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)

Non-metabolizable analogues of glucose, including 1-O-methyl alpha-D-glucopyranoside (alpha MDG), that are co-transported with Na+ increase the specific activity of ornithine decarboxylase (ODC) in LLC-PK1 cells [Lundgren and Vacca (1990) Am. J. Physiol. 259, C647-C653]. The present study examines the effect of alpha MDG on LLC-PK1-cell ODC mRNA expression. The relative concentration of ODC mRNA in cells incubated in Earle's balanced salts solution minus glucose (EBSS--G) plus 3 mM alpha MDG was 5-6-fold higher than the concentration of ODC mRNA in cells incubated in either EBSS--G alone or in EBSS--G plus 3 mM 3-O-methyl-D-glucopyranose, a non-metabolizable analogue of glucose that is taken up by a passive carrier-mediated glucose transporter. Actinomycin D and cycloheximide completely blocked the increase in ODC activity induced by alpha MDG. Actinomycin D was also a potent inhibitor of ODC mRNA expression by alpha MDG. Cycloheximide had very little effect on the ability of this sugar to increase ODC mRNA. The relative concentration of ODC mRNA increased as a function of the incubation time in EBSS--G plus alpha MDG. The amount of ODC mRNA also increased as a function of the concentration of alpha MDG in EBSS--G. The addition of phlorizin (100 microM) to EBSS--G prevented alpha MDG from increasing ODC mRNA in LLC-PK1 cells. Phlorizin did not prevent phorbol 12-myristate 13-acetate (PMA) from enhancing LLC-PK1-cell ODC mRNA expression. The positive effect of both alpha MDG and TPA on ODC mRNA expression was suppressed when cells were incubated in hypertonic EBSS--G. From these results it is suggested that the uptake of Na(+)-dependent cotransported sugars increase ODC activity by enhancing ODC gene transcription and that this process may be dependent on cell volume expansion.
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PMID:Sodium-dependent co-transported analogues of glucose stimulate ornithine decarboxylase mRNA expression in LLC-PK1 cells. 843 72

This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems. Emphasis is placed upon the anticarcinogenic activity of these polyphenols and their proposed mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Tea is manufactured as either green, black, or oolong; black tea represents approximately 80% of tea products. Epidemiological studies, though inconclusive, suggest a protective effect of tea consumption on human cancer. Experimental studies of the antimutagenic and anticarcinogenic effects of tea have been conducted principally with green tea polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although several GTPs possess anticarcinogenic activity, the most active is (-)-epigallocatechin-3-gallate (EGCG), the major constituent in the GTP fraction. Several mechanisms appear to be responsible for the tumor-inhibitory properties of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of chemically induced lipid peroxidation; inhibition of irradiation- and TPA-induced epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities; inhibition of protein kinase C and cellular proliferation; antiinflammatory activity; and enhancement of gap junction intercellular communication. Curcumin is the yellow coloring agent in the spice tumeric. It exhibits antimutagenic activity in the Ames Salmonella test and has anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in the breast and colon and neoplastic lesions in the skin, forestomach, duodenum and colon of rodents. In addition, curcumin inhibits TPA-induced skin tumor promotion in mice. The mechanisms for the anticarcinogenic effects of curcumin are similar to those of the GTPs. Curcumin enhances glutathione content and glutathione-S-transferase activity in liver; and it inhibits lipid peroxidation and arachidonic acid metabolism in mouse skin, protein kinase C activity in TPA-treated NIH 3T3 cells, chemically induced ODC and tyrosine protein kinase activities in rat colon, and 8-hydroxyguanosine formation in mouse fibroblasts. Ellagic acid is a polyphenol found abundantly in various fruits, nuts and vegetables. Ellagic acid is active in antimutagenesis assays, and has been shown to inhibit chemically induced cancer in the lung, liver, skin and esophagus of rodents, and TPA-induced tumor promotion in mouse skin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Polyphenols as cancer chemopreventive agents. 853 95

Anticarcinogenic action of beta-carotene was analyzed with determination of ornithine decarboxylase (ODC) activity induced by TPA and a two-stage model of skin papilloma-genesis in mice. Results showed increase of ODC activity induced by TPA could be significantly inhibited, onset of tumor postponed, and number of tumor foci decreased by beta-carotene. It suggested beta-carotene had an obvious chemoprophylactic effect on tumor.
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PMID:[Inhibition of ornithine decarboxylase activity and epidermal papilloma in mice by beta-carotene]. 869 43

In this study, we examined the cutaneous effects of tacalcitol [1,24(R)(OH)2D3] on epidermal proliferation, differentiation, and skin inflammation in vivo using hairless mice. Tacalcitol was shown to inhibit epidermal proliferation using TPA-induced ornithine decarboxylase activity and DNA synthesis as indices, and the induction of epidermal differentiation using type I transglutaminase activity as an index. Tacalcitol also displayed an antiinflammatory effect on TPA-induced inflammatory changes histopathologically. These results confirm the clinical efficacy of tacalcitol in psoriasis, and suggest that it may be efficacious in the treatment of other inflammatory skin diseases.
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PMID:Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice. 893 67

As part of environmental toxicology, it is important to assess both the carcinogenic potential of xenobiotics and their mode of action on target cells. Since dysregulation of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, is considered as an early and essential component in the process of multistage carcinogenesis, we have studied the mode of ODC induction in Syrian-hamster-embryo(SHE) cells stage-exposed to carcinogens and to non-carcinogens. One-stage (5 hr) treatment of SHE cells with 50 microM clofibrate (CLF), a non-genotoxic carcinogen, or with 0.4 microM benzo(a)pyrene (BaP), a genotoxic carcinogen, slightly decreased basal ODC activity. Using the 2-stage exposure, 1 hr to carcinogen, then replacement by TPA for 5 hr, the ODC activity was higher than that obtained with TPA alone. This ODC superinduction was not observed when SHE cells were similarly pre-treated with non-carcinogenic compounds. Several environmental chemicals, pesticides, solvents, oxidizers and drugs were investigated with this SHE cell model. With one-stage exposure, some xenobiotics decreased basal ODC activity, while for others ODC changes were not noticeable. With 2-stage exposure (chemical followed by TPA), all carcinogens amplified the TPA-inducing effect, resulting in ODC superinduction. Comparative studies of the action of carcinogens and of non-carcinogens, using 2-stage exposure protocols, clearly show a close relationship between ODC induction rate and morphological transformation frequency.
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PMID:Two-stage exposure of Syrian-hamster-embryo cells to environmental carcinogens: superinduction of ornithine decarboxylase correlates with increase of morphological-transformation frequency. 949 43

We have conducted a study to determine the carcinogenic potential of ethylene glycol monomethyl ether (EGME), a member of the glycol ether family, as compared to its reactive metabolite 2-methoxy-acetaldehyde (MALD). Since disruption of equilibrium between cell proliferation and cell death is thought to play a key role in multistage carcinogenesis, we investigated, in Syrian hamster embryo (SHE) cells exposed to various doses of EGME and MALD, impairment in apoptosis rate and in ornithine decarboxylase (ODC) metabolism. The activity of this rate-limiting enzyme of polyamine biosynthesis is closely related to cell proliferation and cell transformation. At the end-point, comparative action of the two products on SHE cell morphological transformation frequency was evaluated. One-stage exposure of SHE cells to 2 mM EGME and 200 microM MALD for 5 h did not change basal apoptotic level, whereas 0.16 microM phorbol ester (TPA) decreased it. Using two-stage exposure protocol (1 h xenobiotic followed by 5 h TPA), MALD strongly inhibited apoptosis more than did TPA alone; the parent compound EGME did not have any effect on TPA inhibiting action. Western blotting analysis showed that sequential treatment (MALD/TPA) increased Bcl-2 oncoprotein expression, whereas Bcl-XL and Bax proteins were not changed. The same staged exposure of SHE cells to MALD/TPA strongly induced ODC activity, and the rate was higher than that obtained with TPA alone: this was accompanied by an increase of ODC protein level. This ODC superinduction was not observed with EGME/TPA treatment. In long-term SHE-cell morphological transformation assay, staged exposure to MALD (800 microM or 1 mM for 24 h) followed by TPA applications increased the number of transformed colonies at the seventh day. Such early cooperative events as apoptosis inhibition and ODC superinduction, followed by the increase of SHE-cell transformation frequency, are highly indicative of a carcinogenic potential for the metabolite, MALD.
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PMID:Apoptosis inhibition and ornithine decarboxylase superinduction as early epigenetic events in morphological transformation of Syrian hamster embryo cells exposed to 2-methoxyacetaldehyde, a metabolite of 2-methoxyethanol. 1022 Dec 78

Recent studies clearly demonstrate that several environmental carcinogens lack the ability to initially induce genetic damage. In that view, multistage chemical carcinogenesis may be processed under the control of a variety of epigenetic events in addition to genotoxic impacts. The understanding of this mechanism as reviewed in this report requires knowledge of early changes induced by carcinogens in target cells, biochemical, biological and molecular reactions closely related to both sides of the growth equation: cell proliferation and programmed death. Among several cell transformation models, the most suitable for carcinogen detection and mechanistic study is the Syrian hamster embryo (SHE) cell transformation assay. This closely mimics the multistage carcinogenesis and we can examine, in a relatively short time (8 days), the mechanisms by which genotoxic and non-genotoxic agents may increase the frequency of cell transformation as a preneoplastic end-point. The mode of action of hundred of compounds, carcinogens and non-carcinogens, has been explored so far using one-stage and two-stage treatment protocols. In general, with the two-stage protocol, all carcinogens, irrespective of their genotoxic or non-genotoxic potential, give unambiguous positive results. Since perturbations of cell proliferation and death are considered essential events in the process of carcinogenesis, studies have been conducted on the dysregulation of two specific parameters, the induction of ornithine decarboxylase (ODC) an enzyme related to cell proliferation, and the apoptosis rate, when SHE cells are exposed to carcinogens. In one-stage treatment (5 h-24 h), only the promoter TPA induces ODC activity, while other carcinogens do not increase this activity. Using the two-stage exposure protocol (1 h xenobiotic/5 h TPA), all carcinogens both genotoxic and non-genotoxic, are able to stimulate ODC activity above the level obtained with TPA alone. Based on the two-stage treatment with carcinogens a close relationship can be obtained between the ODC superinduction and the increase of morphological cell transformation frequency. In cancer development, it is postulated that the inhibition of apoptosis may help altered cells to escape cell death and acquire a tumorigenic phenotype. Two-stage treatment carcinogen/TPA, effectively decreases the apoptotic rate. This is accompanied by an upregulation of the Bcl-2 oncoprotein, a well-known apoptotic inhibitor. However, treatment with a non-carcinogen phthalic anhydride, also inhibits apoptosis while it does not superinduce ODC activity. Although inhibition of apoptosis is not specific to the carcinogenic compound, both superinduction of ODC activity and inhibition of apoptosis via Bcl-2 upregulation may cooperate during the early stages of the carcinogenic process. In a long-term stage transformation assay, the rate of transformed colonies is relatively low (2-8%) bringing about the slow evolution of tumoral disease in humans and tumoral induction in rodents. This could be the consequence of the activation of various cellular repair mechanisms during the exposure time. Experimental data reported so far point out that genotoxic and non-genotoxic carcinogens, thought to be more active in the initiation or in the promotion stage, must share the same stage pathway leading to cancer development.
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PMID:Epigenetic events during the process of cell transformation induced by carcinogens (review). 1037 83

A transgenic mouse model was developed in which ornithine decarboxylase (ODC) can be overexpressed in a tissue-specific and regulated manner. Hair follicle keratinocytes were targeted by use of a bovine keratin 6 (K6) promoter/regulatory region, and regulation was accomplished by using the tetracycline-regulated transactivator/tetracycline-response element system. Double-transgenic mice carrying both transgenes (K6/tetracycline-regulatable transactivator protein (tTA) and tetracycline-response element/Odc) on a C57Bl/6 background had no obvious phenotypic abnormalities in the absence (Odc transgene-expressed) of doxycycline (a tetracycline analog) in the drinking water. However, induction of K6-driven tTA expression by the tumor promoter (12-O-tetradecanoylphorbol-13-acetate) (TPA) led to very high levels of epidermal ODC activity and robust hyperplasia, especially involving hair follicles. Both effects were abolished by inclusion of doxycycline in the drinking water to repress transgene expression. Finally, the number of papillomas that developed in a standard (7,12-dimethybenz[a]anthracene) (DMBA)/TPA protocol was greatly reduced in mice in which transgenic Odc expression was repressed by doxycycline. Our results demonstrated that the higher levels of ODC expression produced in the transgenic model in the induced versus the repressed condition make the normally promotion-resistant C57Bl/6 strain much more sensitive to the short-term and long-term (i.e., tumor-promoting) effects of TPA.
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PMID:Conversion of C57Bl/6 mice from a tumor promotion-resistant to a -sensitive phenotype by enhanced ornithine decarboxylase expression. 1048 19

In recent years, there have been considerable efforts to search for naturally occurring substances for intervention of carcinogenesis. Many components from medicinal or dietary plants have been identified to possess potential chemopreventive properties. For instance, curcumin, a yellow colouring agent from turmeric (Curcuma longa Linn., Zingiberaceae) has been shown to inhibit tumor formation in diverse animal models. Alpinia oxyphylla Miquel that also belongs to ginger family has been used in oriental herbal medicine. In the present work, we have evaluated the anti-tumor promoting potential of yakuchinone A (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenyl-3-heptanone) and yakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3-one), major pungent ingredients of A. oxyphylla. Thus, topical application of yakuchinone A or B significantly suppressed TPA-induced epidermal ornithine decarboxylase activity. They also reduced TPA-stimulated production of tumor necrosis factor-alpha in cultured human promyelocytic leukemia (HL-60) cells. Both compounds blunted the TPA-induced superoxide generation in differentiated HL-60 cells in a concentration-related manner and also inhibited lipid peroxidation in rat brain homogenates. Furthermore, yakuchinone A and yakuchinone B nullified the activation of the activator protein-1 (AP-1) in immortalized mouse fibroblast cells in culture. These findings indicate that pungent diarylheptanoids from A. oxyphylla have anti-tumor promotional properties that can contribute to their chemopreventive potential.
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PMID:Anti-tumor promoting potential of naturally occurring diarylheptanoids structurally related to curcumin. 1051 78

In the mouse study, topical application of green tea polyphenols (GTP) significantly inhibited TPA-induced increasing of epidermal ornithine decarboxylase (ODC) and increased the activities of several antioxidant enzymes (CAT, GR and GST). In another in vitro study, when GTP was incubated with TPA and mice polymorphonuclear leukocytes (PMNs), TPA induced hydrogen peroxide formation was markedly suppressed with a dose-dependent relationship. The results suggest that the antioxidative effect of GTP may play an important role in inhibiting tumor promotion.
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PMID:[The antioxidative mechanisms of tea polyphenols in inhibiting tumor promotion by TPA]. 1068 39


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