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)

We have compared some mechanisms involved in the defense against doxorubicin-induced free radical damage in rat hepatoma and glioblastoma cell lines and their doxorubicin-resistant variants presenting an overexpression of the multidrug resistance gene. Immediate in vivo production of malondialdehyde was minor and was not different in sensitive and resistant cells. Alpha-tocopherol was undetectable in all cell lines. Glutathione levels were not different in sensitive and resistant cells and these levels did not vary upon doxorubicin treatment. Resistant cells exhibited either a 50% decrease (hepatoma) or a 25% increase (glioblastoma) of glutathione-S-transferase activity. Glutathione reductase presented no important change upon acquisition of resistance. In contrast, selenium-dependent glutathione peroxidase activity was consistently 2-6-fold increased in the resistant cells, which suggests a magnification of protection mechanisms against hydroxyle radical formation from H2O2 in resistant cells. Depletion of glutathione levels by buthionine sulfoximine sensitized hepatoma resistant cells to doxorubicin, but had no effect on doxorubicin cytotoxicity to glioblastoma cells.
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PMID:Development of mechanisms of protection against oxidative stress in doxorubicin-resistant rat tumoral cells in culture. 196 16

Oxidation of catecholamines may lead to the formation of o-semiquinones and o-quinones in catecholaminergic brain tissues, and these reactive molecules may form DNA or protein adducts. In this study, cultured cells were treated with dopamine (DA) for 24 h and 32P-postlabelling was used to detect DA-DNA adducts. In HL-60 cells, 250 microM DA induced 8.5 DNA adducts/10(8) nucleotides; adduct formation was dose-dependent up to 500 microM DA. Addition of H2O2 increased the relative adduct levels 7- to 13-fold, but no adducts were detected when DA and ascorbic acid were added simultaneously. In human glioblastoma cell lines U87, U251, SF-763 and SF-767, 1000 microM DA produced 0.98-2.31 adducts/10(8) nucleotides. These results suggest that the formation of DNA adducts by DA may contribute to the development of certain neurodegenerative diseases such as Parkinson's disease.
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PMID:Detection of dopamine--DNA adducts: potential role in Parkinson's disease. 850 13

Protein tyrosine phosphorylation was examined on a human glioblastoma cell line, T98G, after exposure to oxidative stress in vitro. Hydrogen peroxide (1 mM) markedly induced tyrosine phosphorylation of a 125 kDa protein at 30 min after stimulation. The 125-kDa molecule phosphorylated was revealed to be a focal adhesion kinase (FAK). Tyrosine phosphorylation of p125FAK continued at least up to 5 h, and decreased after 8 h concomitant with apoptosis. Tyrosine phosphorylation of p125FAK was blocked by herbimycin A, a potent inhibitor of protein tyrosine kinases, while apoptosis was accelerated. When T98G cells were incubated with FAK antisense oligonucleotide, apoptosis was also accelerated. These results suggest that tyrosine phosphorylation of p125FAK plays a suppressive role in hydrogen peroxide-induced apoptosis.
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PMID:A suppressive role of p125FAK protein tyrosine kinase in hydrogen peroxide-induced apoptosis of T98G cells. 943 84

We have monitored glial cell line-derived neurotrophic factor (GDNF) secretion from rat C6 glioblastoma cells by ELISA. Representative cytokines, neurotrophins, growth factors, neuropeptides, and pharmacological agents were tested for their ability to modulate GDNF release. Whereas most factors tested had minimal effect, a 24-h treatment with fibroblast growth factor-1, -2, or -9 elevated secreted GDNF protein levels five- to 10-fold. The proinflammatory cytokines interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and lipopolysaccharide elevated GDNF release 1.5- to twofold. Parallel studies aimed at elucidating intracellular events that may regulate GDNF synthesis/release demonstrated the involvement of multiple signaling pathways. GDNF levels were increased by phorbol 12,13-didecanoate (10 nM) activation of protein kinase C, the Ca2+ ionophore A23187 (1 microM), okadaic acid (10 nM) inhibition of type-2A protein phosphatases, nitric oxide donors (1 mM), and H2O2 (1 mM)-induced oxidative stress. Elevation of cyclic AMP levels by either forskolin (10 microM) or dibutyryl cyclic AMP (1 mM) repressed GDNF secretion, as did treatment with the glucocorticoid dexamethasone (1 microM). Our results demonstrate that diverse biological factors are capable of modulating GDNF protein levels and that multiple signal transduction systems can regulate GDNF synthesis and/or release.
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PMID:Regulation of glial cell line-derived neurotrophic factor release from rat C6 glioblastoma cells. 945 47

Overexpression of the bcl-2 and the related bcl-xL protooncogene proteins enhance cell survival by inhibiting apoptosis induced by many agents including oxidants. Whether these proteins contribute to survival in oxidant-resistant cells is not known. The current study assessed the expression of bcl-2 and bcl-xL proteins in human glioblastoma U87MG cells and human lung adenocarcinoma A549 cells selected for resistance to 0, 50, 100, 200, and 400 microM H2O2 by exposure to this oxidant one time each passage for 9 months. When examined 7 to 32 days after cessation of peroxide exposure (times when peroxide resistance was maintained), bcl-2 protein levels were significantly increased in most peroxide-resistant U87MG cells. However, the increase was not dose dependent and was not accompanied by an increase in mRNA levels. A549 cells did not express significant levels of bcl-2 protein, although bcl-2 mRNA was detectable. A549 cells expressed large amounts of bcl-xL and immunohistochemistry demonstrated extensive localization of this protein around the nucleus. However, expression of this protein was not altered in peroxide-resistant lines nor was bcl-2 protein increased to a measurable level. U87MG cells also expressed bcl-xL but it was not altered in peroxide-resistant cells. Although the increased bcl-2 protein in peroxide-resistant U87MG cells may contribute to their oxidant tolerance, the lack of a dose-response relationship, the failure to induce bcl-xL protein, and the absence of any bcl-2 or bcl-xL protein induction in peroxide-resistant A549 cells suggest these genes are not primary factors in oxidant resistance.
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PMID:Bcl-2 and Bcl-xL in peroxide-resistant A549 and U87MG cells. 957 23

The relation between the intracellular glutathione (GSH) concentration and hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. The intracellular GSH concentration in human glioblastoma (T98G, U87MG) and glioma (KG1C) cell lines was one or two orders of magnitude higher than that in a human myelogenous leukemic cell line (HL-60), which showed higher sensitivity to H2O2. Pretreatment of these cell lines with L-buthionine-[S,R]-sulfoximine, which significantly reduced the intracellular GSH concentration, increased their sensitivity against H2O2, whereas pretreatment with N-acetyl-L-cysteine, which did not significantly change the intracellular GSH concentration, only marginally protected the cells from the cytotoxic effect of H2O2. The results suggest that drug sensitivity of tumor cells can be modified by glutathione-modulating compounds.
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PMID:Effect of glutathione-modulating compounds on hydrogen-peroxide-induced cytotoxicity in human glioblastoma and glioma cell lines. 962 Feb 20

It has been shown that astrocytes (human glioblastoma U118 cell line) release reactive oxygen species (ROS), including superoxide O2.- and hydrogen peroxide H2O2 following the action of C5a complement component C5a (but not C3a). The effect of C5a (1 nM) is accompanied with hyperpolarization of the astrocyte plasma membrane. Component C3a (100 nM), which is not an inducer of ROS, caused a prolonged depolarization of astrocytes. However, both the agents induced a transient increase in intracellular Ca2+ concentration. The data obtained permit a conclusion that O2.- participates in the intracellular signal transduction, and is involved in the mechanism of hyperpolarization response of astrocytes to the effect of the inducer of ROS, complement component C5a.
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PMID:[Activation of astrocytes of by anaphylatoxins of the complement system]. 982 Dec 47

It is now generally accepted that massive neuronal death due to oxidative stress is a regular feature of brains in neurodegenerative diseases. However, much less attention has been given to the death of glial cells. In this study, we examined p53-sensitive apoptosis of cells by using human glioblastoma A172 cells and p53-deficient mouse astrocytes. In human A172 cells, hydrogen peroxide (H2O2) caused cell death in a time- and concentration-dependent manner, accompanied by nucleosomal DNA fragmentation and chromatin condensation. After treatment with H2O2, p53 protein was highly expressed and protein levels of Bak, p21WAF1/CIP1 and GADD45 were also enhanced. However, the protein levels of Bcl-2 and Bax did not change. On the other hand, primary cultured astrocytes from p53-deficient mouse brain grew faster than wild-type and heterozygous astrocytes. In addition, p53-deficient astrocytes were more resistant to H2O2-induced apoptosis than wild-type and heterozygous astrocytes. These results suggest that glial proliferation and the repair of damaged DNA may be regulated by p53-induced p21WAF1/CIP1 and GADD45, and that glial apoptosis caused by oxidative stress may be mediated by p53-induced Bak.
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PMID:Hydrogen peroxide-induced apoptosis mediated by p53 protein in glial cells. 989 Jun 30

Protein phosphorylation in a human glioblastoma cell line, T98G, was examined after exposure to oxidative stress in vitro. Hydrogen peroxide (1 mM) markedly induced tyrosine phosphorylation of focal adhesion kinase (FAK) and serine phosphorylation of Akt at 1 h after stimulation. Concommitantly, the association of FAK with phosphatidylinositide 3'-OH-kinase (PI 3-kinase) was also observed by the hydrogen peroxide stimulation. When T98G cells were incubated with wortmannin, a PI 3-kinase inhibitor, both PI 3-kinase activity and phosphorylation of Akt were inhibited, whereas apoptosis by oxidative stress was accelerated. Concomitant with apoptosis, elevated level of CPP32 protease activity (caspase-3) was observed, with decreases in Bcl-2 protein and increases in Bax protein. These results suggested that in the signal transduction pathway from FAK to PI 3-kinase, Akt promotes survival. Thus, it became apparent that FAK is the upstream signal protein of the PI 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis in T98G cells.
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PMID:FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line. 1018 51

Hydrogen peroxide (H2O2) induced internucleosomal DNA cleavage in human myelogenous leukemic cell lines (HL-60, ML-1, THP-1, U-937), but not in human glioblastoma (T98G, U87MG) and glioma (KG1C) cell lines. However, H2O2 produced apoptotic cells, characterized by cell shrinkage, nuclear fragmentation and chromatin condensation in glioblastoma and glioma cell lines. Autodigestion experiments revealed that the major endonucleases, present in all leukemic, glioblastoma and glioma cell lines, were divalent cation-independent endonuclease(s). The endonudease(s) present in the lysates of all these cells were activated at acidic, but not at neutral pH. The results suggest that the endonuclease activity might be differently regulated between leukemic and glioma cell lines.
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PMID:Endonuclease activity and hydrogen peroxide-induced cytotoxicity in human glioblastoma and glioma cell lines. 1036 81


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