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)

Myocardial ornithine decarboxylase appears to have characteristics similar to those of enzymes isolated from other tissues. Ornithine decarboxylase activity decreased very rapidly after the death of the animal. Storage of the cell sap fraction at 0 degrees C or -15 degrees C, however, led to only a small decrease in the enzyme activity up to 3 days after preparation. Pyridoxal phosphate at an optimum of 50 muM was essential for full enzyme activity. Thiol compounds did not increase the myocardial ornithine decarboxylase enzyme activity. The subcellular distribution of the enzyme in the myocardium was found to be different from that reported in other tissues. A partial purification of the enzyme was possible using the proteins precipitated at pH 5 from a cell-soluble fraction or by passing a soluble fraction through a Sephadex G 100 gel column. ATP, ADP, and AMP inhibited ornithine decarboxylase at high concentrations (5 mM), but GTP, CTP, and ITP inhibited at a 1 mM concentration and above.
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PMID:Some properties of rat myocardial ornithine decarboxylase and the in vitro effects of nucleotides. 0 62

Difluoromethylornithine (DFMO) is an investigational chemopreventive agent that inhibits ornithine decarboxylase (ODC) activity, lowers cellular polyamine concentrations, and decreases cell proliferation in vivo and in vitro. In five subjects we have compared the polyamine concentrations in rectal mucosal biopsies and in exfoliated buccal mucosal cells (EBM) before and after DFMO treatment to assess the suitability of EBM as an easily accessible marker tissue for DFMO suppression of polyamine synthesis in the rectal mucosa. One month of 3 g/m2/day of DFMO treatment caused a statistically significant decrease in putrescine and spermidine concentrations in rectal mucosa biopsy specimens but not in EBM samples. ODC activity in EBM was high (approximately 1 mumol/min/mg protein), resistant to DFMO inhibition (Ki = 4200 microM), dependent on GTP concentration (maximal at 0.1 mM), and was reduced concomitantly with bacterial concentration by antiseptic mouthwashing. Bacteria adherent to EBM were visible by electron microscopy. Forty bacterial colonies/ng protein were culturable from washed EBM samples. Oral bacteria preclude the use of EBM samples as a marker tissue of DFMO effect in the rectal mucosa, but oral DFMO therapy is effective in depleting polyamines in rectal mucosa.
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PMID:Polyamine contents in rectal and buccal mucosae in humans treated with oral difluoromethylornithine. 130 95

Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582-3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1-24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy-eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30-46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects.
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PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea. 145 78

Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273-285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7-12, 1988; Carcinogenesis (Lond.), 10: 411-415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527-1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12-O-tetradecanoylphorbol-13-acetate (TPA) and other skin tumor promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin tumor promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, (-)epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-tumor-promoting effects against a wide spectrum of skin tumor promoters.
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PMID:Inhibition of skin tumor promoter-caused induction of epidermal ornithine decarboxylase in SENCAR mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives. 161 28

The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.
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PMID:Increased mucosal ornithine decarboxylase activity in human gastric cancer. 199 84

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10(-4) M/10(6) cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.
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PMID:[In vitro and in vivo effect of thyroid hormones on the growth of neuroblastoma cells. I. The effect of triiodothyronine in vitro]. 216 39

Casein kinase II and ornithine decarboxylase were purified from a virally-transformed macrophage-like cell line, RAW264. The addition of casein kinase II to a reaction mixture containing [tau-32P]GTP, Mg++, and ornithine decarboxylase led to the phosphorylation of a 55,000 dalton protein band in the purified preparation of ornithine decarboxylase. Stoichiometric estimates indicated that casein kinase II incorporated 0.15 mole of phosphate per mole of ornithine decarboxylase, which was increased to 0.3 mole/per mole in the presence of spermine. The apparent Km and Vmax values for the casein kinase II-mediated phosphorylation of ornithine decarboxylase were 0.36 microM and 62.5 nmol/min./mg kinase. The addition of spermine to the reaction did not alter the Km but increased the Vmax to 100 nmol/min./mg kinase. The phosphorylation of ornithine decarboxylase by casein kinase II affected neither the rate of maximal ornithine decarboxylase activity nor the affinity of the enzyme for ornithine.
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PMID:Phosphorylation of ornithine decarboxylase by casein kinase II from RAW264 cells. 222 53

Ornithine decarboxylase (ODC) activity was measured in colon adenocarcinomas and adjacent normal-appearing colon mucosa from a total of 40 patients undergoing surgical resections. The enzyme activity was measured in the presence and absence of GTP, since recent work has demonstrated a GTP-activatable form of ODC in some murine and human tumors. In general, ODC specific activity was higher in adenocarcinomas than in adjacent normal-appearing mucosa. Of greater interest, however, was the finding that 13 of 40 tumors and 3 of 40 mucosae contained a GTP-activatable form of ODC. These are minimal estimates of the proportion of tissues positive for this enzyme form, since a multiple sampling protocol indicated that expression of a GTP-activatable ODC was not uniform throughout a given tumor. Chromatographic analyses of tumor extracts revealed the presence in some tumors of multiple size forms of ODC, only some of which were activated by GTP. Enzyme kinetic data indicated that the multiple forms of ODC can have different affinities for L-ornithine and that GTP can "normalize" the aberrant kinetic properties of these forms. While there was no statistically significant correlation of the presence of a GTP-activatable ODC with stage of disease, analysis of our data revealed a positive association of a GTP-activatable ODC with tumor site; a much higher percentage of tumors of the cecum contained this ODC isoform than tumors of other colonic segments (64% versus less than or equal to 25% for other sites). These results demonstrate (a) the presence of a functionally distinct form of ODC in some human colon adenocarcinomas and (b) a distinct regional distribution of this ODC form within the colon. We suggest this alteration in a key enzyme in the growth-associated pathway of polyamine biosynthesis may play a role in colon tumor progression.
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PMID:Properties of ornithine decarboxylase in human colorectal adenocarcinomas. 231 97

In the early chick embryo, inhibition of polyamine synthesis by alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, blocks development at gastrulation. This effect was paralleled by a marked suppression of RNA and protein synthesis. There was no major change in cell cycle distribution in DFMO-treated embryos. Nevertheless, analysis of DNA synthesis and mitotic index indicated a prolongation of the cell cycle, possibly affecting all the phases. The inhibition of RNA synthesis in polyamine-depleted embryos, as evaluated by [3H]uridine incorporation, was not a result of reduced uptake or expansion of the UTP pool, and there was no deficiency or major imbalance among the ATP, GTP, and CTP pools. On the basis of agarose gel electrophoretic analyses of the various RNA species, and experiments using RNA synthesis inhibitors with different modes of action (actinomycin D, alpha-amanitin, and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), it was concluded that the DFMO-induced gastrular arrest was due to general inhibition of transcription.
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PMID:Transcriptional inhibition in early chick embryos as a result of polyamine depletion. 242 48

Casein kinase II from a virally-transformed macrophage cell line (RAW264) was purified by a sequential DEAE, Procion Red, phosvitin-Sepharose and heparin-Sepharose chromatography. With [tau-32P]GTP as a phosphate donor and casein as a substrate, the kinase was stimulated by polyamines and inhibited by heparin. The purified kinase had a specific activity of 1137 nmol/min/mg protein and exhibited three major protein bands of 40 K, 35 K, and 25 K. Under non-denaturing conditions in 50 mM Tris-50 mM NaCl the enzyme was eluted as a single peak with molecular weight of 110 K. Incubation of kinase in the presence of [tau-32P]GTP and Mg2+ resulted in phosphorylation of the 25 K protein band of the enzyme. In the presence of [tau-32P]GTP and Mg2+ the kinase was able to phosphorylate 55 K protein band in purified ornithine decarboxylase preparation from RAW264 cells and the rat-type II regulatory subunit of the cyclic AMP-dependent protein kinase.
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PMID:Characterization of casein kinase II from a virally transformed macrophage-like cell line, RAW264. 262 1


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