Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of ornithine decarboxylase (ODC) enzyme activity occurs after exposure of hamster tracheal epithelial (HTE) cells to asbestos and the soluble tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Since active oxygen species are implicated as mediators of asbestos-induced biological responses studies here were designed to examine whether active oxygen species generated by asbestos or oxidants caused increased ODC activity. In confluent HTE cells, significant blockage of chrysotile or crocidolite asbestos-stimulated ODC activity occurred with simultaneous addition of catalase, but not superoxide dismutase, to medium. The addition of xanthine plus xanthine oxidase caused a dose-dependent increase in ODC activity, which was inhibited significantly after addition of catalase or mannitol, indicating that H2O2 was the principal oxidant produced in that reaction. Addition of phenazine methosulfate, a redox reagent used to generate superoxide, resulted in significant elevation of ODC, which was inhibited by addition of superoxide dismutase but not catalase. Hydrogen peroxide added to culture medium also caused a potent increase in ODC activity inhabitable by catalase. Hypochlorous acid caused increases in ODC activity, although the magnitude of this response was less than that observed with other oxidants. Therefore, although all active oxygen species examined triggered ODC, less reduced species (O2- and H2O2) were more proficient than OH or a halogenated oxidant. All oxidants, except HOCl, caused a significant increase in [3H] thymidine incorporation at 24 or 48 h after their addition to HTE cells. In comparative studies, exposure of HTE cells to either asbestos or xanthine plus xanthine oxide increased the level of ODC mRNAs proportionate to oxidant concentration and the extent of enzyme induction. Thus, data indicate that H2O2 plays a major role in asbestos-stimulated ODC induction and proliferation of epithelial cells of the respiratory tract by altering the regulation of a gene critical to proliferation.
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PMID:Role of asbestos and active oxygen species in activation and expression of ornithine decarboxylase in hamster tracheal epithelial cells. 184 7

1. Relationships between ornithine decarboxylase (ODC) and adenosine diphosphate ribosyl transferase (ADPRT) in human mononuclear leukocytes (HML) were tested by statistical comparisons of their values in a group of 46 people, and by use of inhibitors of ADPRT. 2. ODC was assayed following exposure of HML, for 20 hr, to mitogens [phytohemagglutinin (PHA) and pokeweed mitogen]; ADPRT was measured following exposure of HML to H2O2 (100 microM) for 1 hr (activated ADPRT), and in parallel cultures without H2O2 (constitutive ADPRT). 3. Significant correlations were found between ODC and ADPRT values; the effects of smoking disturbed the correlations. PHA induction of ODC was negatively influenced by age (standardized beta coefficient = -2.95, P = 0.005), while age also influenced ADPRT values negatively in non-smokers (for H2O2 activated ADPRT, standardized beta coefficient = -2.74, P less than 0.008). 4. Inhibitors of ADPRT, nicotinamide, caffeine and benzamide inhibited the induction of ODC by PHA in a concentration-dependent manner, in the range (0.6-10 mM) known to inhibit ADPRT.
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PMID:Mitogenic induction of ornithine decarboxylase in human mononuclear leukocytes: relationships with adenosine diphosphate ribosyltransferase. 213 20

In exponential-phase Chinese-hamster cells, 0.1 mM-diethyldithiocarbamate (DDC) afforded greater than 1 log survival protection to cultures treated before and during exposure to 1 mM-H2O2. Both DDC and H2O2 treatment stimulated the activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, within 4 h of exposure. DDC, and to a lesser degree H2O2, also stimulated the activity of spermidine N1-acetyltransferase (SAT), the rate-limiting enzyme in polyamine catabolism. The increase in SAT activity, after exposure to DDC or another stress (heat shock), was inhibited in cells depleted of putrescine and spermidine by alpha-difluoromethylornithine (DFMO), the enzyme-activated suicide inhibitor of ODC. Pretreatment with DFMO or heat shock also induced resistance to H2O2 cytotoxicity. Since SAT activity is low in resting cells, yet stimulation of enzyme activity depends on endogenous spermidine pools, these results suggest that the expression of SAT activity occurs by a mechanism involving a stress-dependent displacement of spermidine into a new intracellular compartment. The stimulation of ODC and SAT activities does not appear to be a necessary component of the mechanism by which DDC protects cells from H2O2 cytotoxicity, although spermidine displacement may be a common facet of the cellular response to stress.
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PMID:Effects of diethyldithiocarbamate and endogenous polyamine content on cellular responses to hydrogen peroxide cytotoxicity. 254 79

Since the enhancement of the activity of the natural glutathione (GSH)-dependent antioxidant protective system of the epidermal cells appears to inhibit the oxidative challenge presumably linked to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA), we have compared the effectiveness of diverse intracellular thiol delivery agents as inhibitors of the effects of TPA on GSH metabolism and ornithine decarboxylase (ODC; L-ornithine carboxylase, EC 4.1.1.17) induction in isolated mouse epidermal cells. Here we report at a 2-mM concentration, the monoethyl and monomethyl esters of GSH, N-acetyl-L-cysteine, and L-2-oxothiazolidine-4-carboxylate are all significantly more effective than GSH in inhibiting the sharp decline in the intracellular ratio of reduced GSH/oxidized glutathione (GSSG), the prolonged decrease in GSH peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.1.9) activity, and the induction of ODC activity caused by 1 microM TPA. Moreover, diethyldithiocarbamate prevents totally the initial drop in the GSH/GSSG ratio of TPA-treated cells and is the most potent inhibitor of TPA-decreased GSH peroxidase activity in relation with its remarkable 98% inhibition of TPA-induced ODC activity, suggesting that the potential antitumor-promoting activity of this compound in mouse skin may be far superior to that previously demonstrated by GSH in the initiation-promotion protocol.
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PMID:Effects of diverse intracellular thiol delivery agents on glutathione peroxidase activity, the ratio of reduced/oxidized glutathione, and ornithine decarboxylase induction in isolated mouse epidermal cells treated with 12-O-tetradecanoylphorbol-13-acetate. 303 95

Several structurally different tumor promoters altered to various degrees both glutathione (GSH) peroxidase (EC 1.11.1.9) and ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activities in mouse epidermis in vivo. At 5 h after their application to the skin, the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the stage 2 promoter mezerein were the most potent in inhibiting GSH peroxidase activity and inducing ODC activity. In comparison, the effects of anthralin, phorbol-12,13-didecanoate, benzoyl peroxide, H2O2, and phorbol-12,13-dibenzoate were much smaller, whereas the nontumor promoter phorbol, the hyperplastic agent ethyl phenylpropiolate, and the stage 1 promoter 4-O-methyl TPA did not alter GSH peroxidase and ODC activities. Various treatments including i.p. injections of 40 micrograms of Na2SeO3 and 100 mumol of GSH and/or topical applications of 40 mumol of D-alpha-tocopherol (vitamin E) 20 or 15 min, respectively, before tumor promoter treatment inhibited in an additive manner the effects of either TPA or mezerein on both GSH peroxidase activity and ODC induction. Moreover, these Na2SeO3, GSH, and/or vitamin E treatments inhibited in the same additive manner the tumor-promoting activity of TPA in the initiation-promotion protocol. However, when tested in the 2-stage promotion protocol with 4 doses of TPA followed by twice weekly applications of mezerein, Na2SeO3 plus vitamin E and GSH plus vitamin E treatments inhibited remarkably the tumor-promoting activity of mezerein but were ineffective in the first stage of promotion. The sequence and magnitude for the effects of 7,12-dimethylbenz[alpha]anthracene (DMBA) on GSH peroxidase and ODC activities were very different from those of the tumor promoters. In contrast with their antitumor-promoting activity, the treatments with Na2SeO3 plus vitamin E and GSH plus vitamin E failed to inhibit the carcinogenicity of a single large dose of DMBA and even enhanced the induction of skin tumors by repeated applications of subcarcinogenic doses of DMBA. These results suggest that the promoting component of DMBA carcinogenesis may be different from that of TPA. Moreover, the anticarcinogenicity of Na2SeO3, GSH, and vitamin E may be linked to their ability to facilitate or enhance the activity of the natural GSH-dependent antioxidant protective system of the epidermal cells during the later stages of skin tumor promotion.
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PMID:Effects of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin. 309 11

The induction of ornithine decarboxylase (ODC) activity in lymphocytes is associated with activation and the initiation of cellular proliferation. ODC is also an essential component in tumor promotion. Phorbol myristic acetate (PMA) is a mitogen for lymphocytes, but can also promote tumor formation. Tumor promotion is linked to the generation of free radicals induced by PMA. Modulation of intracellular glutathione is associated lymphocyte activation and in protection of cells from damage due to oxygen radicals. We examined the interaction between ODC activity and intracellular glutathione concentrations in EL4 murine lymphoblastoid cells. The intracellular glutathione concentration could be augmented in EL4 cells when cultured with the cysteine delivery agents 2-oxothiazolidine 4-carboxylate (OTC) and 2-mercaptoethanol (2-ME) and suppressed with the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine (BSO). OTC and 2-ME suppressed ODC activity in fresh serum and PMA-activated EL4 cells. BSO had no effect on ODC activity of EL4 cells cultured in the presence of PMA. While both OTC and 2-ME augmented the total intracellular glutathione concentration, PMA enhanced only the level of oxidized glutathione. To determine if the mechanism by which PMA or fresh serum altered intracellular glutathione and ODC activity was through the generation of oxygen radicals, EL4 cells were cultured with free radical scavengers. The nonpermeant electron acceptor potassium ferricyanide, and the H2O2 scavenger catalase, lowered ODC activity in both serum-stimulated and PMA-activated EL4 cells. Similarly, incubation of EL4 cells with either potassium ferricyanide or catalase elevated intracellular glutathione concentrations. These data suggest that (a) modulation of intracellular glutathione in the EL4 lymphoblastoid cell line alters ODC activity induced by fresh serum and by the mitogen PMA; (b) activation of EL4 cells by PMA alone alters intracellular glutathione metabolism, which may be associated with its role as a mitogen in lymphocyte activation; and (c) the generation of free radicals in EL4 cells may play a positive role in cellular activation.
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PMID:The generation of oxygen radicals: a positive signal for lymphocyte activation. 336 70

Garlic oil, onion oil and one of its constituents, dipropenyl sulfide, all increase, to diverse degrees, glutathione (GSH) peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.1.9) activity in isolated epidermal cells incubated in the presence or absence of the potent tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). The stimulatory effects of these oils on epidermal GSH peroxidase activity are concentration-dependent and long-lasting, and thus, abolish totally the prolonged inhibitory effect of TPA on this enzyme. Moreover, garlic oil (5 micrograms/ml) inhibits by about 50% TPA-induced ornithine decarboxylase (ODC, L-ornithine carboxy-lyase, EC 4.1.1.17) activity in the same epidermal cell system. This concentration of garlic oil also increases remarkably GSH peroxidase activity and inhibits ODC induction in the presence of various nonphorbol ester tumor promoters. Since the same oil treatments inhibit dramatically the sharp decline in the intracellular ratio of reduced (GSH)/oxidized (GSSG) glutathione caused by TPA, it is suggested that some of the inhibitory effects of garlic and onion oils on skin tumor promotion may result from their enhancement of the natural GSH-dependent antioxidant protective system of the epidermal cells.
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PMID:Effects of garlic and onion oils on glutathione peroxidase activity, the ratio of reduced/oxidized glutathione and ornithine decarboxylase induction in isolated mouse epidermal cells treated with tumor promoters. 380 49

The present study was undertaken to determine the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter known to inhibit superoxide dismutase (SOD) (superoxide: superoxide oxidoreductase, EC 1.15.1.1) and catalase (CAT) (H2O2: H2O2 oxidoreductase, EC 1.11.1.6) activities, on mouse epidermal glutathione (GSH) peroxidase (glutathione: H2O2 oxidoreductase, EC 1.11.1.9) activity in vivo and in vitro. TPA led to a rapid and transient increase in GSH peroxidase specific activity within 30 min followed by a decrease from 1 to 12 h. Incubation of isolated epidermal cells with GSH level-raising agents and/or selenium-containing compounds increased remarkably basal GSH peroxidase activity, and thus, abolished totally the prolonged inhibitory effects of TPA on this enzyme. The inhibitory effects of 0.2 mM cysteine (Cys) or 0.5 mM GSH and 2.5 microM Na2 SeO3 or 50 microM selenocystamine on TPA-decreased GSH peroxidase activity were additive, in relation with their additive inhibitory effects on TPA-induced ornithine decarboxylase (ODC) (L-ornithine carboxylase, EC 4.1.1.17) activity. These data support the hypothesis that the stimulators of the GSH-dependent antioxidant protective system of the epidermal cells may inhibit the oxidative challenge linked to skin tumor promotion by TPA.
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PMID:Inhibition of the effects of 12-O-tetradecanoylphorbol-13-acetate on mouse epidermal glutathione peroxidase and ornithine decarboxylase activities by glutathione level-raising agents and selenium-containing compounds. 399 2

Adriamycin (ADR) failed to inhibit and paradoxically enhanced the biological action of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo and in vitro. In the presence of ADR, the tumor promoter caused a greater sequential rapid increase and prolonged decrease in glutathione (GSH) peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.1.9) activity accompanied by a greater decrease in the ratio of reduced (GSH)/oxidized (GSSG) glutathione in isolated epidermal cells. The ability of ADR to deplete the intracellular level of GSH correlated with its ability to increase basal and TPA-induced ornithine decarboxylase (ODC, L-ornithine carboxylase, EC 4.1.1.17) activities. In vivo, topical ADR treatments also enhanced TPA-induced ODC activity as well as the tumor-promoting ability of TPA in the two-stage system of mouse skin carcinogenesis. Since lipid peroxidation has been associated with ADR toxicity, these data suggest that the enhancement of the tumor-promoting ability of TPA by ADR may be the result of an increased oxidative challenge that overwhelms the GSH-dependent antioxidant protective system of the epidermal cells.
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PMID:Enhancement by adriamycin of the effects of 12-O-tetradecanoylphorbol-13-acetate on mouse epidermal glutathione peroxidase activity, ornithine decarboxylase induction and skin tumor promotion. 407 83

Paraquat (methyl viologen, PQ) is a widely used herbicide that produces oxygen-derived free radicals and severely injures human lungs. In this study we examined the effects of PQ on the protein kinase C (PKC), ornithine decarboxylase (ODC) and c-jun oncogene expression in WI-38 human lung cells. Exposure of cells to 25-200 microM PQ resulted in an increase of [3H]phorbol dibutyrate (PDBu) binding and PKC redistribution in a dose-dependent manner. Interestingly, a superoxide dismutase mimic, 4-hydroxyl-2,2,6,6-tetramethyl-piperidine-1-oxyl (Tempol, 2.5 mM) and catalase (400 micrograms/ml) could significantly reduce the PQ-stimulated increase of phorbol ester binding and particular PKC phosphorylating activity, but dimethylsulfoxide (DMSO, 1.5%), an effective .OH trapping agent, failed to prevent this stimulation. In addition, an endogenous substrate of PKC, 80 kDa protein, was found to be highly phosphorylated in intact WI-38 cells treated with 50 microM PQ. The increase of phosphorylated proteins could be completely or partly abolished by Tempol or catalase, but only the phosphorylation of 80 kDa protein was diminished by protein kinase C inhibitor, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7). A maximal peak of ODC activity was observed at 6 h of treatment with 50 microM PQ. PQ induced activity was reduced at the following rates, Tempol 85%, DMSO 80% and catalase 45%, but H-7 failed to do so. Furthermore, we found that the level of c-jun mRNA was transiently increased by PQ and the peak appeared at 1 h of treatment. When correlated with the PKC result, Tempol, catalase and H-7 all effectively blocked PQ-elicited c-jun transcript expression, but DMSO only exhibited a weakly inhibitory effect. We therefore propose that superoxide anion (O2- and H2O2 generated by PQ could activate PKC and lead to induction of c-jun gene expression; on the other hand, O2- and .OH might trigger other kinase pathways to elevate ODC activity. Finally, the sequential expression of c-jun oncogene and ODC may cooperate to relieve the oxidative damages elicited by PQ.
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PMID:Pronounced activation of protein kinase C, ornithine decarboxylase and c-jun proto-oncogene by paraquat-generated active oxygen species in WI-38 human lung cells. 766 13


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