Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of C2 and factor B, the key components of complement system, is performed by various kinds of cells and is also up-regulated by interferon-gamma (IFN-gamma). By using human fibroblasts, human glioblastoma cell line A172 and monocytes, we investigated the signal-transduction mechanism for IFN-gamma-induced synthesis of C2 and factor B. The C2 and factor B synthesis induced by IFN-gamma in all three cell types was inhibited by a protein kinase C (PKC) inhibitor, 1-(5-isoquinolinyl-sulphonyl)-2-methylpiperazine (H-7). The depletion of PKC in these cell types after treatment with phorbol 12-myristate 13-acetate (PMA) resulted in inhibition of IFN-gamma-induced C2 production. In addition, IFN-gamma treatment elicited a decrease in cytoplasmic PKC in A172 cells, indicating that PKC is activated by IFN-gamma. These results suggest that PKC is crucial for IFN-gamma-induced C2 and factor B synthesis. Northern-blot analysis showed that the effects at H-7 were at least partly mediated by modulation of C2 and factor B mRNA abundance in A172 cells. Since treatment of fibroblasts and A172 cells with IFN-gamma had no effect on intracellular Ca2+ concentration, and since neither EGTA nor nifedipine inhibited C2 or factor B synthesis induced by IFN-gamma, we concluded that intracellular Ca2+ mobilization was not involved in the effect of IFN-gamma. In addition, genistein, herbimycin A and N-(6-aminohexyl)-5-chloro-1-naphthalene-sulphonamide (W-7) had no inhibitory effect on IFN-gamma-mediated action in any of the three cell types, which suggests that IFN-gamma acts independently of tyrosine kinases and calmodulin-dependent protein kinases.
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PMID:Role of protein kinase C activation in synthesis of complement components C2 and factor B in interferon-gamma-stimulated human fibroblasts, glioblastoma cell line A172 and monocytes. 783 55

We examined the effects of several kinds of protein kinase inhibitors against calcium/phospholipid-dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA) on heat-induced hsp72 gene expression in a human glioblastoma cell line (T98G) as a source of insight into the type of protein kinase contributing to its gene expression. When the cells were treated with 1-(5-isoquinolinesulphonyl)-2-methylpiperazine [(H7) a potent inhibitor of PKC, PKA, and others], the suppression of heat-induced Hsp72 accumulation was observed. Heat-induced Hsp72 accumulation was also suppressed by staurosporine (a potent inhibitor of PKC and PKA) or calphostin C [(CAL) a potent inhibitor of PKC] at high concentration (10 x IC50) but not at low concentration (1 x IC50). N-(2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide [(H89) a potent inhibitor of PKA] did not affect heat-induced Hsp72 accumulation at either low (1 x IC50) or high concentrations (10 x IC50). Combination treatment with CAL and H89 suppressed the heat-induced Hsp72 accumulation more strongly than did treatment with either inhibitor alone. Furthermore, the heat-induced DNA-binding activation of heat-shock factor (HSF) was suppressed by CAL at high concentration (10 x IC50), and combination treatment with CAL and H89 showed stronger suppression. In the H7 treatment, the clear suppression of HSF activation was observed even at low concentration (1 x IC50). In addition, the cellular content of Hsp72 increased after the treatment of PKC or PKA activator. These results suggest that not only PKC, but also PKA may play an important role in heat-induced hsp72 gene expression.
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PMID:Effects of protein kinase inhibitors on heat-induced hsp72 gene expression in a human glioblastoma cell line. 961 83

We investigated the effects of a protein kinase (PK) inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), on the regulation of heat shock protein (hsp)72 gene expression in a human glioblastoma cell line (A-172) using a gel mobility-shift assay and Western blot analysis. Heat shock transcription factor 1 (HSF1) was phosphorylated immediately after heat treatment (44 degrees C, 30 min) and the phosphorylation of HSF1 was suppressed by H-7. The increase in DNA binding ability of HSFI to heat shock element (HSE) by heat shock was significantly suppressed by the addition of H-7 in a dose-dependent manner. Similarly, the accumulation of hsp72 by heat shock was suppressed by the addition of H-7 in a dose-dependent manner. Since H-7 is known to be a potent inhibitor of some PKs, especially calcium-dependent PK (PKC), cyclicAMP-dependent PK (PKA) and cyclicGMP-dependent PK (PKG), it is possible that the activation of HSF1 by phosphorylation and subsequent hsp72 gene expression are dependent on some of those PKs. The nature of H-7 as a non-specific inhibitor for PKs is discussed in relation to its availability for regulation of heat sensitivity of cells depending on cellular level of hsp72.
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PMID:The protein kinase inhibitor, H-7, suppresses heat induced activation of heat shock transcription factor 1. 1048 32