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)

Teleocidin (5 micrograms/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 mumol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 mumol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 mumol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 mumol/mouse), nordihydroguaiaretic acid (NDGA) (30 mumol/mouse), quercetin (10 mumol/mouse), and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 mumol/mouse) and quercetin (10 mumol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.
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PMID:Inhibition of teleocidin-caused epidermal ornithine decarboxylase induction by phospholipase A2-, cyclooxygenase- and lipoxygenase-inhibitors. 392 44

Application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 20 nmol/mouse), a tumor-promoting agent, to mouse skin results in an induction of epidermal ornithine decarboxylase (ODC; EC 4.1.1.17). Induction of ODC by TPA was inhibited by treatment of skin with indomethacin (1.12 mumol/mouse), a cyclooxygenase inhibitor, and the ODC activity suppressed by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse) as described first by Verma et al. (Cancer Res., 40: 308-315, 1980). Treatment of mice with tetracaine (20 and 100 mumol/mouse), a nonspecific phospholipase A2 inhibitor, inhibited the induction of ODC by TPA. More specific phospholipase A2 inhibitors, mepacrine (20 mumol/mouse) and p-bromophenacyl bromide (10 mumol/mouse), also inhibited the ODC induction. The TPA-induced ODC inhibited by mepacrine was not restored by the treatment of mice with PGE2. TPA-induced ODC inhibited by either mepacrine or p-bromophenacyl bromide was partially but significantly restored by treatment with arachidonic acid (1 to 40 mumol/mouse). Neither PGE2 nor arachidonic acid alone could induce the epidermal ODC. Treatment of mice with nordihydroguaiaretic acid (10 to 90 mumol/mouse), a lipoxygenase inhibitor, also inhibited the induction of ODC by TPA. These results strongly indicate that the stimulation of phospholipase A2 activity is a crucial process in inducing mouse epidermal ODC by TPA and not only cyclooxygenase product (i.e., PGE2) but also lipoxygenase product(s) are involved in the mechanism of ODC induction. Our present data also suggest that the above arachidonate metabolites are essential but not sufficient factors for the TPA-stimulated induction of ODC.
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PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by phospholipase A2 inhibitors and lipoxygenase inhibitor. 680 48

Induction of epidermal ornithine decarboxylase (ODC) by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, was inhibited by treatment of mouse skin with phenidone (3-90 mumol/mouse), nordihydroguaiaretic acid (30 mumol/mouse) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C, 30 mumol/mouse), which are well-known lipoxygenase inhibitors. Phenidone and BW 755C are also to be cyclooxygenase inhibitors. Inhibition of TPA-induced ODC by indomethacin (1.12 mumol/mouse), a selective cyclooxygenase inhibitor, was counteracted by prostaglandin E2 (PGE2) (140 nmol/mouse). This counteracting effect of PGE2 was reversed by the treatment of mice with nordihydroguaiaretic acid (30 mumol/mouse) or phenidone (30 mumol/mouse). ODC activity which was suppressed by nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse was not further inhibited by indomethacin (1.12 mumol/mouse). In addition, the counteracting action of PGE2 (140 nmol/mouse) was not observed in mice treated with nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse. Thus, the suppressive effect of nordihydroguaiaretic acid or phenidone on the ODC induction by TPA would be due to the inhibition of lipoxygenase. The above findings strongly suggest that not only cyclooxygenase product (i.e., PGE2) but also lipoxygenase product(s) are involved in the mechanism of ODC induction in mouse epidermis, and a lack of either cyclooxygenase product or lipoxygenase product(s) causes a failure of ODC induction by TPA.
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PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by lipoxygenase inhibitors: possible role of product(s) of lipoxygenase pathway. 681 41

The biochemical effects of the non-12-0-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter thapsigargin (TG), which does not bind to the phorbol-ester receptor, or activate protein kinase C (PKC) or increase inositol polyphosphates, were characterized in mouse epidermis in vivo. The cold scraping method is required to detect the induction of ornithine decarboxylase (ODC) activity by TG, a response much smaller than that caused by TPA and with a different time course. TG pre-treatments do not alter or cause a refractory state against ODC induction by TPA. But TG stimulates hydroperoxide (HPx) production and RNA, protein, and DNA synthesis almost as much as TPA. Moreover, the sequential effects of TG and TPA on DNA synthesis are identical: early inhibition at 8 hr followed by maximal stimulation at 16-32 hr. TG-stimulated HPx production requires protein synthesis and xanthine oxidase, phospholipase A2, and lipoxygenase activities but not RNA and DNA synthesis, and cyclooxygenase and protease activities. The HPx response to TG is not mimicked by the PKC activator prostratin or inhibited by pre-treatments with prostratin or specific PKC inhibitors. However, the Ca(2+)-ATPase inhibitor cyclopiazonic acid and the Ca2+ ionophore and weak ODC inducer A23187 mimic remarkably the HPx responses to TG and TPA. Since TG and A23187 are known to be, respectively, weak and incomplete tumor promoters as compared with TPA, the present results suggest that the HPx responses common to Ca(2+)-mobilizing and TPA- or non-TPA-type agents are insufficient to achieve tumor promotion in the absence of major ODC induction.
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PMID:Ability of the non-phorbol ester-type tumor-promoter thapsigargin to mimic the stimulatory effects of 12-0-tetradecanoylphorbol-13-acetate on ornithine decarboxylase activity, hydroperoxide production, and macromolecule synthesis in mouse epidermis in vivo. 825 22

In prior studies we and others have shown that oral feeding of a polyphenolic fraction isolated from green tea (GTP) or water extract of green tea affords protection against ultraviolet B (UVB) radiation-induced carcinogenesis in SKH-1 hairless mice (Wang et al., Carcinogenesis 12, 1527-1530, 1991). It is known that exposure of murine skin to UVB radiation results in cutaneous edema, depletion of the antioxidant-defense system and induction of ornithine decarboxylase (ODC) and cyclooxygenase activities. In this study we assessed the protective effect of GTP on these UVB radiation-caused changes in murine skin. Oral feeding of 0.2% GTP (wt/vol) as the sole source of drinking water for 30 days to SKH-1 hairless mice followed by irradiation with UVB (900 mJ/cm2) resulted in significant protection against UVB radiation-caused cutaneous edema (P < 0.0005) and depletion of the antioxidant-defense system in epidermis (P < 0.01-0.02). The oral feeding of GTP also resulted in significant protection against UVB radiation-caused induction of epidermal ODC (P < 0.005-0.01) and cyclooxygenase activities (P < 0.0001) in a time-dependent manner. Our data indicate that the inhibition of UVB radiation-caused changes in these markers of tumor promotion in murine skin by GTP may be one of the possible mechanisms of chemopreventive effects associated with green tea against UVB-induced tumorigenesis. The results of this study suggest that green tea, specifically polyphenols present therein, may be useful against inflammatory responses associated with the exposure of skin to solar radiation.
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PMID:Protection against ultraviolet B radiation-induced effects in the skin of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea. 828 25

Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.
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PMID:Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. 836 13

Previous studies demonstrated that epidermal growth factor (EGF) and polyamines (PA) are capable of protecting gastric mucosa against topical irritants. This study was designed to examine whether EGF, PA, and PG affect the healing of acute gastric lesions induced by water immersion and restraint stress. It was found that the healing process of stress lesions in sham-operated rats was significant after 6 hr after stress, and after 24 hr the number of stress lesions was reduced by about 75%. In sham-operated rats, the healing of ulcerations observed at 6, 12, and 24 hr after the stress was accompanied by gradual restoration of DNA synthesis, and both these processes were significantly reduced by administration of DFMO (an inhibitor of ornithine decarboxylase activity) or indomethacin (an inhibitor of cyclooxygenase). In salivectomized rats, the healing was significantly delayed and the DNA was lowered at all time intervals after the stress. Administration of EGF, spermine, aminoguanidine (an inhibitor of degradation of PA), or 16,16-dmPGE2 after stress promoted significantly the healing and DNA synthesis, but pretreatment with DFMO abolished the effect of EGF but not that of spermine. We conclude that EGF, PA, and PG are implicated in healing of stress lesions and that EGF acts, at least in part, by the stimulation of PA formation in the gastric mucosa.
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PMID:Epidermal growth factor, polyamines, and prostaglandins in healing of stress-induced gastric lesions in rats. 842 39

Role of prostaglandins on feeding-associated induction of ornithine decarboxylase in small intestine was studied. Rats received intraperitoneal injection of either saline, or 16,16-dimethyl prostaglandin E2, or TRY-200 (a stable prostaglandin I2 analog), or refeeding, after a 44 hr-fast. Four hours later, mucosae from duodenum, jejunum, and ileum were scraped for subsequent measurements of enzyme activity of ornithine decarboxylase by a radiometric technique. Refeeding resulted in a profound induction of enzyme activity throughout the small intestine. Parenteral administration of prostaglandin I2 also led to a significant induction with the level similar to refeeding. The stimulatory effect of prostaglandin I2 was completely abolished by a specific and irreversible enzyme inhibitor, difluoromethylornithine. Prostaglandin E2 had a similar but lesser effect than prostaglandin I2 on the induction of the enzyme activity. Pretreatment with indomethacin, a cyclooxygenase inhibitor had no effect on feeding-associated enzyme induction. These results indicate that although exogenous prostaglandin I2 appears to be a potent stimulant for ornithine decarboxylase activity in rat small intestine, endogenous prostaglandins seem to play little or no role in feeding-associated induction of ornithine decarboxylase.
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PMID:Effects of prostaglandins on ornithine decarboxylase activity in rat small intestine. 850 4

We have characterised the induction of the mitogen-inducible form of cyclooxygenase, COX-2, in the rat cerebral cortex in response to excitotoxin injection into the nucleus basalis. This model is associated with intense stimulation of the ascending pathway to the cerebral cortex, seizure activity, and subsequent ipsilateral cortical induction of various immediate early genes (IEGs), including c-fos, c-jun, and zif268, and ornithine decarboxylase enzyme activity and mRNA, all of which processes are sensitive to treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. In this study we show that excitotoxin injection also causes a marked induction of COX-2 mRNA in ipsilateral cortex detectable at 1 h and peaking at 4 h, where COX-2 mRNA levels were 19 times those in unoperated animals. Levels of COX-2 mRNA remained significantly elevated at 24 h. The early induction of COX-2 at 1 h was also seen in sham-operated animals, but at 4 h the COX-2 mRNA level was significantly increased (4.4-fold) in animals injected with excitotoxin compared with sham-operated animals. The induction at this time point (4 h) was explored pharmacologically and found to be significantly attenuated by treatment with MK-801 (1.5 mg/kg), lamotrigine (10 mg/kg), which prevents presynaptic glutamate release by blocking voltage-sensitive Na+ channels, and the glucocorticoid dexamethasone (3 mg/kg), which has an indirect inhibitory effect on phospholipase A2 and COX activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to synaptic excitation. 852 90

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


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