurofilament triplet polypeptides can be divided into two subsets which appear to be under different genetic control mechanisms according to their time course of expression.
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PMID:Temporal expression of neurofilament polypeptides in differentiating neuroblastoma cells. 166 92

A human neuroblastoma cell line, GOTO, extends neurite-like processes upon withdrawal of serum from culture medium. This morphological change was accompanied by a 5-fold increase in the neurofilament (NF)-L and a 10-fold increase in the NF-M mRNA levels after 24 h. The addition of a protein kinase inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) also induced the extension of neurite-like processes; however, it did not increase the NF mRNA levels. Thrombin inhibited the extension of neurite-like processes in serum-free culture without affecting the increase in the NF mRNA levels. There was no difference in the number of cells progressing through the S phase between serum-containing and -free cultures at 24 h. This indicates that the increase in the NF mRNA levels upon withdrawal of serum was not preceded by the growth arrest. Treatment with actinomycin D and cycloheximide inhibited the increase in the NF mRNA levels. The half life of the NF gene transcripts was prolonged in the serum-free condition. These results indicate that the serum depletion-induced increase in the NF-L and -M mRNA levels was regulated by both transcriptional and post-transcriptional mechanisms, and the increase in the expression of the NF genes was not simply mediated by growth arrest but controlled by unknown regulator proteins.
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PMID:Serum depletion increases the neurofilament protein mRNA levels in a neuroblastoma cell line, GOTO. 838 95

Two putative human oligodendroglioma cell lines were examined for the expression of the oligodendrocyte-associated genes, 2',3'-cyclic nucleotide-3'-phosphodiesterase, myelin basic protein, myelin proteolipid proteins, and myelin-associated glycoprotein. The expression of these genes also was examined in control astrocytoma and neuroblastoma cell lines. In addition, the expression of the non-oligodendrocyte-specific genes, glial fibrillary acidic protein (GFAP), neuron-specific enolase and neurofilaments (NF) NF-L and NF-M also were examined. All the cell lines expressed 2',3'-cyclic nucleotide 3'-phosphodiesterase, neuron-specific enolase, and vimentin, and none expressed myelin-associated glycoprotein. The "oligodendrocyte-specific" myelin proteolipid protein mRNAs and the "neuron-specific" NF-L mRNA were expressed in the two astrocytoma cell lines, which also expressed GFAP. Expression of intermediate filament protein genes was more restricted. The astrocytoma, neuroblastoma, and oligodendroglioma cell lines expressed only GFAP, NF-M, and cytokeratin K7, respectively. These results: (a) provide molecular data confirming the classification of the two cell lines as oligodendrogliomal and suggest that their molecular profiles are indicative of immature oligodendrocytes; (b) demonstrate the expression of cytokeratins in oligodendrogliomal cell lines and suggest that apparent GFAP expression in oligodendrogliomas detected by immunocytochemical methods may be due to cross-reactivity with cytokeratins, with which they share common polypeptide sequence; and (c) indicate that astrocytoma cell lines can exhibit a "mixed" phenotype, expressing genes associated with fully differentiated oligodendrocytes and neurons.
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PMID:Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas. 841 42

Neuroblastoma is a tumour derived from the sympathoadrenal progenitors of the neural crest. It is one of the most malignant solid tumours in childhood with an annual incidence of 9.4 per 10(6) children under 15 years of age. Recent studies suggest that immunocytological detection of neuroblastoma cells in bone marrow and circulating neuroblasts during treatment may predict clinical outcome and correlate with tumour relapse. The present methods of diagnosing metastasis in neuroblastoma include histological, biochemical and immunohistological analysis. Morphological distinction between tumour cells and primitive lymphoblasts in bone marrow is often difficult, and these methods may also not always be sensitive enough for early detection of the residual and minimally circulating tumor cells. A sensitive assay for detection of such residual cells using two tissue-specific markers, NFM and SYN, by reverse transcriptase-polymerase chain reaction (RT-PCR) is reported here. Analysis of the specificity of this assay in three neuroblastoma cell lines, namely IMR 32, SK-N-SH and SY5Y showed positive expression while control peripheral blood mononuclear cells (HL 60) were negative. In reconstituted cell spiking tests, this method has the ability to detect 1-10(3) neuroblastoma cell in 10(7) normal peripheral blood mononuclear cells (PBMC), as shown by serial dilution and limiting dilution. The NFM marker was found to be a more sensitive marker. The specificity and sensitivity of this technique makes it suitable for future application in detection of minimally disseminated tumour cells in neuroblastoma patients.
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PMID:Detection of low numbers of neuroblastoma cells in vitro. 939 1

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single injection of this compound (1.7 mg/kg, s.c.) produces delayed neurotoxicity (OPIDN) in hens in 7-14 days. Clinically, the disease is marked by hindlimb ataxia followed by paralysis after some time. A characteristic feature of this neuropathy is axonal swelling in the initial stages and comparative dissolution of the accumulated material and degeneration of distal axons with disease progression. Axonal swelling consists of aggregated neurofilaments, microtubules, and proliferated smooth endoplasmic reticulum. We studied expression of neurofilament (NF) mRNAs in brain regions and spinal cord to elucidate their role in OPIDN. There was a 50-200% increase in NF transcripts in 24 hr after DFP administration. The NF-L mRNA level started falling after 1-5 days and came down to control level in susceptible brain regions (i.e. cerebellum and brainstem) and spinal cord, but not in cerebral cortex, which does not show degeneration of axons in OPIDN. Cerebral cortex exhibited elevated levels of both NF-L and NF-M transcripts in DFP-treated hens throughout the period of observation. The induction of NF messages is consistent with the previously reported effect on extension of neurites of human neuroblastoma cells in culture. The transient increase in NF messages in susceptible tissues either may be responsible for the delayed degeneration of axons in OPIDN or is the result of interruption of regulatory signal due to progressive degeneration of axons.
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PMID:Enhanced mRNA expression of neurofilament subunits in the brain and spinal cord of diisopropyl phosphorofluoridate-treated hens. 1023 Jul 68

Cyclin-dependent kinase-5 (CDK-5) has been shown to play important roles in neuronal development and neurogenesis. In vitro studies indicate a role of CDK-5 in phosphorylation of neurofilaments (NFs). In this study, we have chosen the human neuroblastoma cell line SHSY5Y as a model system to study the in vivo phosphorylation of NF proteins by CDK-5. Upon differentiation of SHSY5Y cells with retinoic acid, we found that the phosphorylation of high molecular mass (NF-H) and medium molecular mass (NF-M) NFs increased, whereas the CDK-5 protein level and kinase activity were unaffected. The role of CDK-5 in the phosphorylation of cytoskeletal proteins was studied by using antisense oligonucleotides (ONs) to inhibit the expression of the CDK-5 gene. We found that inhibition of CDK-5 levels by antisense ON treatment resulted in a decrease in phosphorylation of NF-H that correlated with a decline in neurite outgrowth. These results demonstrate that CDK-5 is a major proline-directed kinase phosphorylating the human NF-H tail domain.
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PMID:CDK-5-mediated neurofilament phosphorylation in SHSY5Y human neuroblastoma cells. 1038 57

We examined cytoskeleton-associated forms of NF proteins during axonal neuritogenesis in cultured dorsal root ganglion (DRG) neurons and NB2a/d1 neuroblastoma. In addition to filamentous immunoreactivity, we observed punctate NF immunoreactivity throughout perikarya and neurites. Immuno-electron microscopy revealed this punctate immunoreactivity to consist of non-membrane-bound 75 nm round/ovoid structures consisting of amorphous, fibrous material. Endogenous and microinjected NF subunits incorporated into dots prior to their accumulation within filaments. A transfected GFP-conjugated NF-M incorporated into dots and translocated at a rate consistent with slow axonal transport in real-time video analyses. Some dots converted into a filamentous form or exuded filamentous material during transport. Dots contained conventional kinesin immunoreactivity, associated with microtubules, and their transport into axons was blocked by anti-kinesin antibodies and nocodazole. These oligomeric structures apparently represent one form in which NF subunits are transported in growing axons and may utilize kinesin as a transport motor.
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PMID:Kinesin-mediated transport of neurofilament protein oligomers in growing axons. 1052 15

2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of n-hexane, can structurally modify neurofilaments (NF) by pyrrole adduct formation and subsequent covalent cross-linking. 2,5-HD also induces accumulations of NF within the pre-terminal axon. We examined whether exposure of NF to 2,5-HD affected NF degradation. Two different models were used: (1) NF-enriched cytoskeletons isolated from human sciatic nerve were incubated with 2,5-HD in vitro and (2) differentiated human neuroblastoma cells (SK-N-SH) were exposed to 2, 5-HD in culture prior to isolation of cytoskeletal proteins. The cytoskeletal preparations were subsequently incubated with calpain II. The amount of NF-H and NF-L remaining after proteolysis was determined by SDS-PAGE and quantitative immunoblotting. NF-M proteolysis could not be quantified. Incubation of sciatic nerve cytoskeletal preparations with 2,5-HD resulted in cross-linking of all three NF proteins into high molecular weight (HMW) material with a range of molecular weights. Proteolysis of the NF-H and NF-L polypeptides was not affected by 2,5-HD-exposure. Degradation of the HMW material containing NF-H or NF-L was retarded when comparing with degradation of the NF-H and NF-L polypeptides, respectively, from control samples, but not as compared to the corresponding NF polypeptides from 2,5-HD-treated samples. Exposure of SK-N-SH cells to 2,5-HD also resulted in considerable cross-linking of NF. No differences were found between the proteolytic rates of NF-L and NF-H from exposed cells as compared with those subunits from control cells. Moreover, degradation of cross-linked NF-H was not different from monomeric NF-H. In conclusion, whether 2,5-HD affects calpain-mediated degradation of cross-linked NF proteins will depend on which model better reflects NF cross-linking as occurring in 2, 5-HD-induced axonopathy. However, with both models it was demonstrated that exposure of NF proteins to 2,5-HD without subsequent cross-linking is not adequate to inhibit NF proteolysis in vitro by added calpain.
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PMID:Effects of 2,5-hexanedione on calpain-mediated degradation of human neurofilaments in vitro. 1113 63

We investigated the role of neurofilament (NF) proteins in Alzheimer disease (AD) neurofibrillary degeneration. The levels and degree of phosphorylation of NF proteins in AD neocortex were determined by Western blots developed with a panel of phosphorylation-dependent NF antibodies. Levels of all three NF subunits and the degree of phosphorylation of NF-H and NF-M were significantly increased in AD as compared to Huntington disease brains used as control tissue. The increase in the levels of NF-H and NF-M was 1.7- and 1.5-fold (P<0.01) as determined by monoclonal antibody SMI33, and was 1.6-fold (P<0.01) in NF-L using antibody NR4. The phosphorylation of NF-H and NF-M in AD was increased respectively at the SMI31 epitope by 1.6- and 1.9-fold (P<0.05) and at the SMI33 epitope by 2.7- and 1.3-fold (P<0.01 and P<0.05). Essentially similar effects were observed in SY5Y human neuroblastoma cells when treated with okadaic acid, an inhibitor of protein phosphatase (PP)-2A and -1. This is the first biochemical evidence which unambiguously demonstrates the hyperphosphorylation and the accumulation of NF subunits in AD brain, and shows that the inhibition of PP-2A/PP-1 activities can lead to the hyperphosphorylation of NF-H and NF-M subunits.
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PMID:Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells. 1168 63

A human hybrid neuronal cell line A1 has been generated by somatic fusion between a human fetal cerebral neuron and a human neuroblastoma cell, and RT-PCR, immunochemical, and electrophysiological studies of the hybrid cells indicated that the cells express faithfully of morphological, immunochemical, physiological, and genetic features of human cerebral neurons. A1 hybrid neurons express neuron-specific markers such as neurofilament-L (NF-L), NF-M, NF-H, MAP-2, and beta tubulin III. A1 human hybrid neurons express messages for various cytokines and cytokine receptors which are similar to parental human CNS neurons and different from the other parental cell line, SK-SH-SY5Y neuroblastoma. A1 hybrid neurons also express messages for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and glutamic acid decarboxylase (GAD), indicating that they could differentiate into various subsets of neuronal types. Whole-cell patch clamp experiments showed that A1 hybrid neurons expressed Na+ currents, which were completely blocked by tetrodotoxin. In addition, depolarizing and hyperpolarizing voltage clamp steps evoked respective outward and inward K+ currents in these cells. When A1 hybrid neurons were exposed to beta amyloid for 72 hr, there was three-fold increase in TUNEL positive cells over controls, indicating that beta amyloid is neurotoxic to A1 hybrid neurons. The present study indicates that the A1 human hybrid neuronal cell line should serve as a valuable in vitro model for studies of biology, physiology, and pathology of human neurons in health and disease.
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PMID:Generation and characterization of human hybrid neurons produced between embryonic CNS neurons and neuroblastoma cells. 1246 May 57


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