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

Differences in nuclear composition and variations in the types of acid soluble nuclear proteins were identified when cultivated neoplastic and nontransformed rat brain cells were compared. HeLa S-3 cells were used as a biological reference in these studies. The nuclei of anaplastic glioma cells were found to contain more total nuclear protein and greater amounts of nuclear RNA, than the nuclei of nontransformed embryonic and neonatal rat brain cells. Densitometer profiles of samples developed by polyacrylamide gel electrophoresis indicated that all three major histone classes were present in the nuclei of the four different cell types examined. Each type of cell was grown in the presence of 3H-lysine or 3H-lysine plus 14C-arginine to further characterize both the histones and the acid soluble nonhistone proteins. Neoplastic and nontransformed cells contained similar quantities of histones H4, H3, H2A and H2B. In contrast, transformed cells were found to contain two dominant subspecies of lysine rich H1 histone, while only one histone H1 subcomponent was extracted from the nuclei of the embryonic and neonatal rat brain cells. Nuclei isolated from HeLa cells and anaplastic glioma cells also contained increased varieties and larger quantities of acid soluble nonhistone nuclear proteins.
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PMID:Comparative aspects of nuclear proteins and nuclear composition of cultivated embryonic, neonatal and neoplastic rat brain cells of glial origin. 46 86

The role of protein kinase C in migration of tumor cells from spheroid cultures was investigated using parental rat glioma cells and their TPA resistant counterparts. These two lines differed in their PKC content as judged by the histone phosphorylation method. Also 4 days of treatment with IRA led to PKC down-regulation. Cells having a drastically decreased PKC level migrated better than those having a normal PKC content.
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PMID:The role of protein kinase C in migration of rat glioma cells from spheroid cultures. 156 92

We have studied the effect of butyrate and other short-chain fatty acids on thyroid hormone nuclear receptors in C6 cells, a rat glioma cell line. Exposure of C6 cells to butyrate leads to increased levels of L-triiodothyronine (T3) in the nuclear and extranuclear compartments. The rise in nuclear binding is not merely a reflection of the higher cellular hormone content, and Scatchard analysis of T3 binding to isolated nuclei reveals that butyrate increases receptor number without changing affinity. The effect on the receptor is quantitatively important: a 48-h incubation with 2 mM butyrate increases nuclear binding by 2-3-fold, and 5 mM butyrate by 3-5-fold. Other short-chain fatty acids were found to similarly influence both nuclear receptor and extranuclear T3 levels with the following potency: butyrate greater than valerate greater than propionate greater than acetate. On the contrary, ketone bodies were ineffective. Butyrate increases receptor levels by decreasing receptor degradation, since the apparent t1/2 of receptor disappearance increased by approximately 3-fold in cells incubated with 2 mM butyrate for 48 h. The regulation of receptor number might be secondary to an action of butyrate on regions of the chromatin to which the receptor associates. We then examined the effect of butyrate on histone acetylation. The fatty acid had little effect in increasing the level of multiacetylated forms of H3 and H4 histone when studied in acid-urea gels, but it markedly inhibited the turnover of [3H] acetate from the histone fraction. There was a striking similarity in the dose-response of butyrate for increasing receptor levels and inhibiting histone deacetylation. Furthermore, a very close correlation between receptor levels and [3H]acetate release was also found when different short-chain fatty acids were used. We thus conclude that the effect of butyrate on the receptor could be explained by a modification of the chromatin structure of C6 cells secondary to acetylation.
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PMID:Modulation of thyroid hormone nuclear receptors by short-chain fatty acids in glial C6 cells. Role of histone acetylation. 377 18

beta-Adrenergic receptors and the activities of adenylate cyclase, phosphodiesterase and protein kinase were examined in two human glioma cell lines, U 251 and LM, as well as in rat C6 glioma. [3H]Dihydroalprenolol binding to beta-adrenergic receptors was specific, saturable and of high affinity in each cell line. The dissociation constant (Kd) and maximal binding (Bmax) extrapolated from Scatchard curves were Kd = 17.4 +/- 3.2 nM and Bmax = 1110 +/- 197 fmol/mg protein for the U-251 cells; Kd = 14.4 +/- 2.2 nM and Bmax = 655 +/- 105 fmol/mg protein for the LM cells; and Kd = 5.6 +/- 1.1 nM and Bmax = 454 +/- 80 fmol/mg protein for the C6 glioma cells. L-Isoproterenol stimulated cyclic AMP formation in all 3 cell lines. beta-Adrenergic agonists also increased calcium-dependent and calcium non-dependent phosphodiesterase activity in these tumor cells. Cytosolic protein kinase in the 3 cell lines phosphorylated exogenous histone as a substrate. The phosphorylation was enhanced by cyclic AMP. Cytosolic protein kinase also phosphorylated endogenous cytosolic macromolecules. The phosphorylated proteins had molecular weights of 30,000, 51,000 and 90,000 in the two human glioma cell lines. The present results indicate that human glioma cell lines have functional beta-adrenergic receptors linked to adenylate cyclase. These beta-receptors can also regulate phosphodiesterase activity and cyclic AMP in human glioma cells can activate protein kinase and induce the phosphorylation of specific proteins.
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PMID:The beta-adrenergic receptor system in human glioma-derived cell lines: the mode of phosphodiesterase induction and the macromolecules phosphorylated by cyclic AMP-dependent protein kinase. 632 58

Protein kinase C (PKC), the major receptor for tumor-promoting phorbol esters, consists of a family of at least 12 distinct lipid-regulated enzymes. We examined the expression and regulation of PKC isoforms in C6-glioma and NG 108-15 hybrid cells. Western blot analysis indicated that both cell lines express four PKC isoforms, PKC alpha, PKC delta, PKC epsilon and PKC zeta. The expression of PKC alpha and PKC delta in C6-glioma cells was more abundant than NG 108-15 cells, however, PKC epsilon in NG 108-15 was more abundant than C6-glioma cells in which PKC epsilon was almost undetectable. Treatment of both cells with TPA for 10 min resulted in the translocation of PKC alpha, PKC delta and PKC epsilon to the membrane fraction. When the intact cells were treated with Ca(2+)-free, EGTA containing physiological saline solution, the membrane bound conventional PKC alpha (cPKC alpha) was greatly reduced and cytosolic cPKC alpha was only slightly increased. However, neither membrane bound nor cytosolic new PKC delta (nPKC delta), nPKC epsilon and atypical PKC zeta (aPKC zeta) was affected by extracellular Ca2+ depletion. In this condition, the translocation of cPKC alpha, nPKC delta and nPKC epsilon induced by TPA still occurred, however, that of cPKC alpha was reduced more than in the normal condition. After long-term treatment (17 h) with TPA, cPKC alpha, nPKC delta and nPKC epsilon were down-regulated both in the cytosol and membrane. The phenomena of cPKC alpha were confirmed by measuring the PKC activity with histone as the substrate. From in vitro endogenous phosphorylation studies, a 31 kDa substrate protein phosphorylation in C6 glioma cell membrane and 31 and 26 kDa proteins in NG 108-15 cell membrane were increased in the translocation but disappeared in the down-regulation of PKC.
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PMID:Differential expression of protein kinase C isoforms in glial and neuronal cells. Translocation and down-regulation of PKC isoforms in C6 glioma and NG 108-15 hybrid cells: effects of extracellular Ca(2+)-depletion. 749 43

Cells expressing the herpes simplex-thymidine kinase (HS-TK) gene as a consequence of retroviral transduction, as well as TK-negative (TK-) bystander cells, can be killed by treatment with ganciclovir (GCV). In vitro, this "bystander effect," has been attributed to metabolic cooperation through gap junctions or to the uptake of apoptotic vesicles. We show that GCV treatment kills TK-negative U-87 glioma cells cocultured with cells that express TK (TK+) but that have lost the capacity for releasing retroviral particles. A photometric enzyme immunoassay identifies histone-associated DNA fragments, typical of apoptosis, in the cytosol of GCV-treated TK+ cells, and apoptotic features are also demonstrated by ultrastructural studies. Northern blot analysis and the reverse transcription polymerase chain reaction (PCR) show that connexin 43, a major constituent of gap junctions, is expressed in TK+ and U-87 cells. The size of U-87 tumors in nude mice subsequently injected with TK+ cells and GCV is not significantly different than in untreated animals; whereas, after injecting 1:1 mixtures of U-87 and TK+ cells, GCV treatment only causes a temporary regression of tumor growth. On the contrary, when the injected mixtures contain PA317.STK.SBA (a retroviral producer cell line that can transduce efficiently the HS-TK gene) and U-87 cells, tumors are destroyed effectively by GCV treatment. Thus, an experimental setting in which U-87 gliomas are matched with cells that are able to express, but not to transduce, the HS-TK gene indicates that the bystander effect kills U-87 cells in vitro by mechanisms associated with apoptotic death. In vivo, this effect is not sufficient to restrain the tumor growth taking place in immunodeficient animals.
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PMID:The "bystander effect": association of U-87 cell death with ganciclovir-mediated apoptosis of nearby cells and lack of effect in athymic mice. 754 76

Removal of histones and other nuclear proteins greatly enhances the sensitivity of mammalian cells to DNA damage by ionizing radiation. We examined the possibility that the ease of dissociation of histones, or the association of other nuclear proteins with DNA, may differ between radioresistant and sensitive human tumor cells. Cells embedded in agarose were exposed to increasing salt concentrations prior to irradiation and examination using a microscopic gel electrophoresis method, the neutral comet assay. Induction of double-strand breaks increased by a factor of about 20 when cells of four human tumor cell lines, HT144 melanoma, HT29 adenocarcinoma, DU145 prostate carcinoma and U87 glioma, were exposed to 2 M NaCl prior to irradiation. Subtle differences in sensitivity to induction of double-strand breaks by radiation between cells of the four cell lines were also observed after extraction with 0.7-1.1 M NaCl; however, no correlation with radiosensitivity was apparent. While a significant number of histone and non-histone proteins are present after extraction with 1.2 M NaCl, these proteins apparently have only a minor influence on radiosensitivity. However, if they are allowed to remain with DNA during electrophoresis, about 15 times more strand breaks are required to produce a similar amount of DNA migration in both DU145 and HT144 cells. These results suggest that the association between proteins and DNA within the nucleus, as probed by extraction with sodium chloride, does not help to explain differences in intrinsic radiosensitivity among cells of these diverse tumor cell lines.
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PMID:Radiation-induced DNA double-strand breaks produced in histone-depleted tumor cell nuclei measured using the neutral comet assay. 772 28

Chromatin condensation during apoptosis induced by TGF beta 1 in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells was examined and compared with that occurring during mitosis. Apoptotic (round-up) cells were selectively detached from the culture surface by a mechanical shock. Their histones were analysed in comparison with those obtained from TGF beta 1-treated cells remaining attached to the culture surface, from control cells not treated with TGF beta 1 and from metaphase cells. While mitosis-specific hyperphosphorylation of histones H1 and phosphorylation of histone H3 was not observed in apoptotic cells, apoptotic chromatin lacked ubiquitinated histone H2A (histone uH2A) as did metaphase chromosomes. The cellular level of free ubiquitin and the overall pattern of ubiquitin-conjugated proteins were, however, found to remain unaltered in apoptotic cells, suggesting that the ubiquitin conjugating machinery for histone H2A may be specifically perturbed during the chromatin condensation occurring in apoptosis.
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PMID:Disappearance of ubiquitinated histone H2A during chromatin condensation in TGF beta 1-induced apoptosis. 776 93

The rates of synthesis of histone H1 subtypes in synchronized mouse NIH 3T3 fibroblasts were compared with those of rat C6 glioma cells during the G0, G1, and S phases by using a combination of HPLC techniques and conventional gel electrophoresis. In the mouse cell line, all H1 subtypes, H1a-H1e including histone H1(0), were detectable. In the rat cell line, however, no histone H1a was found. H1c and H1e from both cell lines show in the quiescent state a relatively high specific activity comparable with that of H1(0). After release from the G0/G1 block, the synthesis of H1(0) and likewise that of H1c and H1e increase for a short period. All H1 subtypes have their maximum specific activity at the same time after stimulation. The percentage of total H1 specific activity of H1a, H1b, and H1d increases, those of H1c and H1e remain relatively constant, and that of H1(0) decreases while cells cycle from the G0/G1 to the S phase. These findings support our assumption that H1 subtypes could be classified into three groups with common metabolic characteristics: one consists of H1a, H1b, and H1d; another of H1c and H1e; and a third of H1(0) histone. Moreover, the corresponding H1 subtypes from two different species seem to have similar specific activities during the G1 and S phases.
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PMID:G1- and S-phase synthesis of histone H1 subtypes from mouse NIH fibroblasts and rat C6 glioma cells. 842 46

In vivo phosphorylation of the five histone H1 variants H1a-H1e including H1(0) in NIH 3T3 mouse fibroblasts was examined during the cell cycle by using a combination of HPLC techniques and conventional AU gel electrophoresis. Phosphorylation starts during the late G1 phase and increases throughout the S phase. In the late S phase, the H1 variants exist as a combination of molecules containing 0 or 1 (H1a, H1c), 0-2 (H1d), or 0-3 (H1b, H1e) phosphate groups with a share of unphosphorylated protein ranging between 35% and 75%, according to the particular subtype. Pulse-chase experiments show that phosphorylation during the S phase is a dynamic phosphorylation process with a limited phosphorylation maximum. In most H1 subtypes, phosphorylation occurs very rapidly at the G2/M transition with only small amounts of intermediate phosphorylated molecules. Phosphorylation of mouse H1c, however, occurs stepwise during this transition. Phosphorylated mouse histone subtypes from cells in mitosis contain four phosphate groups in the case of H1a, H1c, and H1e and five in the case of H1b and H1d. Comparison of the mouse phosphorylation pattern to that in rat C-6 glioma cells showed differences for H1e and H1d. By comparing the different phosphorylation patterns of the individual H1 variants during the cell cycle, we were able to classify the H1 histones into subtypes with low (H1a, H1c, H1(0)) and high (H1b, H1d, H1e) phosphorylation levels.
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PMID:In vivo phosphorylation of histone H1 variants during the cell cycle. 863 56


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