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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) we have investigated the expression of the neurotrophin receptors p75NGFR, trkA, and trkB mRNAs in cultures of rat pup type I astrocytes and in the C6 rat glioma cell line. All three neurotrophin receptor mRNAs are expressed in both C6 cells and in type I astrocytic cultures. p75NGFR mRNA levels are increased by either cycloheximide or nerve growth factor (NGF) treatment of C6 cells as measured using RT-PCR. Type I astrocyte cultures also expressed p75NGFR mRNA and NGF treatment increased p75NGFR mRNA levels in these cultures. TrkB mRNA levels were increased by cycloheximide treatment of type I astrocyte cultures but not by NGF treatment. Using RT-PCR, trkA mRNA was detected in astrocytic cultures as well as in the rat C6 and PC-12 cell lines. We conclude that cultures of type I astrocytes express active NGF receptors and that glia can elicit a response to NGF as seen by an increase in p75NGFR mRNA levels following exposure to NGF.
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PMID:Expression of p75NGFR TrkA, and TrkB mRNA in rat C6 glioma and type I astrocyte cultures. 127 89

The neurotrophic proteins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are related in their primary amino acid structures. In this study we investigated the extent to which the low-affinity NGF receptor (LNGFR) in C6 glioma cells can discriminate between the neurotrophins NGF and BDNF. LNGFR-immunoreactivity (IR) was studied in C6 cells treated for 16 hr with NGF (50 ng/ml) or BDNF (10 ng/ml), using immunogold labelling and electron microscopic morphometric analysis. The cells were exposed to the anti-NGFR antibody 192-IgG, followed by immunoglobulin conjugated with colloidal gold. Untreated C6 cells exhibited some surface gold label (positive LNGFR-IR). Cells treated with NGF or BDNF displayed significantly increased LNGFR-IR on all surfaces in terms of gold labeling, which was more pronounced in NGF-treated cells. LNGFR-IR was also localized in coated endocytotic vesicles, in smooth endoplasmic reticulum, and in secondary multivesicular lysosomes in neurotrophin-treated and untreated cells. The increase in LNGFR protein was further substantiated by a correspondingly higher content of LNGFR mRNA detected after 15 hr of either NGF or BDNF treatment. These results suggest that the LNGFR in glial cells can be upregulated by the structurally related neurotrophins NGF and BDNF.
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PMID:Nerve growth factor (NGF) receptors in a central nervous system glial cell line: upregulation by NGF and brain-derived neurotrophic factor. 145 86

Prompted by the recent discovery that neurotrophins, which are known to be biologically active as noncovalently linked homodimers, can also be induced to form biologically active heterodimers in vitro, we have investigated the biosynthesis of neurotrophin heterodimers by transfected mammalian cells. When COS cells were cotransfected with expression plasmids for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), or neurotrophin-3 (NT-3), the appropriate heterodimers were detected in the conditioned medium by immunoprecipitation and, in the case of NGF.NT-3, using a two-site enzyme-linked immunosorbent assay. Heterodimer formation occurred predominantly intracellularly and did not require precursor cleavage, because heterodimers containing pro-NGF and pro-BDNF were detected in the conditioned medium. When rat C6 glioma cells or mouse AtT-20 neuroendocrine cells were cotransfected with expression plasmids for NGF and NT-3, NGF.NT-3 heterodimer was detected at levels comparable with those of homodimeric NGF and NT-3, indicating that heterodimer formation can occur at significant levels in a variety of cell types. These data provide evidence that NGF, BDNF, and NT-3 are capable of forming heterodimers when coexpressed in mammalian cells and suggest that such heterodimers are likely to be formed in vivo when a single cell expresses multiple neurotrophins.
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PMID:The biosynthesis of neurotrophin heterodimers by transfected mammalian cells. 774 82

Ciliary neurotrophic factor (CNTF) has been shown to modulate the in vitro and in vivo survival, proliferation and differentiation of many neuronal cell types. Evidence indicates that it produces most if not all these effects by binding to a receptor subunit referred to as the CNTF receptor alpha component (CNTFR alpha). We cloned a cDNA encoding part of the rat CNTFR alpha and used it in Northern analyses to study CNTFR alpha mRNA expression. Examination of various tissues of embryonic day 18 and postnatal day 14 rats indicated that CNTFR alpha mRNA is primarily but not exclusively expressed in brain at these stages of development. Further studies revealed that the CNTFR alpha transcripts are present throughout brain development from embryonic day 12 to adulthood and display a widespread distribution in the adult brain. A survey of rodent cell lines detected highest CNTFR alpha mRNA concentrations in neuronal lines and a low concentration in a Schwann cell derived line. CNTFR alpha mRNA was not detected in fibroblast lines and a glioma line. Finally, nerve growth factor treatment decreased CNTFR alpha mRNA levels in PC12 cells. This result demonstrates that signal transduction processes activated by a neurotrophin can influence CNTF activated signal transduction processes. Such cross-talk may play an important in vivo role in the development and maintenance of the many neuronal cell types that are responsive to both neurotrophins and CNTF.
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PMID:CNTF receptor alpha mRNA expression in rodent cell lines and developing rat. 780 24

The role of the low-affinity neurotrophin receptor (p75NTR) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75NTR in T9 cells and NIH 3T3 cells overexpressing p75NTR. Expression of an epidermal growth factor receptor-p75NTR chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75NTR is capable of signaling independently of the trk neurotrophin receptor (p140trk) and that ceramide may be a mediator in neurotrophin biology.
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PMID:Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. 807 74

The expression of neurotrophin (NGF, BDNF, and NT-3) mRNAs in 24 cell lines derived from human malignant gliomas was studied by Northern analysis. Widespread expression of neurotrophin genes was found with BDNF being the most abundantly expressed. Nearly all cell lines expressed BDNF, and about two-thirds of the cell lines expressed NGF and NT-3. Half of the cell lines analyzed expressed all three neurotrophins. Secretion of NGF into the medium of several cell lines could be detected by ELISA and a PC12 neurite outgrowth assay. Immuno- and bioactive NGF was isolated from conditioned medium of one cell line. No evidence of expression of the neurotrophin receptors trk and trkB by Northern analysis was found. Receptor crosslinking with radiolabeled cognate ligands failed to detect functional receptors in all but one cell line. In this cell line a receptor complex for BDNF was found that corresponded to truncated trkB receptors that lack the signal transducing tyrosine kinase domain. Neurotrophins did not stimulate mitosis of the glioma cultures. The findings suggest that production of neurotrophins by glioma cells is a general phenomenon, although neurotrophins made by gliomas lacking their receptors may not play an autocrine but rather a paracrine role.
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PMID:Neurotrophin gene expression by cell lines derived from human gliomas. 845 May 61

The low-affinity nerve growth factor (NGF) receptor (LNGFR) binds the neurotrophins NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) with similar affinities. Here we report on the ability of NT-3 to regulate the expression of the LNGFR in C6 glioma cells. LNGFR-like immunoreactivity (LNGFR-IR) was examined in C6 cells treated for 16 h with NT-3 and exposed to the antibody 192-IgG followed by immunoglobulins conjugated with colloidal gold by means of ultrastructural morphometric analysis. Untreated C6 cells exhibited some positive LNGFR-IR, while C6 cells treated with NT-3 displayed significantly increased (2.3 fold) LNGFR-IR. The increase in LNGFR protein was accompanied by a greater quantity of LNGFR mRNA in NT-3-treated cells. Thus, LNGFR can be upregulated by the structurally related neurotrophin NT-3.
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PMID:Neurotrophin-3 upregulates NGF receptors in a central nervous system glial cell line. 845 34

The role of the NT-3 has been implicated in the survival of progenitor oligodendrocytes in culture. The object of this study was to investigate the expression of the TrkC receptor and its responsiveness in glial cells. We report the expression of two TrkC receptor isoforms in rat primary oligodendrocyte cultures, a glial progenitor cell line, CG-4, and in C6 glioma cells. The reverse transcription-polymerase chain reaction-aided amplification of glial trkC with specific primers from the kinase domain, followed by its cloning and sequencing, shows the presence of two trkC transcripts. The sequence of one of the transcripts is homologous to a previously identified trkC isoform which encodes a functional receptor. The other transcript contains a 42-bp insert in the kinase domain. A Western blot of CG-4 and C6 probed with antibody to a TrkC revealed the presence of gp145-kDa protein band. The investigations revealed a rapid autophosphorylation of gp145TrkC in CG-4 and C6 cells in the presence of its specific ligand, NT-3. Furthermore, K252a, a neurotrophin-specific inhibitor, abolishes the NT-3-mediated receptor autophosphorylation. We also examined other NT-3-dependent phosphorylation of cellular substrates in oligodendroglial cells. Interestingly, we observed phosphorylation of phospholipase C gamma-1 in CG-4 and C6 cells, and phosphorylation of phosphatidylinositol 3-kinase in C6 cells in the presence of NT-3. Both the NT-mediated phosphorylation of phospholipase C gamma-1 and phosphorylation of phosphatidylinositol 3-kinase are blocked in the presence of K252a. The detection of the NT-3-mediated early signal transduction events demonstrates that TrkC receptor exhibits NT-3-mediated intracellular response in oligodendroglial cells.
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PMID:Neurotrophin activates signal transduction in oligodendroglial cells: expression of functional TrkC receptor isoforms. 877 70

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is known to regulate the expression of neurotrophins [45,46]. Here, we report that 1,25-(OH)2D3 does not influence the expression of truncated or full-length forms of trkB and trkC receptors mRNAs in primary cultures of astrocytes and in C6 glioma cells. In contrast, low concentrations of 1,25-(OH)2D3 increased low-affinity neurotrophin receptor (P75NTR) mRNA and protein levels in C6 glioma cells. Putative vitamin D responsive elements (VDRE) in the P75NTR promoter have been investigated by transfecting plasmids containing sequences from P75NTR promoter fused to a cat reporter gene. A region between -610 and -860 bp upstream from the translation start codon was found to respond to 1,25-(OH)2D3. Interestingly, 1,25-(OH)2D3 does not regulate P75NTR in primary cultures of astrocytes even at concentration as high as 10(-7) M. Since long-term treatment of 1,25-(OH)2D3 induces cell death in C6 glioma cells but not in primary astrocytes [41], the possible involvement of P75NTR in 1,25-(OH)2D3-induced cell death is discussed. Finally, in-vivo studies show that treatment of 15-day-old and adult rats with 1,25-(OH)2D3 leads to a decrease in the level of P75NTR mRNA in the spinal cord but does not influence its expression in dorsal root ganglion or sciatic nerve. These results suggest that 1,25-(OH)2D3 may have a role in the specific regulation of P75NTR in vivo.
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PMID:1,25-Dihydroxyvitamin D3 regulates the expression of the low-affinity neurotrophin receptor. 888 59

Growth factors are known to regulate glioma proliferation. The glioma cell lines U87 and T98G were examined for evidence of an autocrine stimulatory loop involving the neurotrophin family of growth factors. Although neurotrophin-3 and TrkC RNA were detected by reverse transcription-PCR, there was no evidence of significant interaction between neurotrophin-3 and its cognate receptor TrkC. The microbial alkaloid K252a has been described to inhibit both Trk tyrosine kinase activity and neuroblastoma cell proliferation. K252a inhibited proliferation in U87 (IC50 = 1170 nM) and T98G (IC50 = 529 nM) but induced apoptosis in U87 cells only. At concentrations of 500 nM to 1 microM, K252a blocked only platelet-derived growth factor (PDGF)-mediated receptor autophosphorylation. These results suggest that an autocrine loop involving PDGF is functional and important for maintaining tumor growth. There is no evidence to support the existence of a neurotrophin-mediated autocrine loop. K252a, through inhibition of PDGF signal transduction, may be a novel therapeutic agent in the treatment of human gliomas.
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PMID:K252a inhibits proliferation of glioma cells by blocking platelet-derived growth factor signal transduction. 981 48


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