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

To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains.
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PMID:N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 776 44

We have investigated the effects of the C-terminal amyloid precursor protein fragment His 657-Lys 676 upon calcium currents in NG108-15 neuroblastoma x glioma hybrid cells. The amyloid precursor protein fragment His 657-Lys 676 (1-10 microM) did not affect calcium currents per se, but clearly blocked the calcium current suppression mediated by both adrenergic alpha 2B- and opioid delta receptors in a concentration-dependent manner. The reverse amyloid precursor protein fragment Lys 676-His 657 and the shorter amyloid precursor protein fragment Gly 659-Lys 676 did not affect calcium current suppression by adrenergic alpha 2B- and opioid delta receptors. The similar interaction of C-terminal amyloid precursor protein with adrenergic alpha 2B- and opioid delta receptors suggest that the effect occurs downstream of the receptor, possibly via the GTP binding protein Go.
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PMID:The amyloid precursor protein fragment His 657-Lys 676 inhibits noradrenaline- and enkephaline-induced suppression of voltage sensitive calcium currents in NG108-15 hybrid cells. 787 Feb 93

The effect of ciliary neurotrophic factor (CNTF) on beta-amyloid precursor protein (APP) gene expression was investigated in cultured rat C6 glioma cells and human SH-SY5Y neuroblastoma cells. CNTF increased APP mRNA abundance in C6 glioma cells in a dose-dependent manner, with an approximately 3-fold increase in maximum observed after 24 h with a concentration of 1 ng/ml. However, no significant differences in the splicing pattern of the three major isoforms of APP mRNA were apparent between control and CNTF-treated C6 glioma cells. CNTF had no effect on APP mRNA abundance in SH-SY5Y neuroblastoma cells. These findings suggest that CNTF can modulate APP mRNA expression and might affect amyloidogenesis in Alzheimer's disease.
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PMID:Ciliary neurotrophic factor induced-increase in beta-amyloid precursor protein mRNA in rat C6 glioma cells. 794 86

Amyloid beta protein (beta/A4 or A beta), the main proteinaceous component of the amyloid depositions of the Alzheimer's brain, derives from the proteolytic processing of the amyloid precursor protein (APP). Cleavage of the amyloid precursor by at least two distinct secretase activities produces soluble secreted APP. The major secretase cleavage (site I) takes place between A beta 16 and 17, while the minor cleavage (site II) takes place after A beta Lys 28 and may produce potentially amyloidogenic secreted APP. Full-length cellular APP is cleaved by secretase intracellularly in the Trans-Golgi Network (TGN) or in post-Golgi vesicles. The resultant soluble APP is transported to the plasma membrane and exocytosed. The biological activity of the APP is still not completely understood, although it seems to act as a cell adhesion molecule. Recent studies have shown that in glioma cells, most of the soluble secreted APP occurs as a chondroitin sulfate proteoglycan (CSPG). In addition, full length APP CSPG has been detected in neuroblastoma and fibroblast cells as well as on the surface of glioma cells, and in human brain. These results suggest that the proteoglycan nature of the APP proteins may be important for their biological function.
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PMID:Cellular processing and proteoglycan nature of amyloid precursor proteins. 823 71

The cellular factors regulating the generation of beta-amyloid from the amyloid precursor protein (APP) are unknown. Activation of protein kinase C (PKC) by phorbol ester treatment inhibited the generation of the 4-kDa beta-amyloid peptide in transfected COS cells, a human glioma cell line, and human cortical astrocytes. An analogue of diacylglycerol, the endogenous cellular activator of PKC, also inhibited the generation of beta-amyloid. Activation of PKC increased the level of secreted APP in transfected COS cells but did not significantly affect the level of secreted APP in primary human astrocytes or in the glioma cell line. Cell-associated APP and the secreted APP derivative, but not beta-amyloid, were phosphorylated on serine residues. Activation of PKC did not increase the level of APP phosphorylation, suggesting that PKC modulates the proteolytic cleavage of APP indirectly by phosphorylation of other substrates. These results indicate that PKC activation inhibits beta-amyloid production by altering APP processing and suggest that beta-amyloid production can be regulated by the phospholipase C-diacylglycerol signal transduction pathway.
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PMID:Inhibition of beta-amyloid production by activation of protein kinase C. 824 86

The beta-amyloid peptide (A beta) is a 4 kDa proteolytic fragment derived from the beta-amyloid precursor protein (beta APP) which is deposited as amyloid fibrils in the brains of patients with Alzheimer's disease. beta APP processing was investigated in C6 glioma cells using several affinity-purified anti-peptide antibodies raised against different domains of the protein. Both direct immunoblot analysis of C6 glioma conditioned medium and metabolic labeling of cells followed by immunoprecipitation of extracellular medium with specific antibodies revealed that these glial cells normally produce and release a soluble 4 kDa peptide which co-migrates with synthetic A beta (1-40) and is specifically recognized by antibodies raised against N- or C-terminal domains of the beta-amyloid peptide. Our results further suggest that glial cells may prove a major source of beta-amyloid production in the nervous tissue.
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PMID:Production of the Alzheimer's beta-amyloid peptide by C6 glioma cells. 826 45

The biological function of the amyloid precursor protein (APP) is still not fully understood. Recently, we reported that secreted truncated APP occurs in a chondroitin sulfate proteoglycan form. Here we present evidence that full length APP-chondroitin sulfate proteoglycan is present on the cell surface of C6 glioma cells. In addition, densitometric quantitation of Western blots showed that approximately 50% of the mature cell-associated full length APP is in the proteoglycan form. These findings suggest that the proteoglycan nature of APP may be important for the implementation of its biological function.
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PMID:Chondroitin sulfate proteoglycan form of cellular and cell-surface Alzheimer amyloid precursor. 836 24

The major component of amyloid plaque cores and cerebrovascular amyloid deposits found in Alzheimer disease is the beta/A4 peptide, which is derived from the Alzheimer amyloid protein precursor (APP). Recent evidence suggests that abnormalities in beta/A4 peptide production or beta/A4 peptide aggregation may underlie cerebral amyloidosis. In the present study, treatment of cells with phorbol dibutyrate, which activates protein kinase C, and/or okadaic acid, which inhibits protein phosphatases 1 and 2A, reduced beta/A4 peptide production by 50-80%. These effects were observed with APP695 and APP751 expressed in stably transfected CHO cells, as well as with endogenous APP in human glioma (Hs 683) cells. Phorbol dibutyrate also decreased beta/A4 peptide production in cells expressing various mutant forms of APP associated with familial Alzheimer disease, one of which was reported to manifest greatly increased beta/A4 peptide production in cultured cells. Mastoparan and mastoparan X, compounds which can activate phospholipase C and hence protein kinase C, also decreased beta/A4 peptide production in CHO cells stably transfected with APP695. A model is presented in which decreases in beta/A4 peptide production can be achieved by accelerating the metabolism of APP through a nonamyloidgenic secretory pathway.
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PMID:Protein phosphorylation inhibits production of Alzheimer amyloid beta/A4 peptide. 841 76

It has previously been shown that stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol (DAG) and activating protein kinase C (PKC), accelerate the breakdown of the amyloid precursor protein (APP) to form soluble, non-amyloidogenic peptides (APPs). This relationship has been demonstrated in human glioma and neuroblastoma cells as well as in transfected human embryonic kidney (HEK) cells and PC12 cells. We now provide evidence that stimulation of metabotropic glutamate receptors (mGluRs), which also are coupled to DAG and PKC, similarly accelerates processing of APP into non-amyloidogenic APPs in hippocampal neurons and cortical astrocytes derived from normal fetal rats. The mGluR antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3), and GF 109203X, an inhibitor of PKC, both blocked the release of APPs from hippocampal neurons and astrocytes evoked by glutamate receptor stimulation. Inasmuch as glutamatergic neurons in cortex and hippocampus are known to be damaged in Alzheimer's disease, our findings suggest that amyloid formation may be enhanced by the resulting glutamate deficiency and that selective mGluR agonists may be useful in facilitating synaptic efficacy and treating the disease.
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PMID:Metabotropic glutamate receptors regulate APP processing in hippocampal neurons and cortical astrocytes derived from fetal rats. 862 10

Amyloid deposition characterizes the pathological lesions of Alzheimer's disease. We investigated the effect of serum deprivation on the regulation of beta-amyloid precursor protein (APP) mRNA expression in C6 glioma cells. Serum deprivation increased APP mRNA levels approximately 4-fold over controls. This increase was accompanied by changes in the pattern of alternative splicing, including the novel alternatively spliced site at exon 15. The proportion of isoforms containing exons 7 and 8 significantly increased from 61% to 68%, while isoforms lacking these exons decreased from 14% to 8%. The proportion of leukocyte-derived APP, which is a novel alternatively spliced isoform lacking exon 15, significantly increased from 19% to 40%. Among the six major isoforms produced by the two independent splicing sites, L-APP752 which contains exons 7 and 8, but lacks exon 15, increased the most (approximately 10-fold). Our findings provide evidence linking APP expression to alterations in alternative splicing at exon 15. These results demonstrate that in glial cells, APP mRNA regulation involves the alteration in alternative splicing at exons 7, 8 and 15, suggesting that not only increased expression but also an imbalance in the relative abundance of the six APP isoforms in stressed condition might affect the amyloidogenesis in Alzheimer's disease.
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PMID:Serum deprivation alters the expression and the splicing at exons 7, 8 and 15 of the beta-amyloid precursor protein in the C6 glioma cell line. 880 9


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