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)

Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC gene, demonstrated by nuclear run-on analysis, can account for the accumulation of ODC mRNAs. The involvement of catecholamines in these processes is demonstrated by using prazosin and propranolol, specific antagonists of alpha 1 and beta adrenoceptors, respectively. Prazosin reduces almost completely the rise of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity and mRNAs increase, however, over the values observed in regenerating liver of prazosin-untreated animals. These findings suggest that alpha 1-receptor activation triggers positive control signals for ODC gene expression at the early time of liver regeneration and, on the contrary, negative signals at later times by mainly post-transcriptional and transcriptional mechanisms, respectively. Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These results indicate that activation of both alpha 1- and beta-adrenoceptors causes the large increase in ODC activity. Pharmacological manipulation of intracellular Ca2+ levels by verapamil, a Ca2(+)-channel blocker, or neomycin, an inhibitor of Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC activity and mRNA accumulation at the times studied. As a working hypothesis it is proposed that Ca2(+)-mediated processes induced by catecholamines are involved in ODC gene expression during the prereplicative phase of liver regeneration.
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PMID:Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver. 197 90

Butylated hydroxyanisole (BHA) is a phenolic antioxidant that has been found to suppress the activity of skin tumor promoters. In this study, we investigated the effect of BHA on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion) and its gene expression induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse skin. TPA-induced ODC activity was markedly inhibited by the topical application of 55 mumol of BHA (the inhibition rate at 6 h was about 80%). In Northern and dot-blot analysis, the TPA-induced increase in ODC mRNA was shown to be markedly reduced by the same dose of BHA (the inhibition rate at 4 h was about 60%). These results suggest the involvement of a decrease in ODC gene expression in the mechanism of the inhibition of ODC activity by BHA.
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PMID:Effects of butylated hydroxyanisole on ornithine decarboxylase activity and its gene expression induced by phorbol ester tumor promoter. 199 91

The bacterial alkaline phosphatase (phoA) promoter and signal peptide have been used previously to control recombinant expression and secretion of eukaryotic proteins in Escherichia coli. Other reports have shown that this expression system can generate relatively modest levels of active hypoxanthine/guanine phosphoribosyltransferase (HPRT; hypoxanthine phosphoribosyltransferase; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), which carries part of the signal peptide but remains in the cytosol of the bacteria. Herein, the phoA promoter without its associated signal peptide is used to regulate expression of the HPRT of Schistosoma mansoni and the ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17) of Trypanosoma brucei, two enzymes that have been identified as potential targets for antiparasitic chemotherapy. The levels of recombinant expression range from 20% to 60% of the total bacterial protein, and the majority of both recombinant enzymes was soluble. The specific activity for the recombinant trypanosomal ODC was one-third to two-thirds that of the authentic native enzyme and yields were predicted to be 15-30 mg of active enzyme per liter of bacterial culture. The specific activity for the recombinant schistosomal HPRT was equivalent to that for the native enzyme purified from schistosomes and up to 10 mg of enzymatically active HPRT has been purified from a 0.5-liter culture of treated bacteria. These results represent a break-through in recombinant expression of HPRT and ODC.
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PMID:High level expression in Escherichia coli of soluble, enzymatically active schistosomal hypoxanthine/guanine phosphoribosyltransferase and trypanosomal ornithine decarboxylase. 200 85

The enzyme ornithine decarboxylase (ODC, EC 4.1.1.17) is believed to play an essential role in the growth and differentiation of cells by regulating the biosynthesis of polyamines. The 5' untranslated region (5' UTR) of the ODC mRNA of different species is rather unusual in length and GC content, and may therefore be involved in translational control of ODC protein synthesis. We cloned the rat ODC cDNA downstream of the phage T7 promoter in order to perform transcription/translation studies in vitro. Our results show that the intact 5' UTR of rat ODC mRNA, which is 303 nt in length, is a potent inhibitor of translation. Efficient synthesis in vitro of ODC protein is obtained when either 172 nt from the 5'-end or 236 nt from the 3'-end of the 5' UTR are removed. A truncated 5' UTR with a calculated free energy of less than -272 kJ (-65 kcal/mol) is unable to support the synthesis in vitro of ODC protein. The short open reading frame (ORF) present in the 5' UTR of rat ODC mRNA does not contribute to the observed inhibitory effect on translation efficiency in vitro. At low polyamine concentration the efficiency of translation in vitro of intact ODC mRNA is not relatively increased compared with that of an ODC mRNA having a truncated 5' UTR or with that of control globin mRNA. From this we conclude that the well-documented negative feedback control of intracellular polyamines on ODC expression is not regulated by effects of polyamines on the secondary structure of the 5' UTR of ODC mRNA.
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PMID:The translation in vitro of rat ornithine decarboxylase mRNA is blocked by its 5' untranslated region in a polyamine-independent way. 200 16

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates a rapid increase in ornithine decarboxylase (EC 4.1.1.17; ODC) activity in target cells. Here we demonstrate that this process involves a rapid accumulation of ODC mRNA, which is maximal 3 h after treatment (three- to eightfold greater than control cells) and decays to control levels within 18 h. Stimulation of ODC mRNA by TPA is blocked by phorbol dibutyrate down-regulation of protein kinase C (PKC). ODC mRNA was also induced by the PKC activators, phospholipase C and 1-oleoyl-2-acetyl-rac-glycerol, and blocked by kinase inhibitors (trifluoroperazine, H7, and palmitoyl-L-carnitine), consistent with a requirement for PKC activation in the induction mechanism. However, the non-PKC-specific protein kinase inhibitor HA1004 also suppressed expression of ODC mRNA in response to TPA, under conditions where it did not inhibit PKC, suggesting that additional kinases may be involved in the intracellular signalling process. The stability of the ODC mRNA (control value = 6.2 +/- 1.6 h) is not significantly changed by either TPA (5.7 +/- 0.8 h) or by cycloheximide (6.0 h). These results are inconsistent with any contribution from altered mRNA half-life towards the accumulation of ODC mRNA following treatment with phorbol ester tumor promoters.
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PMID:Involvement of protein kinase C in the regulation of ornithine decarboxylase mRNA by phorbol esters in rat hepatoma cells. 201 52

Ornithine decarboxylase (ODC; EC 4.1.1.17) could be induced in primary cultured hepatocytes of the frog, Xenopus laevis, by a hypotonic treatment. Addition of 10 mM putrescine caused a rapid decay of preinduced ODC after a lag period of 30 min. The putrescine-induced ODC decay was faster than the ODC decay in the presence of cycloheximide. Simultaneous addition of cycloheximide blocked the putrescine-induced acceleration of ODC decay, indicating an involvement of protein synthesis. Addition of putrescine to normal medium caused complete loss of ODC activity in 2 h and then ODC-inhibitory activity appeared and progressively increased. The inhibitory factor was non-dialysable and temperature-sensitive and showed a time-independent and stoichiometric pattern of ODC inhibition. On the basis of these observations the inhibitory factor was identified as ODC antizyme. These results indicated that in frog hepatocytes, like in mammalian cells and tissues, ODC is under negative feedback regulation mediated by antizyme.
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PMID:Presence of ornithine decarboxylase antizyme in primary cultured hepatocytes of the frog Xenopus laevis. 201 82

Growth of rats fed with a synthetic diet was studied under control conditions (arginine-rich), arginine starvation, and arginine starvation/refeeding. Hepatic polyamine concentrations and ornithine decarboxylase (ODC-)activity were determined for each population. In the livers of arginine-starved rats putrescine was decreased to half the control content within 8 days; upon refeeding, it returned to control levels within another 8 days. Spermidine content in liver tissue of arginine-starved rats remained rather stable for 7 days, but thereafter dropped to half the original value within two days. Refeeding for a period of 11 days was not enough to restore the spermidine content. The effects of arginine starvation/refeeding on spermine were very similar to those of spermidine. ODC specific activity, when correlated with growth, was higher in livers of arginine-starved rats than in control animals. Refeeding caused a decrease in ODC-activity although growth arrest was completely released. This apparent uncoupling of growth and ODC stimulation supports the theory that ODC in rat liver is regulated at three levels: first the growth-related component which is observed after stimulation by growth-hormone; second the known feed back control by polyamines, e.g. via antizyme; third the regulation at the level of the substrate supply which has been shown in this work. This is not a unique finding since very similar results have been obtained in previous experiments with the protozoan Tetrahymena thermophila. A remarkable observation of these assays was that L-ornithine, when added to the arginine-free diet was not able to substitute for L-arginine in directing growth and growth related processes.
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PMID:Polyamine biosynthesis in arginine-starved and refed rats. 203 2

The total cellular mass of the small intestine is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal growth. The polyamines (putrescine, spermidine and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase. ODC) are critical for many cell growth processes and appear to play important roles in intestinal growth. During intestinal adaptation in response to jejunectomy, lactation. pancreatic-biliary diversion, starvation-refeeding and feeding with kidney bean lectin, intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increase in ODC and polyamines is inhibited and intestinal growth is suppressed. In addition, the oral administration of exogenous polyamines results in precocious maturation of the neonatal rat intestine. These results suggest that the polyamines are important for intestinal growth.
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PMID:Polyamines in intestinal growth. 208 16

Rapid, polyamine-induced degradation of mammalian ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) (ODC) is though to be controlled by the availability of a small, ODC-binding protein termed antizyme. In this study we have investigated the ability of antizyme to bind ODC protein in various altered physiological states. In particular, cold, NaCl, spermidine and deprivation of coenzyme and substrate enhance enzyme-antizyme complex formation and are all found to promote ODC homodimer dissociation. Conversely, conditions that maintain the active ODC homodimer state prevent antizyme binding and inactivation of ODC. Further, covalent modification of ODC near its active site by difluoromethylornithine or phosphate also increases its sensitivity to antizyme. These results suggest that the initial signal in ODC degradation may actually be a subtle conformational change in the enzyme that enables antizyme to bind to the enzyme and may subsequently facilitate its degradation.
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PMID:Conformational changes in ornithine decarboxylase enable recognition by antizyme. 210 55

The effects of combined administration of tetragastrin and the ornithine decarboxylase inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the BUdR labelling indices of the fundic and antral mucosae, were investigated in inbred Wistar rats. Rats were given drinking water containing 2.5 g/l of DAP ad libitum and received alternate-day injections of 1 mg/kg body weight of tetragastrin in depot form after 25 weeks of oral treatment with MNNG. At week 52, prolonged administration of tetragastrin alone resulted in a significant reduction in the incidence and number of gastric cancers and a significant increase or decrease in the labelling indices of the fundic and antral mucosae, respectively. Concomitant administration of tetragastrin and DAP had no effect on the inhibition by tetragastrin of gastric carcinogenesis. With this treatment, the labelling index was significantly reduced in the fundic mucosa but not in the antral mucosa. These results suggest that ODC inhibitor does not attenuate tetragastrin inhibition of gastric carcinogenesis, and that anti-trophic action of tetragastrin on antral mucosa may be related to tetragastrin inhibition of gastric carcinogenesis.
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PMID:Effect of ornithine decarboxylase inhibitor on tetragastrin treatment of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 210 11


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