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 recently reported presence of alumino-silicates in the core of Alzheimer's senile plaques raises a number of questions concerning the little studied area of interactions between solid particles and neuronal tissue. In this preliminary study we report that contact between crystalline alumino-silicates and cultured neuroblastoma cells selectively caused a rapid increase in membrane electrical conductance and loss of excitable activity. Severe morphological deterioration was subsequently evident within 30 min of exposure. Similar effects were induced by a magnesium silicate mineral but not by aluminum hydroxides or by silicon in the form of quartz. Homogeneously charged synthetic particles did not induce changes in electrical function of the cells. These results suggest that a layout incorporating both negative and positive charges, as can be found on the broken edges of platy clay metallo-silicates, and the non-isodiametrical geometry of the particles may be necessary for the acute neurotoxic interaction observed.
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PMID:Toxic effects of alumino-silicates on nerve cells. 208 76

Alternative splicing of the transcript encoding the beta-amyloid precursor protein (BAPP) of Alzheimer's disease produces multiple mRNA species. Translation of these mRNAs predicts protein products of 770, 751, and 695 amino acids. The difference arises from the inclusion in BAPP-770/751 of a 56-residue insert region which is homologous to Kunitz-type protease inhibitors. We have prepared and affinity-purified anti-peptide antibodies that react specifically with either BAPP-770/751 (insert-specific) or BAPP-695 (junction-specific). A detectable level of the mRNA corresponding to the BAPP-770/751 protein was found in all cell lines tested. Immunoprecipitation of 35S-labeled proteins from these cell lines showed them to contain one or two Mr 105,000 bands reactive with the insert-specific serum, i-291. In contrast, only cos-7 cells and the human neuroblastoma cell line, IMR-32, contained mRNA species that encode the BAPP-695 protein, as shown by Northern analysis with a junction-spanning oligonucleotide probe. A band of Mr 95,000 was immunoprecipitated specifically from these two cell lines using the junction-specific serum, J-284. Indirect immunofluorescence labeling of cells corroborated these findings. All cells reacted with the insert-specific antibodies, i-291 and i-324. Only cos-7 and IMR-32 cells reacted with the junction-specific antibody, J-284. These results demonstrate the usefulness of anti-peptide antibodies for the differential detection of the BAPP-695 and BAPP-770/751 proteins.
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PMID:Characterization of beta-amyloid precursor proteins with or without the protease-inhibitor domain using anti-peptide antibodies. 211 83

Studies were undertaken on the processing of Alzheimer's disease-associated beta-amyloid precursor protein in normal cultured human fibroblasts and a human neuroblastoma cell line. Major differences in processing between the secreted and intracellular forms of the precursor were found. The intracellular form appears to undergo amino-terminal processing yielding many smaller fragments, whereas the secreted form does not show any further proteolytic cleavage after its release from the cell surface. In pulse-chase experiments, antibodies to the A4 region immunoprecipitated bands of Mr = 92,000-128,000, which represent the intact precursor; several smaller intracellular fragments of Mr = 70,000-72,000, 55,000, 33,000 and 6,000 also immunoprecipitated with this antibody. The Mr = 6,000 band cleared from the cell very quickly and is postulated to be the A4-carrying remnant of the secreted protein. The data show that a fragment of Mr = 33,000, which includes the A4 region, is one stable processed end-product of the intracellular precursor protein. It is possible that different posttranslational modifications are the signals responsible for the differences in processing between the secreted and intracellular amyloid precursor protein.
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PMID:Processing of Alzheimer's disease-associated beta-amyloid precursor protein. 212 35

Retinoic acid (RA) induced differentiation of SH-SY5Y neuroblastoma cells is associated with more than a tenfold induction of total Alzheimer's disease beta A4 amyloid protein precursor (APP) mRNA as analyzed by Northern blot hybridisation. S1 nuclease protection experiments reveal that the splicing pattern of these differentiated cells is altered in favor of APP695 mRNA, coding for the shortest amyloidogenic beta A4 amyloid precursor protein. Induction of differentiation of SH-SY5Y cells with NGF leads to a fivefold increase of total APP mRNA without change in the splicing pattern. This suggests that RA but not NGF induces factor(s) which are responsible for an APP hnRNA splicing favoring APP695 mRNA.
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PMID:Retinoic acid induced differentiated neuroblastoma cells show increased expression of the beta A4 amyloid gene of Alzheimer's disease and an altered splicing pattern. 220 13

A baculovirus expression vector, which contains the coding sequences for human prepro (beta) nerve growth factor under control of the viral polyhedrin promoter, was constructed. Upon infection of insect cells with the recombinant virus, mature human beta nerve growth factor (rhNGF) was released into the culture fluid. The mature rhNGF was biologically active since rat pheochromocytoma (PC12) and human neuroblastoma (SH-SY5Y) cells were induced to extend neurites upon treatment with this material. This activity was abolished by treating with antiserum prepared against mature mouse beta NGF (mNGF). When compared with mNGF, rhNGF more rapidly elicited the differentiation response in both PC12 and SH-SY5Y cells. In an in vivo assay of cholinergic cell survival, rhNGF was nearly as potent as mNGF in protecting cholinergic neurons from degeneration following a fimbria-fornix lesion. These results show that the baculovirus expression system provides quantities of biologically potent human beta NGF suitable for a comprehensive program of research to ascertain beta NGF's potential as a therapeutic agent for the treatment of Alzheimer's disease.
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PMID:Human beta nerve growth factor obtained from a baculovirus expression system has potent in vitro and in vivo neurotrophic activity. 220 79

A pool of ten monoclonal antibodies to SDS-insoluble epitopes of Alzheimer neurofibrillary tangles (NFT) was used to screen an adult human brain cDNA expression library. Fourteen clones were isolated, two of which are described. The largest of the clones encodes 80 kD, or approximately 600 amino acids, of microtubule-associated protein 2 (MAP 2). The MAP 2 region encoded by the clone shares at least two epitopes with human tau, another microtubule-associated protein which cross-reacts with NFT. In rat brain mRNA, the MAP 2 cDNA hybridizes to a single transcript of 9.5 kb. In human neuroblastoma mRNA, the MAP 2 cDNA hybridizes, at high stringency, to two transcripts of 9.5 kb and 6 kb. The 6-kb transcript comigrates with the transcript for tau, as detected by a human tau cDNA. The properties of the MAP 2 cDNA suggest that, in humans, MAP 2 and tau have a common domain which may play a role in NFT formation. Another clone isolated with the anti-NFT antibodies shares epitopes, but not nucleic acid homology, with the MAP 2 cDNA. This clone detects a single abundant transcript of 1 kb present in RNA from human neuroblastoma and from several non-neuronal human cell lines. The properties of this cDNA suggest that it encodes a protein other than those previously reported to cross-react with NFT.
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PMID:Isolation and characterization of cDNA clones encoding epitopes shared with Alzheimer neurofibrillary tangles. 244 45

Protease nexin-II (PN-II) is a protease inhibitor that forms SDS-resistant inhibitory complexes with the epidermal growth factor (EGF)-binding protein, the gamma-subunit of nerve growth factor, and trypsin. The properties of PN-II indicate that it has a role in the regulation of certain proteases in the extracellular environment. Here we describe more of the amino-acid sequence of PN-II and its identity to the deduced sequence of the amyloid beta-protein precursor (APP). Amyloid beta-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome. A monoclonal antibody against PN-II (designated mAbP2-1) recognized PN-II in immunoblots of serum-free culture medium from human glioblastoma cells and neuroblastoma cells, as well as in homogenates of normal and Alzheimer's disease brains. In addition, mAbP2-1 stained neuritic plaques in Alzheimer's disease brain. PN-II was a potent inhibitor of chymotrypsin with an inhibition constant Ki of 6 x 10(-10)M. Together, these data demonstrate that PN-II and APP are probably the same protein. The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolysis in the pathogenesis of Alzheimer's disease.
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PMID:Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor. 250 28

Multiple EBV-transformed B cell lines were established from five patients with a clinical diagnosis of Alzheimer's disease (AD) and six age-matched controls. The supernatants were screened for antibody activity against SDS-treated isolated neurofibrillary tangles (NFT). Reactive supernatants were identified from both the AD and control group. The frequencies of anti-NFT antibody-secreting lines were 6.3 and 1.6% for the AD and the control groups, respectively. A proportion of these supernatants also stained NFT in situ and neurons and/or glia in sections of the frontal and the temporal cortexes of autopsied AD and normal brains, as well as cells from three cell lines (HeLa, fibroblast, and neuroblastoma). Several patterns of staining were revealed by these supernatants, indicating different reactive antigens. One supernatant stained NFT and astrocytes in sections from AD brains. It did not stain sections from two normal brains. This cell line is the result of the immortalization of a circulating B cell making antibody specific for an antigen in AD. The present approach may provide new insights in the pathogenesis of AD.
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PMID:Autoantibodies to neurofibrillary tangles and brain tissue in Alzheimer's disease. Establishment of Epstein-Barr virus-transformed antibody-producing cell lines. 302 32

Multiple B cell lines established by Epstein-Barr viral transformation from six patients with Alzheimer's disease (AD) and six age-matched controls were screened immunocytochemically for their reactivities with AD and normal brains as well as to cell lines such as HeLa, fibroblasts and neuroblastoma. A higher incidence of reactivity with neurofibrillary tangles in situ was found among the cell lines from AD patients (23/866) in comparison with those from normals (6/803). Three cell lines from a patient with a definitive neuropathological diagnosis of AD were shown to secrete antibodies preferentially reactive with astrocytes in the grey matter of AD brain and one cell line from a normal elderly individual was shown to specifically react with neurofibrillary tangles and plaque neurites. These four antibodies were not reactive with normal brains or cell lines. These unique human antibodies may be useful in the diagnosis of AD and offer clues to its pathogenesis.
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PMID:Human antibodies to neurofibrillary tangles and astrocytes in Alzheimer's disease. 326 Sep 6

It has been hypothesized that the selective vulnerability of certain brain cholinergic neurons in Alzheimer's disease may reflect the unique way that choline is utilized by these neurons, i.e. not only as a component of major membrane phospholipids, e.g. phosphatidylcholine (PC), but also as a precursor of their neurotransmitter, acetylcholine (ACh). A prolonged utilization of choline liberated from PC, for ACh production, without adequate resynthesis of this lipid, might result in a net loss of the phosphatide followed by an impairment of membrane function and loss of cellular viability. Studies described in this paper, performed on electrically stimulated striatal slices and on cholinergic cell lines, test this hypothesis. 1) Electrically-stimulated striatal slices continue to release ACh, and sustain their free choline and ACh levels, even when perfused with a choline-free medium. Striatal levels of PC decline under these circumstances, and this decline can be blocked by adding tetrodotoxin (which blocks neuronal depolarization) or choline to the medium. The other major membrane phospholipids, phosphatidylserine and phosphatidylethanolamine, also decline proportionately to PC when slices are stimulated in the absence of choline. 2) In a population of purely cholinergic cells (human neuroblastoma, LA-N-2), ACh can be synthesized from choline derived from degradation of endogenous PC formed de novo by methylation of phosphatidylethanolamine. 3) PC content of cells in culture (neuroblastoma X glioma hybrid, NG 108-15) can be altered by adding various amounts of choline to the growth media. The proportion of PC in the cells apparently affects cellular survival and rate of growth. Taken together these data demonstrate that cholinergic neurons utilize the choline stored in PC to synthesize ACh; that this process may lead to a depletion in membrane phospholipids (when choline supply is inadequate); and that the resulting changes in neuronal membrane composition might adversely affect cellular viability.
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PMID:Phosphatidylcholine as a precursor of choline for acetylcholine synthesis. 331 98


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