herbimycin and Glioma

herbimycin has been researched along with Glioma* in 7 studies

Other Studies

7 other study(ies) available for herbimycin and Glioma

ArticleYear
Protein tyrosine kinase-dependent regulation of adenylate cyclase and phosphatidylinositol 3-kinase activates the expression of glial fibrillary acidic protein upon induction of differentiation in rat c6 glioma.
    Cell biology international, 2001, Volume: 25, Issue:5

    Glial fibrillary acidic protein (GFAP) is expressed upon cAMP-mediated induction of differentiation of glial progenitor cells into type II astrocytes. The protein is regulated by hormones, growth factors and cytokines but the signal transduction pathways involved in the regulation of GFAP expression are largely unknown. Specific protein kinase inhibitors were used to study their effect on the expression of GFAP in rat C6 glioma cells. Herbimycin A, a selective protein tyrosine kinase inhibitor, reduced GFAP mRNA and protein expression upon cAMP analog or beta-adrenergic receptor-mediated induction of differentiation. The latter inhibitor attenuated the elevation of cAMP by adenylate cyclase and abolished the activity of phosphatidylinositol 3-kinase (PI 3-K). These data indicate that GFAP expression is regulated by protein tyrosine phosphorylations, modulating the cAMP concentration and PI 3-K activity in C6 glioma cells.

    Topics: Adenylyl Cyclases; Adrenergic beta-Agonists; Androstadienes; Animals; Anti-Bacterial Agents; Benzoquinones; Cell Differentiation; Chromones; Cyclic AMP; Enzyme Inhibitors; Flavonoids; Gene Expression; Glial Fibrillary Acidic Protein; Glioma; Indoles; Isoproterenol; Isoquinolines; Lactams, Macrocyclic; Maleimides; Morpholines; Phosphatidylinositol 3-Kinases; Protein-Tyrosine Kinases; Quinones; Rats; Rifabutin; Sirolimus; Sulfonamides; Tumor Cells, Cultured; Wortmannin

2001
Inhibition of I kappaB-alpha phosphorylation at serine and tyrosine acts independently on sensitization to DNA damaging agents in human glioma cells.
    British journal of cancer, 2000, Volume: 82, Issue:1

    Molecular mechanisms and/or intrinsic factors controlling cellular radiosensitivity are not fully understood in mammalian cells. The recent studies have suggested that nuclear factor kappaB (NF-kappaB) is one of such factors. The activation and regulation of NF-kappaB are tightly controlled by IkappaB-alpha, a cellular inhibitory protein of NF-kappaB. Most importantly, phosphorylation regulates activity of the inhibitor IkappaB-alpha, which sequesters NF-kappaB in the cytosol. Two different pathways for the phosphorylation of IkappaB-alpha are demonstrated, such as serine (at residues 32 and 36) and tyrosine (at residue 42) phosphorylations. To assess a role of the transcription factor, NF-kappaB, on cellular sensitivity to DNA damaging agents, we constructed three different types of expression plasmids, i.e. S-IkappaB (mutations at residues 32 and 36), Y-IkappaB (mutation at residue 42) and SY-IkappaB (mutations at residues 32, 36 and 42). The cell clones expressing S-IkappaB and Y-IkappaB proteins became sensitive to X-rays as compared with the parental and vector-transfected cells. The cell clones expressing SY-IkappaB were further radiosensitive. By the treatment with herbimycin A, an inhibitor of phosphorylation, the X-ray sensitivity of cells expressing SY-IkappaB did not change, while that of the cells expressing S-IkappaB and Y-IkappaB and the parental cells was enhanced. Change in the sensitivity to adriamycin and UV in those clones was very similar to that in the X-ray sensitivity. The inhibition of IkappaB-alpha phosphorylation at serine and tyrosine acts independently on the sensitization to X-rays, adriamycin and UV. These findings suggest that the transcriptional activation induced by NF-kappaB may play a role in the DNA damage repair. The present study proposes a possibility that the inactivation of NF-kappaB by inhibition of both serine and tyrosine phosphorylations may be useful for the treatment of cancer in radio- and chemotherapies.

    Topics: Antineoplastic Agents; Benzoquinones; Cell Cycle; DNA Damage; DNA, Neoplasm; Dose-Response Relationship, Radiation; Doxorubicin; Enzyme Activation; Enzyme Inhibitors; Genetic Vectors; Glioma; Humans; I-kappa B Kinase; Lactams, Macrocyclic; Ligases; NF-kappa B; Phosphorylation; Protein Serine-Threonine Kinases; Quinones; Radiation Tolerance; Rifabutin; Sequence Deletion; Serine; Time Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Tyrosine; Ultraviolet Rays

2000
Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB lin
    The Journal of biological chemistry, 1999, May-28, Volume: 274, Issue:22

    We previously reported that several stresses can induce cytokine-induced neutrophil chemoattractant expression in a nuclear factor kappaB (NF-kappaB)-dependent manner. In this study, we focused further on the regulation of NF-kappaB. The activation of NF-kappaB and the subsequent cytokine-induced neutrophil chemoattractant induction in response to interleukin-1beta (IL-1beta) were inhibited by proteasome inhibitors, MG132 and proteasome inhibitor I. Translocation of NF-kappaB into nuclei occurs by the phosphorylation, multi-ubiquitination, and degradation of IkappaBalpha, a regulatory protein of NF-kappaB. Nascent IkappaBalpha began to degrade 5 min after treatment with IL-1beta and disappeared completely after 15 min. However, IkappaBalpha returned to basal levels after 45-60 min. Interestingly, resynthesized IkappaBalpha was already phosphorylated at Ser-32. These results suggest that 1) the upstream signals are still activated, although the translocation of NF-kappaB peaks at 15 min; and 2) the regulated protein(s) acts downstream of IkappaBalpha phosphorylation. Western blotting showed that the resynthesized and phosphorylated IkappaB molecules were also upward-shifted by multi-ubiquitination in response to IL-1beta treatment. On the other hand, ATP-dependent Leu-Leu-Val-Tyr cleaving activity transiently increased, peaked at 15 min, and then decreased to basal levels at 60 min. Furthermore, the cytosolic fraction that was stimulated by IL-1beta for 15 min, but not for 0 and 60 min, could degrade phosphorylated and multi-ubiquitinated IkappaBalpha. These results indicate that the transient translocation of NF-kappaB in response to IL-1beta may be partly dependent on transient proteasome activation.

    Topics: Animals; Benzoquinones; Chemokines, CXC; Chemotactic Factors; Cysteine Endopeptidases; DNA-Binding Proteins; Enzyme Activation; Gene Expression Regulation; Glioma; Growth Substances; I-kappa B Proteins; Intercellular Signaling Peptides and Proteins; Interleukin-1; Lactams, Macrocyclic; Leupeptins; Multienzyme Complexes; NF-kappa B; NF-KappaB Inhibitor alpha; Oligopeptides; Phosphorylation; Protease Inhibitors; Proteasome Endopeptidase Complex; Quinones; Rats; Rifabutin; RNA, Messenger; Transcriptional Activation; Tumor Cells, Cultured; Ubiquitins

1999
Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP.
    International journal of cancer, 1999, Jul-19, Volume: 82, Issue:2

    Hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells. Treatment of U251 human glioblastoma cells with HGF/SF resulted in enhanced secretion of MMP-2 with an increased level of the active form. This was accompanied by enhanced expression (2.5-fold) of mRNA specific for MMP-2. The stimulatory effect of HGF/SF on MMP-2 expression did not occur in the presence of herbimycin A, a protein tyrosine kinase inhibitor. MT1 -MMP, a cell-surface activator of proMMP-2, was also up-regulated by HGF/SF in a dose-dependent manner. By contrast, the level of TIMP- 1 mRNAs was not altered significantly and that of TIMP-2 was reduced mildly by the HGF/SF treatment, suggesting that HGF/SF may eventually modulate a balance between MMP-2 and TIMPs in favor of the proteinase activity in the glioma cell microenvironment. HGF/SF also stimulated MMP-2 expression of other glioblastoma cell lines. Since glioblastomas frequently co-express HGF/SF and its receptor, our results suggest that HGF/SF might contribute to the invasiveness of glioblastoma cells through autocrine induction of MMP-2 expression and activation.

    Topics: Benzoquinones; Brain Neoplasms; Disease Progression; Enzyme Induction; Enzyme Inhibitors; Epidermal Growth Factor; Gelatinases; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Hepatocyte Growth Factor; Humans; Lactams, Macrocyclic; Matrix Metalloproteinase 2; Matrix Metalloproteinases, Membrane-Associated; Metalloendopeptidases; Neoplasm Invasiveness; Neoplasm Proteins; Protein-Tyrosine Kinases; Quinones; Recombinant Proteins; Rifabutin; RNA, Messenger; RNA, Neoplasm; Signal Transduction; Stimulation, Chemical; Tumor Cells, Cultured

1999
Tyrosine kinase inhibitors suppress N-type and T-type Ca2+ channel currents in NG108-15 cells.
    Pflugers Archiv : European journal of physiology, 1998, Volume: 436, Issue:1

    Modulation of Ca2+ channel activity by protein kinases constitutes one of the major mechanisms regulating neuronal functions. Here, we explored the possible modulation of neuronal Ca2+ channels by protein tyrosine kinases (PTKs). To this end, the effects of PTK inhibitors on whole-cell Ba2+ currents (IBa) through voltage-gated Ca2+ channels were analysed in differentiated NG108-15 neuroblastoma x glioma hybrid cells. Genistein suppressed IBa in a concentration-dependent fashion (IC50 = 22 microM). Although daidzein, an analogue of genistein that is devoid of PTK inhibitory activity, also suppressed IBa, we estimated that specific PTK inhibition by genistein reduced IBa amplitude by 30%. In addition, lavendustin A (20 microM) and herbimycin A (20 microM), two other distinct PTK inhibitors, depressed IBa by 22% and 20%, respectively. Genistein suppressed N-type and T-type currents, sparing L-type current, and its effect was independent of G protein activation. The results suggest that the activity of neuronal Ca2+ channels can be modulated by PTKs, opening the possibility that some of the functions of PTKs in the nervous system are mediated by Ca2+ channel modulation.

    Topics: Animals; Benzoquinones; Calcium Channel Blockers; Calcium Channels; Electric Conductivity; Enzyme Inhibitors; Genistein; Glioma; GTP-Binding Proteins; Hybrid Cells; Isoflavones; Kinetics; Lactams, Macrocyclic; Neuroblastoma; Nifedipine; omega-Conotoxin GVIA; Peptides; Phenols; Protein-Tyrosine Kinases; Quinones; Rats; Rifabutin; Tumor Cells, Cultured

1998
Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells.
    Brain research, 1998, Apr-20, Volume: 790, Issue:1-2

    The effect of stress on the production of cytokine-induced neutrophil chemoattractant (CINC) was examined in rat C6 glioma cells. We studied the production of CINC, an interleukin-8 (IL-8) family protein, with bacterial endotoxin, H2O2, and tumor necrosis factor-alpha (TNF-alpha). Each stress induced CINC mRNA in a concentration-dependent manner. Since stress activates the protein kinases regulating nuclear transcription factors, we examined the effects of protein kinase inhibitors and the over-expression of dominant-negative Ras on CINC mRNA expression. Neither over-expression of dominant-negative Ras nor pretreatment with PD98059 (MEK-1 inhibitor), SB203580 (p38MAPK inhibitor), or GF109203X (protein kinase C (PKC) inhibitor) altered stress-induced CINC mRNA expression. This suggests that the Ras-MAPK, p38MAPK, and PKC pathways are not involved in CINC mRNA expression in glial cells. On the other hand, pretreatment with herbimycin A, a potent tyrosine kinase inhibitor, or Ro31-8220, a non-selective serine/threonine kinase inhibitor, suppressed stress-induced CINC mRNA expression. This indicates that stress-induced CINC mRNA expression is mediated by herbimycin A-, or Ro31-8220-sensitive kinases in glial cells. Since stress activates NF-kappaB and NF-IL6, we examined that the effect of herbimycin A, which suppresses CINC mRNA expression, on NF-kappaB and NF-IL6 activation. Herbimycin A suppressed NF-kappaB but not NF-IL6. These results suggest that in rat glial cells, the factors that induce CINC mRNA expression are mediated by herbimycin A-sensitive NF-kappaB activation, but not through the PKC, Ras-MAPK or p38 MAPK pathways.

    Topics: Animals; Astrocytes; Benzoquinones; Calcium-Calmodulin-Dependent Protein Kinases; CCAAT-Enhancer-Binding Proteins; Chemokines, CXC; Chemotactic Factors; DNA-Binding Proteins; Enzyme Activation; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Enzymologic; Glioma; Growth Inhibitors; Growth Substances; Indoles; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lactams, Macrocyclic; Maleimides; Mitogen-Activated Protein Kinases; NF-kappa B; Nuclear Proteins; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Protein Kinase C; Quinones; ras Proteins; Rats; Rifabutin; RNA, Messenger; Signal Transduction; Transcription Factors; Tumor Cells, Cultured

1998
Herbimycin A suppresses NF-kappa B activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells.
    FEBS letters, 1995, Sep-11, Volume: 371, Issue:3

    Herbimycin A, a potent tyrosine kinase inhibitor, suppressed nitric oxide synthase (NOS) induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in C6 glial cells. LPS activated NF-kappa B, and this effect was inhibited by pretreatment with herbimycin A. In addition, IFN-gamma activated the tyrosine protein kinase, JAK2, and tyrosine-phosphorylation by itself was also inhibited by herbimycin A. These results suggest that herbimycin A suppresses iNOS induction by inhibition of both NF-kappa B activation caused by LPS, and tyrosine-phosphorylation of JAK2 caused by IFN-gamma in C6 glioma cells.

    Topics: Animals; Base Sequence; Benzoquinones; Enzyme Activation; Enzyme Induction; Enzyme Inhibitors; Glioma; Interferon-gamma; Janus Kinase 2; Lactams, Macrocyclic; Lipopolysaccharides; Molecular Sequence Data; NF-kappa B; Nitric Oxide Synthase; Oligodeoxyribonucleotides; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Quinones; Rats; Rifabutin; Tumor Cells, Cultured; Tyrosine

1995