SEARCH · Search PubMed

Results for “Neural cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1992

Use of the neural cell adhesion molecule VASE exon by neurons is associated with a specific down-regulation of neural cell adhesion molecule-dependent neurite outgrowth in the developing cerebellum and hippocampus.

The development of the CNS is associated with an increasing use of the 30-bp variable alternative, spliced exon (VASE) in neural cell adhesion molecule (NCAM). We have assessed the relative usage of VASE by reverse transcriptase-linked polymerase chain reaction in the developing cerebellum and hippocampus at times when neurons isolated from these tissues can respond to substrate-associated NCAM by increased axonal growth and also at later developmental stages, when they are no longer responsive to substrate-associated NCAM. Neurons isolated from the developing cerebellum at postnatal day 6 respond to NCAM with increased neurite growth. NCAM transcripts from these cells were found to have negligible levels of VASE usage. In contrast, neurons that are isolated at later stages of development (postnatal days 8, 10, and 11) and do not respond to NCAM were found to synthesise a much higher proportion of NCAM transcripts containing VASE. In the hippocampus, embryonic day 18 neurons, which are responsive to NCAM, express low levels of VASE, whereas postnatal days 4 and 5 neurons, which are not responsive to NCAM, have a greater proportion of transcripts containing VASE. Thus, the level of NCAM VASE exon usage by neurons appears to be a good indicator of the ability of these cells to respond to non-VASE-containing NCAM (expressed in a cellular substratum) by increased neurite outgrowth.

Alternative Splicing↗

PubMed1987

C6 glioma cells express modified neural-cell adhesion molecule-like glycoproteins.

We have studied the expression of neural-cell adhesion molecule (N-CAM)-like glycoproteins in a C6 glioma cell line. We found that: (a) C6 cells express N-CAM-like proteins on the cell surface, (b) the N-CAM-like proteins in C6 cells have apparent molecular weights of 130,000 and 150,000 kDa which are not seen in rodent brain and (c) deglycosylation of C6 N-CAMs suggest that the modifications are both in the carbohydrate and protein parts of the N-CAM. The expression of modified N-CAM glycoproteins is of interest in relation to the regulation of N-CAM expression.

Animals↗

PubMed2003

The human NTERA2 neural cell line generates neurons on growth under neural stem cell conditions and exhibits characteristics of radial glial cells.

NTERA2 cells are a human neural cell line generating neurons after exposure to retinoic acid and, as such, are widely used as a model of neurogenesis. We report that these cells form spheres when grown in serum-free medium supplemented with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). These spheres were found to express markers of radial glial cells such as, Pax6, glutamate transporter (GLAST), tenascin C, brain lipid-binding protein (BLBP), and the 3CB2 antigen. On plating on an adhesive substrate, NTERA2 spheres generate a large percentage of immature neurons (30-50%) together with a minority of cells of the oligodendrocyte lineage. Thus NTERA2 cells share properties with neural stem cells. However, at variance with the latter, we found that they produce their own bFGF implicated in an autocrine or paracrine proliferative loop and that they do not generate astrocytes after differentiation. These results provide an interesting model to study radial glial cells and their role in human neurogenesis.

Animals↗

PubMed2006

E Proteins and Id2 converge on p57Kip2 to regulate cell cycle in neural cells.

A precise balance between proliferation and differentiation must be maintained during neural development to obtain the correct proportion of differentiated cell types in the adult nervous system. The basic helix-loop-helix (bHLH) transcription factors known as E proteins and their natural inhibitors, the Id proteins, control the timing of differentiation and terminal exit from the cell cycle. Here we show that progression into S phase of human neuroblastoma cells is prevented by E proteins and promoted by Id2. Cyclin-dependent kinase inhibitors (CKI) have been identified as key effectors of cell cycle arrest in differentiating cells. However, p57Kip2 is the only CKI that is absolutely required for normal development. Through the use of global gene expression analysis in neuroblastoma cells engineered to acutely express the E protein E47 and Id2, we find that p57Kip2 is a target of E47. Consistent with the role of Id proteins, Id2 prevents activation of p57Kip2 expression, and the retinoblastoma tumor suppressor protein, a known Id2 inhibitor, counters this activity. The strong E47-mediated inhibition of entry into S phase is entirely reversed in cells in which expression of p57Kip2 is silenced by RNA interference. During brain development, expression of p57Kip2 is opposite that of Id2. Our findings identify p57Kip2 as a functionally relevant target recruited by bHLH transcription factors to induce cell cycle arrest in developing neuroblasts and suggest that deregulated expression of Id proteins may be an epigenetic mechanism to silence expression of this CKI in neural tumors.

Adenoviridae↗

PubMed1999

Transforming growth factor beta1-regulated cell proliferation and expression of neural cell adhesion molecule in B104 neuroblastoma cells: differential effects of ethanol.

The expression and activity of factors influencing early neuronal development are altered by ethanol. Such factors include growth factors, for example, platelet-derived growth factor and basic fibroblast growth factor (for cell proliferation), and cell adhesion molecules (for neuronal migration). One agent, transforming growth factor beta1 (TGFbeta1), may affect both events. We tested the hypothesis that ethanol alters myriad TGFbeta1-mediated activities [i.e., cell proliferation and neural cell adhesion molecule (N-CAM) expression] using B104 neuroblastoma cells. TGFbeta1 inhibited the proliferation of B104 cells as evidenced by decreases in cell number and [3H]thymidine ([3H]dT) incorporation. TGFbeta1 induced sustained activation of extracellular signal-regulated kinases (ERKs), which are part of the family of mitogen-activated protein kinases (MAPKs). Treatment with PD98059 (a MAPK kinase blocker) abolished TGFbeta1-regulated inhibition of [3H]dT incorporation. TGFbeta1-mediated growth inhibition was potentiated by ethanol exposure. Ethanol also produced prolonged activation of ERK, an effect that was partially eliminated by treatment with PD98059. On the other hand, TGFbeta1 up-regulated N-CAM expression, and this up-regulation was not affected by treatment with PD98059. Ethanol inhibited the TGFbeta1-induced up-regulation of N-CAM expression in a concentration-dependent manner. Thus, TGFbeta1 affects ERK-dependent cell proliferation and ERK-independent N-CAM expression in B104 cells. Both activities are sensitive to ethanol and may underlie the ethanol-induced alterations in the proliferation and migration of CNS neurons.

Animals↗

PubMed1994

Transfection of glioma cells with the neural-cell adhesion molecule NCAM: effect on glioma-cell invasion and growth in vivo.

The tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140-kDa isoform of the neural-cell adhesion molecule, NCAM. After s.c. injection, the NCAM-transfected cells showed a slower growth rate than the parent cell line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM-transfected cells, all animals developed neurological symptoms within 13-16 days. However, the tumors showed different growth characteristics. The NCAM-transfected BT4Cn cells were localized in the region of the injection site, with a sharply demarcated border between the tumor and brain tissue. In contrast, the parental cell line showed single-cell infiltration and more pronounced destruction of normal brain tissue. Using a 51Cr-release assay, spleen cells from rats transplanted with BT4Cn tumor cells generally showed a lower cytotoxic response than the spleen cells from rats transplanted with the transfected variants of BT4Cn cells, indicating that the transfection procedure in itself mediated an activation of the immune system. The present data suggest that NCAM may influence the malignant behavior of rat glioma cells in vivo.

Animals↗

PubMed2004

[Function of glial cell network as a modulator of neural cell death during retinal degeneration].

PURPOSE: Recent studies have demonstrated the mechanism of neural cell death, neuroprotection, and regeneration. However, the functional importance of glial cells during retinal degeneration is not well understood. In this review, we summarize our recent progress regarding the function of glial cells in neurotrophic factor production and neural cell death during retinal degeneration. METHODS: We made a rat model of photoreceptor degeneration by continuous light exposure, and examined the distribution and expression levels of neurotrophins and their receptors. In addition, we carried out quantitative analysis of neurotrophic factor production in cultured Müller glial cells and microglia. RESULTS: In the light-degenerated retina, microglia invade the photoreceptor layer from the inner part of the retina and increase the production of nerve growth factor (NGF). NGF decreases the production of basic fibroblast growth, factor, which prevents photoreceptor cell death, in Müller glial cells through low-affinity neurotrophin receptor p 75. Blockade of p 75 decreased photoreceptor cell death during light-induced retinal degeneration. CONCLUSIONS: These results suggest that a gliaglia network plays a critical role in neural cell death during retinal degeneration. Thus, a glia-glia network as well as a glia-neuron network could be a possible therapeutic target for inhibition of retinal degeneration.

Animals↗

PubMed1997

Appican expression induces morphological changes in C6 glioma cells and promotes adhesion of neural cells to the extracellular matrix.

Appicans are secreted or cell-associated brain chondroitin sulfate proteoglycans produced by glia cells and containing Alzheimer amyloid precursor protein (APP) as a core protein. Here, we report that rat C6 glioma cells transfected with appican displayed a dramatic change in their phenotypic appearance compared with untransfected cells or cells transfected with APP. Appican-transfected cells lost the round appearance of the untransfected control C6 cells, acquired a flat morphology, and elaborated more processes than control cells. Untransfected, or APP-transfected C6, cells were completely dissociated from their substrate after 40 min of treatment with cell dissociation solution. Under the same conditions, however, <20% of the appican-transfected C6 cells were dissociated from their substrate, suggesting that the appican-transfected glia cells attach more avidly to their substrate than do untransfected or APP transfected control cells. In contrast, appican-transfected fibroblast cells showed no morphological changes and dissociated from their substrate similarly to untransfected fibroblast cells. Extracellular matrix (ECM) prepared from appican-transfected C6 cell cultures contained high levels of appican and was a significantly better substrate for the attachment of C6 cells than ECM from either untransfected or APP-transfected cultures. Furthermore, cell adhesion to ECM was independent of the level of appican expression of the plated cells. ECM from appican-transfected C6 cultures stimulated adhesion of other neural cells including primary astrocytes, Neuro2a neuroblastoma, and PC12 pheochromocytoma, but not fibroblast cells. Conditioned media from appican-transfected C6 cultures failed to promote cell adhesion. Together, these data suggest that secreted appican incorporates into ECM and promotes adhesion of neural cells. Furthermore, our data suggest that the chondroitin sulfate chain engenders APP with novel biological functions.

Amyloid beta-Protein Precursor↗

PubMed1994

bcl-2 expression decreases methyl mercury-induced free-radical generation and cell killing in a neural cell line.

Methyl mercury neurotoxicity is associated with a broad range of neuropathologic and biochemical disturbances which include induction of oxidative injury. Treatment of the hypothalamic neural cell line GT1-7 with 10 microM methyl mercury (MeHg) for 3 h resulted in increased formation of reactive oxygen species (ROS), and decreased levels of reduced glutathione (GSH), associated with 20% cell death. Cells transfected with an expression construct for the anti-apoptotic proto-oncogene, bcl-2, displayed attenuated ROS induction and negligible cell death. Twenty-four-h exposure to 5 microM MeHg killed 56% of control cells, but only 19% of bcl-2-transfected cells. By using diethyl maleate to deplete cells of GSH, we demonstrate that the differential sensitivity to MeHg was not due solely to intrinsically different GSH levels. The data suggest that MeHg-mediated cell killing correlates more closely with ROS generation than with GSH levels and that bcl-2 protects MeHg-treated cells by suppressing ROS generation.

Animals↗

PubMed2003

Cellular signalling mechanisms of neural cell adhesion molecules.

Neural cell adhesion molecules of the immunoglobulin superfamily are multidomain proteins involved in important cellular events pertinent to development and adult neurological function. This review attempts to give a concise overview of the complex intracellular signaling pathways enabling neural cell adhesion molecules NCAM and L1 to regulate axon growth, guidance, and synaptic plasticity. Recent research findings suggest that these molecules signal in part through integrins leading to cytoskeletal rearrangements locally in the growth cone or cell leading edge, and to MAP kinase, which has the potential to cause gene expression changes in the nucleus. Abnormal expression of NCAM on human chromosome 11q23 has been linked to schizophrenia in humans, a multigenic disease believed to be of neurodevelopmental origin. L1 at Xq28 is the target for mutation in a complex mental retardation disorder termed the L1 syndrome (also sometimes referred to as CRASH syndrome). Thus a full understanding of the mechanism of NCAM and L1 function will contribute to understanding both normal brain development and pathologies associated with cognitive dysfunction in schizophrenia and mental retardation.

Animals↗

PubMed2006

Embryonic stem cells as a source of differentiated neural cells for pharmacological screens.

The process of bringing a new pharmacologically active drug to market is laborious, time consuming, and costly. From drug discovery to safety assessment, new methods are constantly sought to develop faster and more efficient procedures to eliminate drugs from further investigation because of their limited effectiveness or high toxicity. Because in vitro cell assays are an important arm of this discovery process, it is therefore somewhat unsurprising that there is an emerging contribution of embryonic stem (ES) cell technology to this area. This technology utilizes the in vitro differentiation of ES cells into somatic cell target populations that, when coupled to the use of "lineage selection" protocols, allows for the production of infinite numbers of pure populations of the desired cells for both bioactivity and toxicological screens. Unlike the use of transformed cell lines, ES-derived cells remain karyotypically normal and therefore better reflect the potential responses of cells in vivo, and when selected are more homogeneous than those obtained using primary cultures. In this chapter we discuss the use of ES cell-derived somatic cells in pharmacological screens, with particular emphasis on neural cells, and describe the methods and protocols associated with the development of ES cell-derived neural cell assays.

Animals↗

PubMed1977

Adhesion among neural cells of the chick embryo. II. Purification and characterization of a cell adhesion molecule from neural retina.

The aggregation of cells from dissociated neural retinas of chick embryos can be inhibited by antibodies prepared against whole retinal cells. In order to identify the antigens involved, substances released by retinal tissues in culture were tested for their ability to neutralize specifically the inhibition by antibody of cell adhesion. Using this assay, three active polypeptides from the culture supernatant were purified 500-fold by gel filtration and polyacrylamide gel electrophoresis. Rabbit antibodies prepared against these purified supernatant activities inhibited cell adhesion and reacted only with the three polypeptides. Immunoprecipitation by the specific antibodies of 3H-labeled proteins from a detergent extract of embryonic retinal cell membranes yielded a polypeptide having a Mr of 140,000 in sodium dodecyl sulfate. This precipitation was inhibited in the presence of the three culture supernatant polypeptides that had activity, suggesting that they contained antigenic determinants in common with the 140,000 Mr surface component. They therefore represent all or parts of this cell surface molecule that were released into solution during tissue culture. The data are consistent with the hypothesis that the 140,000 Mr polypeptide is intimately involved in initial adhesion among neural cells.

Animals↗

PubMed1990

Post-translation modifications of neural cell surface molecules.

Neural cells seem to express a relatively low number of adhesion molecules at their surface. The hypothesis of cell surface modulation postulates that a repertoire of specificities and binding affinities might result from alteration over time of the amount, distribution or chemical properties of a particular kind of molecules. We are describing two post-translational modifications; glycosylation and glypiation; which affect the neural cell adhesive molecule (N-CAM). We produced a monoclonal antibody recognizing only the highly sialyled of N-CAM and reported some of its applications. We also showed that N-CAM-120 is anchored to the membranes via a complex glycane-phosphatidylinositol.

Animals↗

PubMed2003

Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions.

Polysialic acid (PSA), a carbohydrate polymer attached to the neural cell adhesion molecule (NCAM), promotes neural plasticity and tumor malignancy, but its mode of action is controversial. Here we establish that PSA controls tumor cell growth and differentiation by interfering with NCAM signaling at cell-cell contacts. Interactions between cells with different PSA and NCAM expression profiles were initiated by enzymatic removal of PSA and by ectopic expression of NCAM or PSA-NCAM. Removal of PSA from the cell surface led to reduced proliferation and activated extracellular signal-regulated kinase (ERK), inducing enhanced survival and neuronal differentiation of neuroblastoma cells. Blocking with an NCAM-specific peptide prevented these effects. Combinatorial transinteraction studies with cells and membranes with different PSA and NCAM phenotypes revealed that heterophilic NCAM binding mimics the cellular responses to PSA removal. In conclusion, our data demonstrate that PSA masks heterophilic NCAM signals, having a direct impact on tumor cell growth. This provides a mechanism for how PSA may promote the genesis and progression of highly aggressive PSA-NCAM-positive tumors.

Apoptosis↗

PubMed1991

Induction of ICAM-1 on human neural cells and mechanisms of neutrophil-mediated injury.

To define mechanisms by which inflammatory cells damage neural tissue, the author investigated stimuli that promote leukocyte adherence and injury to cultured human cortical neuron (HCN-1) and neuroblastoma cells (LAN-1 and SK-N-SH). Neutrophils do not adhere to unstimulated neural cells but will bind to neural cells that have been exposed to tumor necrosis factor alpha (TNF alpha) and in some cases other cytokines such as gamma interferon (gamma IFN) or interleukin-1 (IL-1). Tumor necrosis factor alpha induces synthesis of intercellular adhesion molecule-1 (ICAM-1) mRNA and cell surface expression of ICAM-1 on cultured neural cells. Adherence of neutrophils to cytokine-stimulated neural cells is mediated primarily by ICAM-1:LFA-1 interactions, because 70% to 90% of the binding can be blocked by monoclonal antibodies to either ligand. Prior introduction of an oxidizable dye, 5-(and 6-)carboxy-2',7' dichlorofluorescin diacetate into the LAN-1 cells demonstrates that adherent neutrophils can release oxidizing radicals into the neural cell cytoplasm. These results suggest that cytokines released in the course of inflammation may induce expression of ICAM-1 on neurons, allowing them to be targeted by leukocytes expressing the appropriate receptors. The resulting adhesive interactions may facilitate introduction of various toxic agents into the neural cytoplasm.

Cell Adhesion↗

PubMed1989

Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule.

Neural cell adhesion molecule (N-CAM) is a membrane glycoprotein expressed on neural and muscle tissues that is involved in homotypic adhesive interactions. We have demonstrated that N-CAM also is expressed on hematopoietic cells, and is recognized by the anti-Leu-19 mAb. Leu-19 is preferentially expressed on NK cells and T lymphocytes that mediate MHC-unrestricted cytotoxicity, but is also present on some myeloid leukemia cell lines. On NK cells, T cells, the KG1a.5 hematopoietic cell line, and a neuroblastoma cell line, Leu-19 is a approximately 140-kD polypeptide with N-linked carbohydrates and abundant sialic acid residues. Sequential immunoprecipitation and peptide mapping demonstrated that the Leu-19 and N-CAM molecules expressed on leukocyte and neuroblastoma cell lines are similar structures. These findings suggest that the Leu-19 antigen on leukocytes may be involved in cell adhesion, analogous to the function on N-CAM on neural cells.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1994

New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM.

The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis, before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival, and expression of the ganglioside fucosyl-GM1 (FucGM1). Sera were considered positive if NCAM concentrations were higher than the mean concentration of healthy controls plus two standard deviations. Twenty-two percent of the sera from SCLC patients were positive for NCAM. No difference in concentration was found between SCLC patients with localized and extensive disease. Serum from one patient with cancer of the thyroid, but no sera from non-SCLC patients or normal healthy controls, was positive. The expression of NCAM did not correlate to any of the clinical parameters, and no correlation was found to the other serum marker, FucGM1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

Elimination of neuroblastoma and small-cell lung cancer cells with an anti-neural cell adhesion molecule immunotoxin.

BACKGROUND: The development of immunotoxins has been hampered by difficulties, particularly in solid tumors, of finding appropriate target antigens and of linking sufficiently potent toxins. PURPOSE: We evaluated the tissue specificity of an immunotoxin, N901-blocked ricin (N901-bR), and assessed its potential for eliminating neural cell adhesion molecule (NCAM)-positive tumor cells in conditions appropriate for in vitro purging, prior to autologous stem cell transplantation, and its potential for myelosuppression. N901-bR consists of a monoclonal antibody (MAb), N901, directed against CD56, an antigen of the family of NCAMs, covalently linked to blocked ricin as the cytotoxic effector moiety. METHODS: The tissue specificity of the N901 MAb and the N901-bR immunotoxin was tested against a wide array of human tumor tissues and normal human tissues by immunohistochemical staining. The cytotoxic activity of N901-bR was tested against both small-cell lung cancer (SCLC) cells and neuroblastoma cells, either alone or among normal bone marrow mononuclear cells, and the efficacy of this treatment to specifically eliminate these cells was evaluated in a limiting dilution assay. In addition, normal bone marrow mononuclear cells were incubated with N901-bR, and the toxic effects of the immunotoxin on normal hematopoietic progenitors was evaluated. RESULTS: N901 and N901-bR exhibited specificity for several neoplasms of neuroectodermal origin, including SCLC and neuroblastoma. Staining of normal tissues was essentially limited to various neuroendocrine cells, cardiac muscle cells, and cells in peripheral nerve tissue. We observed a time- and dose-dependent elimination of tumor cells in vitro, with three logs (i.e., > 99.9%) of malignant cells being killed following only 5 hours of exposure to 10 nM N901-bR. Unconjugated N901 MAb specifically blocked the elimination of NCAM-positive cells by N901-bR, whereas neither an isotype-matched control MAb nor galactose (the ligand of native ricin) had any effect on the activity of the immunotoxin, confirming the specificity of its cytotoxic activity. Importantly, N901-bR used under optimal conditions for in vitro tumor cell depletion was not toxic to hematopoietic precursors. CONCLUSIONS: N901-bR has the properties required to target CD56, an antigen present not only on cells from a large number of cancers of neuroendocrine origin, but also on some important normal tissues. In addition, treatment with this immunotoxin results in the highly effective and specific elimination of neuroblastoma and SCLC cells and does not affect normal hematopoietic progenitors. IMPLICATIONS: N901-bR may have clinical utility for purging of neuroblastoma cells and SCLC cells before autologous stem cell transplantation. Further toxicology studies are warranted to assess the potential of N901-bR for in vivo administration.

Antibodies, Monoclonal↗