sq-23377 and Astrocytoma

sq-23377 has been researched along with Astrocytoma* in 9 studies

Other Studies

9 other study(ies) available for sq-23377 and Astrocytoma

ArticleYear
Calcineurin regulates nuclear factor I dephosphorylation and activity in malignant glioma cell lines.
    The Journal of biological chemistry, 2013, Aug-16, Volume: 288, Issue:33

    Malignant gliomas (MG), including grades III and IV astrocytomas, are the most common adult brain tumors. These tumors are highly aggressive with a median survival of less than 2 years. Nuclear factor I (NFI) is a family of transcription factors that regulates the expression of glial genes in the developing brain. We have previously shown that regulation of the brain fatty acid-binding protein (B-FABP; FABP7) and glial fibrillary acidic protein (GFAP) genes in MG cells is dependent on the phosphorylation state of NFI, with hypophosphorylation of NFI correlating with GFAP and B-FABP expression. Importantly, NFI phosphorylation is dependent on phosphatase activity that is enriched in GFAP/B-FABP+ve cells. Using chromatin immunoprecipitation, we show that NFI occupies the GFAP and B-FABP promoters in NFI-hypophosphorylated GFAP/B-FABP+ve MG cells. NFI occupancy, NFI-dependent transcriptional activity, and NFI phosphorylation are all modulated by the serine/threonine phosphatase calcineurin. Importantly, a cleaved form of calcineurin, associated with increased phosphatase activity, is specifically expressed in NFI-hypophosphorylated GFAP/B-FABP+ve MG cells. Calcineurin in GFAP/B-FABP+ve MG cells localizes to the nucleus. In contrast, calcineurin is primarily found in the cytoplasm of GFAP/B-FABP-ve cells, suggesting a dual mechanism for calcineurin activation in MG. Finally, our results demonstrate that calcineurin expression is up-regulated in areas of high infiltration/migration in grade IV astrocytoma tumor tissue. Our data suggest a critical role for calcineurin in NFI transcriptional regulation and in the determination of MG infiltrative properties.

    Topics: Adult; Astrocytoma; Calcineurin; Calcium-Binding Proteins; Cell Line, Tumor; Chromatin Immunoprecipitation; Cyclosporine; Glioma; Humans; Immunohistochemistry; Immunoprecipitation; Ionomycin; NFI Transcription Factors; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Protein Transport

2013
HIV-1 infection increases the expression of human endogenous retroviruses type K (HERV-K) in vitro.
    AIDS research and human retroviruses, 2007, Volume: 23, Issue:1

    Antibodies to HERV-K antigens have been linked to HIV-1 infection and expression of HERV-K proteins generates T-cell cytotoxic responses in many cancers. HERV-K RNA and protein abundance was measured in HIV-1-infected and control cells. In vitro exposure of HIV-1 laboratory-adapted and primary isolates on U87MG cells increased the expression of HERV-K RNA in a dose-dependent manner. HERV-K RNA and protein burdens were significantly increased in HIV-1-producing H9 cell lines compared to H9 cells. The expression of HERV-K was synergistically increased in HIV-1-infected PBMCs after stimulation with PMA/ionomycin. Furthermore, the expression of HERV-K in PBMCs, and particularly in CD4(+) T cells, was higher in HIV-1 patients compared to control subjects. The expression of HERV-K might be related to HIV-1 pathogenesis and AIDS-associated cancers.

    Topics: Astrocytoma; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Endogenous Retroviruses; Flow Cytometry; Gene Expression; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV-1; Humans; In Vitro Techniques; Ionomycin; Ionophores; Leukocytes, Mononuclear; RNA, Viral; Tetradecanoylphorbol Acetate; Viral Load

2007
Muscarinic-receptor-mediated inhibition of insulin-like growth factor-1 receptor-stimulated phosphoinositide 3-kinase signalling in 1321N1 astrocytoma cells.
    The Biochemical journal, 2004, May-01, Volume: 379, Issue:Pt 3

    In 1321N1 astrocytoma cells, stimulation of the IGF-1 (insulin-like growth factor-1) receptor increased the association of PI3K [phosphoinositide (PI) 3-kinase] activity with IRS-1 (insulin re-ceptor substrate 1), and increased the cellular concentration of PtdIns(3,4,5)P3. Carbachol, acting on M3 muscarinic receptors, inhibited insulin-, but not PDGF (platelet-derived growth factor)-, stimulated responses by approximately 50%. The inhibition of IRS-1-associated PI3K activity by carbachol (i) was rapid (<1 min), persistent (> or =60 min) and potent (half-maximal concentration approximately 1 microM); (ii) was reproduced by stimuli for several phospholipase-C-coupled receptors; (iii) was prevented by the inhibition of protein kinase C, but not by chelation of intracellular Ca2+; and (iv) was not blocked or reproduced by inhibitors or stimuli respectively of mitogen-activated protein kinase, PI3K, protein kinase B or the mammalian target of rapamycin. However, the effects of carbachol were prevented by sodium vanadate, a protein tyrosine phosphatase inhibitor, and were accompanied by reduced insulin-stimulated IRS-1 tyrosine phosphorylation and recruitment of the 85 kDa regulatory subunit of PI3K to IRS-1, but not by reduced IGF-1 receptor kinase activity. The inhibitory effect of carbachol was reproduced by okadaic acid, a protein serine/threonine phosphatase inhibitor, but not by PDGF, yet all three agents stimulated the serine phosphorylation of IRS-1 at residues Ser312, Ser616 and Ser636/639, albeit to different extents. Thus muscarinic receptors may inhibit insulin signalling by promoting IRS-1 tyrosine dephosphorylation and/or by uncoupling IRS-1 from the stimulated IGF-1 receptor by stimulating IRS-1 serine phosphorylation. However, the proportion of IRS-1 molecules phosphorylated at a particular site or the phosphorylation of additional IRS-1 serine residues other than those noted above must be important.

    Topics: Astrocytoma; Calcium; Carbachol; Cell Line, Tumor; Enzyme Activation; Humans; Inositol 1,4,5-Trisphosphate; Insulin; Insulin Receptor Substrate Proteins; Ionomycin; Mitogen-Activated Protein Kinases; Okadaic Acid; Phosphatidylinositol 3-Kinases; Phosphoproteins; Phosphorylation; Phosphoserine; Phosphotyrosine; Platelet-Derived Growth Factor; Protein Kinase C; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptor, IGF Type 1; Receptors, Muscarinic; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Tetradecanoylphorbol Acetate; Type C Phospholipases

2004
Sustained entry of Ca2+ is required to activate Ca2+-calmodulin-dependent phosphodiesterase 1A.
    The Journal of biological chemistry, 2004, Sep-24, Volume: 279, Issue:39

    Regulation of adenylyl cyclases (ACs) by Ca2+ requires capacitative Ca2+ entry (CCE) (Cooper, D. M. F. (2003) Biochem. J. 375, 517-529), but whether Ca2+-sensitive phosphodiesterases (PDEs) are similarly discriminating has never been addressed. In the present study, a variety of conditions were devised to manipulate [Ca2+]i so that we could ask whether PDE1 selectively responds to different modes of elevating [Ca2+]i, viz. Ca2+ released from intracellular stores and various modes of Ca2+ entry. In 1321N1 human astrocytoma cells, the endogenous PDE1 (identified as PDE1A by reverse transcriptase-PCR) was largely insensitive to Ca2+ released from carbachol-sensitive stores but was robustly stimulated by a similar rise in [Ca2+]i due to carbachol-induced Ca2+ influx. Gd3+, which effectively blocked thapsigargin-induced CCE and its effect on PDE1A, also inhibited the activation of PDE1A by carbachol-induced Ca2+ entry. However, non-selective ionomycin-mediated Ca2+ entry also activated PDE1A, so that, unlike Ca2+-sensitive ACs, PDE1A cannot discriminate between the different sources of Ca2+ entry. Fractionation of the cells revealed that the Ca2+-calmodulin-stimulated PDE activity was not present at the plasma membrane but was associated with the cytosol and the organellar compartments of the cell. Therefore, the apparent disparity between PDE1A and ACs is likely to be the consequence of their differential subcellular localization. Nevertheless, in a physiological context, where artificial modes of elevating [Ca2+]i are not available, as with ACs, a dependence on CCE would be evident, and it would be the duration of this influx of Ca2+ that would determine how long PDE1A was activated.

    Topics: Adenylyl Cyclases; Astrocytoma; Calcium; Carbachol; Cell Cycle; Cell Line, Tumor; Cell Membrane; Cholinergic Agonists; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 1; Cytosol; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gadolinium; Humans; Ionomycin; Isoproterenol; Nucleotides, Cyclic; Phosphoric Diester Hydrolases; Reverse Transcriptase Polymerase Chain Reaction; Subcellular Fractions; Thapsigargin; Time Factors

2004
Peroxynitrite modulates tyrosine phosphorylation and phosphoinositide signalling in human neuroblastoma SH-SY5Y cells: attenuated effects in human 1321N1 astrocytoma cells.
    The Biochemical journal, 1998, Apr-15, Volume: 331 ( Pt 2)

    Peroxynitrite may contribute to oxidative stress involving neurodegeneration in several disorders, including Alzheimer's disease. As with other reactive oxygen species, peroxynitrite might affect neuronal signalling systems, actions that could contribute to adaptive or deleterious cellular outcomes, but such effects have not previously been studied. To address this issue directly, peroxynitrite (50-500 microM) was administered to human neuroblastoma SH-SY5Y cells to assess its effects on protein tyrosine nitration, phosphoinositide signalling and protein tyrosine phosphorylation. Peroxynitrite rapidly increased the nitrotyrosine immunoreactivity of numerous proteins, primarily in the cytosol. Peroxynitrite inhibited, in a concentration-dependent manner, phosphoinositide hydrolysis stimulated by activation of muscarinic receptors with carbachol and the inhibition was greater after the depletion of cellular glutathione. In comparison, muscarinic receptor-stimulated phosphoinositide hydrolysis in human astrocytoma 1321N1 cells was less vulnerable to inhibition by peroxynitrite either without or with prior depletion of glutathione. There was a large, rapid and reversible increase in the tyrosine phosphorylation of the p120 Src substrate in peroxynitrite-treated SH-SY5Y cells, a response that was potentiated by glutathione depletion; in contrast, peroxynitrite decreased the tyrosine phosphorylation of focal adhesion kinase and paxillin. Tyrosine phosphorylation of p120 in 1321N1 astrocytoma cells was less sensitive to modulation by peroxynitrite. Thus alterations in phosphoinositide signalling and protein tyrosine phosphorylation were greater in neuroblastoma than astrocytoma cells, and modulation of these signalling processes probably contributes to neuronal mechanisms of the response to peroxynitrite.

    Topics: Astrocytoma; Cell Membrane; Cytosol; Humans; Hydrolysis; Ionomycin; Neuroblastoma; Nitrates; Phosphatidylinositols; Phosphoproteins; Phosphorylation; Phosphotyrosine; Signal Transduction; Sodium Fluoride; Tumor Cells, Cultured

1998
Identification of a B2-bradykinin receptor linked to phospholipase C and inhibition of dopamine stimulated cyclic AMP accumulation in the human astrocytoma cell line D384.
    Naunyn-Schmiedeberg's archives of pharmacology, 1992, Volume: 346, Issue:3

    We have examined the activation of a phospholipase C signal transduction pathway by a B2-bradykinin receptor in the human astrocytoma cell line D384 and how this influences D1-dopamine receptor stimulated cyclic AMP accumulation. Addition of bradykinin to D384 cells resulted in a concentration-dependent (10(-11)-10(-6) M) increase in the accumulation of [3H]inositol phosphates and a similar concentration-dependent transient increase in specific [3H]beta-phorbol-12,13-dibutyrate binding which is indicative of translocation of protein kinase C from the cytosol to the membrane. Changes in intracellular Ca2+ of single cells, measured using the fluorescent indicator dye fura-2, indicated that bradykinin produced a rapid, but transient, increase in intracellular calcium. The Ca2+ response was largely independent of extracellular Ca2+ supporting the idea that receptor activation leads to mobilization of Ca2+ from intracellular stores. However, extracellular Ca2+ was required for a response to a rechallenge with bradykinin. The bradykinin B2-receptor agonist kallidin increased cytosolic Ca2+ in a similar manner to bradykinin. The Ca2+ response to bradykinin could be partially reduced in the presence of the B2-receptor antagonist [D-Arg0-Hyp,D-Phe7,beta-(2-Thienyl)-Ala5,8]-bradykinin, whereas the B1-receptor agonists (Des-Arg9]-bradykinin and [Des-Arg10]-kallidin were ineffective. Bradykinin was also found to attenuate dopamine stimulated cyclic AMP accumulation in D384 cells, at similar concentrations previously observed to stimulate the phospholipase C signal transduction pathway, in the presence of the phosphodiesterase inhibitor, rolipram. In contrast, no attenuation was observed in the presence of the phosphodiesterase inhibitor 1-isobutyl 3-methylxanthine, although the level of dopamine stimulated cyclic AMP observed was lower than in the presence of rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Astrocytoma; Bradykinin; Calcium; Cyclic AMP; Dopamine; Humans; Inositol Phosphates; Ionomycin; Phorbol Esters; Receptors, Bradykinin; Receptors, Dopamine D1; Receptors, Neurotransmitter; Tumor Cells, Cultured; Type C Phospholipases

1992
Histamine stimulates glycogenolysis in human astrocytoma cells by increasing intracellular free calcium.
    Brain research, 1992, Oct-02, Volume: 592, Issue:1-2

    Astrocytes from a variety of sources, including the human UC-11MG astrocytoma line, express receptors for histamine on their plasma membranes, but the function of these receptors is largely unknown. Here we report studies on the effect of histamine on newly synthesized glycogen in the human astrocytoma-derived cell line, UC-11MG. We have found [3H]glycogen hydrolysis with a EC50 of 2 microM and a maximum effect of 30% at 300 microM histamine. The glycogenolytic effect of histamine was completely blocked by the H1 receptor antagonist, mepyramine, and was insensitive to the H2 receptor antagonist, cimetidine. Histamine-induced glycogenolysis was significantly reduced in the absence of extracellular Ca2+ and the residual response could be accounted for by Ca2+ released from intracellular stores. The Ca2+ ionophore, ionomycin, induced a similar concentration-dependent increase in both intracellular Ca2+ concentration and in glycogenolysis. These results suggest that one function of astrocytic histamine receptors in vivo may be the stimulation of glucose release from astrocytes, and that this process is mediated by increased intracellular free Ca2+. The glycogenolytic effect of histamine and other neurotransmitters in different systems, and the possible implication of astrocytic glycogenolysis in the pathophysiology of ischemia are discussed.

    Topics: Astrocytoma; Calcium; Dose-Response Relationship, Drug; Egtazic Acid; Glucose; Glycogen; Histamine; Histamine Antagonists; Humans; Intracellular Membranes; Ionomycin; Receptors, Histamine; Tumor Cells, Cultured

1992
Multiple pathways for signal transduction through the muscarinic cholinergic receptor.
    Progress in brain research, 1990, Volume: 84

    Topics: Animals; Astrocytoma; Calcium; Carbachol; Cell Division; Cell Line; Choline; Ionomycin; Kinetics; Phospholipase D; Protein Kinase C; Receptors, Muscarinic; Signal Transduction; Tetradecanoylphorbol Acetate; Type C Phospholipases

1990
Increases in intracellular Ca2+ regulate the binding of [3H]phorbol 12,13-dibutyrate to intact 1321N1 astrocytoma cells.
    The Journal of biological chemistry, 1989, Feb-25, Volume: 264, Issue:6

    The redistribution of protein kinase C (Ca2+/phospholipid-dependent protein kinase) from a cytosolic or a loosely associated membrane compartment to a more integral membrane compartment is stimulated by Ca2+ in vitro. This event is thought to be necessary for activation of the enzyme. To determine whether such a redistribution of protein kinase C occurs following hormonally stimulated increases in cytoplasmic Ca2+, we measured [3H]phorbol 12,13-dibutyrate ([3H]PDB) binding to protein kinase C in intact 1321N1 astrocytoma cells. The muscarinic agonist carbachol causes a 2-fold increase in [3H]PDB binding. This increase is transient, peaking at 1 min and returning toward control levels by 5 min. Scatchard analysis of [3H]PDB binding in the presence of carbachol reveals a 2-fold increase in the Bmax and no change in the KD compared to control values. This increase in Bmax likely represents a redistribution of protein kinase C to the membrane because [3H]PDB binding in intact cells is predominantly to membrane-associated enzyme. The Ca2+ ionophore ionomycin, and two other Ca2+-mobilizing hormones, bradykinin and histamine, mimic the effects of carbachol. Furthermore, when hormone-sensitive Ca2+ stores are depleted by prior agonist treatment, the carbachol-induced increases in intracellular [Ca2+] and [3H]PDB binding are completely blocked. Under these conditions, phosphoinositide hydrolysis and diacylglycerol (DAG) formation are not inhibited. We also examined the time course of DAG accumulation in response to carbachol. DAG is not yet significantly elevated when the increase in [3H]PDB binding is maximal. Furthermore, [3H]PDB binding has returned to control levels when DAG concentrations are maximally elevated. These data suggest that hormone-stimulated increases in cytoplasmic Ca2+ cause a marked and rapid redistribution of protein kinase C which precedes any significant increase in DAG. Our findings also demonstrate that [3H]PDB binding to intact cells may be a useful measure of the ability of Ca2+-mobilizing hormones to affect protein kinase C.

    Topics: Astrocytoma; Binding Sites; Bradykinin; Calcium; Carbachol; Cell Membrane; Cytosol; Diglycerides; Ethers; Histamine; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Ionomycin; Kinetics; Phorbol 12,13-Dibutyrate; Protein Kinase C; Receptors, Muscarinic; Tumor Cells, Cultured

1989