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)

Sequence analysis of the first 549 nucleotides (nt) of the non-translated 5' end of the cloned mouse ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17)-encoding sequence shows that this sequence is closely related to nt 1946-1395 of Moloney murine leukemia virus (MuLV). The viral sequence, however, is oriented anti-sense relative to the ODC sequence. This orientation makes it unlikely to be a cloning artifact mediated by reverse transcriptase, but rather a recombination between genomic DNA and a MuLV-like provirus. In the cell line, from which the cDNA clone originated, Katz and Kahana [EMBO J. 8 (1989) 1163-1167] have shown that an intragenic deletion and amplification of the ODC gene had taken place. We believe that an additional recombination also has occurred in this cell line. The cDNA clone studied was obtained after selecting for high ODC expression. It is conceivable that the retroviral sequence contains an intragenic enhancer which is also functional in the anti-sense orientation. The inserted sequence contains two repeats which share homology with known enhancer elements. The reported recombination event shows that caution is needed when selective pressure is applied for the isolation and characterization of genes.
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PMID:The long leader sequence of the mouse ornithine decarboxylase mRNA, previously suspected to be a cloning artifact, is probably a product of recombination with MuLV-like retrovirus. 176 76

In order to characterize the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and xenografts, their growth kinetic parameters and some biochemical characteristics concerning the receptor status and polyamine metabolism were determined and compared. The doubling times calculated from the growth curves showed higher proliferation rate of MDA-MB-231 cells, both in culture (21 hours) and in xenograft (9.7 days), in comparison to the MCF-7 cells which had values of 32 hours and 11.6 days, respectively. Growth-dependent changes observed in the intracellular putrescine, spermidine and spermine concentrations indicated a higher activity of polyamine metabolism in the MDA-MB-231 cells and xenograft as well. However, biosynthetic key-enzyme ornithine decarboxylase activity (ODC, EC 4.1.1.17) showed neither characteristic differences between the two types of breast cancer, nor consistent relationship with their proliferation rate. Metabolic alterations of the MCF-7 and MDA-MB-231 cell lines grown in vitro were also reflected in the polyamine composition of their culture medium. Independently of their receptor status, both types of breast cancer were responsive to difluoromethylornithine (DFMO) treatment. DFMO inhibited the ODC activity totally and depleted the cellular polyamine levels. MCF-7 cells in culture were more sensitive to the antitumoral effect of DFMO than the MDA-MB-231 line, while the rate of growth inhibition did not differ significantly in the xenografts. The present results provided further evidence on the different polyamine metabolism of ER-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells in vitro and in vivo, suggesting a correlation of hormonal modulation with polyamines as a determinant group of biological response modifiers.
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PMID:Comparative studies on the polyamine metabolism and DFMO treatment of MCF-7 and MDA-MB-231 breast cancer cell lines and xenografts. 176 53

Ornithine decarboxylase activity was determined during the development of the peripheral auditory system in the murine otocyst with the goal of understanding the role of this enzyme in the morphological and functional maturation of the inner ear. At gestational days 11 and 12 enzyme activity was more than 10-fold higher than adult levels. A sharp decline occurred between day 12 and 13 after which activity rose to a peak around day 15. Activity then dropped continuously until near-adult levels were reached at birth. A lower specific activity of ODC but a similar time-course was seen in otocysts explanted at gestational day 13 and subsequently cultured for 6 days. For two stages of development, enzyme activity and binding of 3H-alpha-difluoromethylornithine were compared. The four-fold difference in enzymatic activity on gestational days 15 and 17 was paralleled by a similar difference in binding. Ornithine decarboxylase activity during inner ear development therefore seems primarily regulated at the level of protein synthesis. Ornithine decarboxylase activity correlates with major inductive events in the morphogenesis of the cartilagenous otic capsule that serves as a template for the formation of the bony labyrinth. The pattern of activity may reflect the changes in the head mesenchyme that is recruited by the otocyst to aggregate and form its protective otic capsule.
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PMID:Ornithine decarboxylase activity during development of the mouse inner ear in vivo and in vitro. 178 95

Impairment of polyamine synthesis by treatment with difluoromehtylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to alter normal brain development. In the present study we determined the effect of DFMO treatment during a discrete developmental period on polyamine levels and on the in situ activity of calpain, as reflected by the level of degradation of spectrin, in various brain regions of rat pups. DFMO treatment from postnatal days 5 to 10 produced a marked decrease in putrescine levels in every brain structure and a significant decrease in spectrin breakdown levels in hippocampus and cortex but not in cerebellum. The results indicate that the ODC/polyamine pathway partly regulates the in situ activity of calpain and that polyamines may play a role in both growth and degeneration phenomena.
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PMID:Effect of treatment with difluoromethylornithine on polyamine and spectrin breakdown levels in neonatal rat brain. 179 May 96

The ability of the promotor/enhancer region of the mouse ornithine decarboxylase gene to respond to various stimuli was studied. This region was subcloned into multiple fragments and these were inserted in front of the chloramphenicol acetyltransferase gene on an expression vector, pBLCAT3. These ODC/CAT constructs were transfected into a mouse macrophage-like cell line, RAW264. The transfected cells were stimulated by bacterial lipopolysaccharide, 8-bromo cAMP or both followed by analysis of chloramphenicol acetyltransferase activity. Optimal inducible chloramphenicol acetyltransferase expression was obtained when sequences from -90 to +12 (with respect to the transcriptional start site) were tested in cells treated with a combination of lipopolysaccharide and 8-bromo cAMP. A putative cyclic AMP response element located at -48 was altered by site-directed mutagenesis but these alterations did not diminish activity in response to stimulation with lipopolysaccharide and 8-bromo cAMP.
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PMID:Regulation of mouse ornithine decarboxylase gene expression in a macrophage-like cell line: synergistic induction by bacterial lipopolysaccharide and cAMP. 184 9

The effects of dexamethasone on ornithine decarboxylase gene expression were examined in rat pancreatic AR42J cells. Dexamethasone increased ornithine decarboxylase activity and messenger RNA (mRNA) concentrations in a time-dependent manner, with a maximal effect at 12 hours (207% +/- 63% and 327% +/- 34% of control, respectively; n = 5). Ornithine decarboxylase mRNA levels returned to control values at 48 hours, whereas ornithine decarboxylase activity was decreased to 41% +/- 8% of control (n = 3). Dexamethasone induction of ornithine decarboxylase mRNA was dose dependent, with half-maximal effects at 10(-8) mol/L (210% +/- 20% of control; n = 4) and maximal effects at 10(-7) mol/L (327% +/- 26% of control; n = 4). The glucocorticoid antagonist RU 38486 blocked the dexamethasone effects in a dose-dependent manner, with maximal effects occurring at 10(-7) mol/L (120% +/- 18% of control; n = 3). When protein synthesis was blocked by addition of cycloheximide, ornithine decarboxylase mRNA levels remained unchanged in response to glucocorticoids, indicating a primary effect of dexamethasone. Furthermore, cycloheximide by itself had no significant effect on ornithine decarboxylase mRNA levels. Inhibition of transcription with actinomycin D showed a half-life for ornithine decarboxylase mRNA of approximately 240 minutes. Ornithine decarboxylase mRNA stability was not affected by dexamethasone pretreatment for 12 hours. Therefore, these data suggest that dexamethasone regulates ODC gene expression via glucocorticoid receptor-mediated gene transcription. Furthermore, translational mechanisms seem to be involved in glucocorticoid-regulated ornithine decarboxylase induction.
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PMID:Glucocorticoids stimulate ornithine decarboxylase gene expression in pancreatic AR42J cells. 188 4

The effects of a single ethanol administration on ornithine decarboxylase induction, polyamine metabolism and DNA synthesis in rat liver after partial hepatectomy were studied. Ethanol given 1 hr before partial hepatectomy at the dose of 2, 3 or 5 gm/kg body wt inhibited the increase in ornithine decarboxylase activity and that in the putrescine level in the liver 4 hr after partial hepatectomy. The hepatectomy increased the amount of ornithine decarboxylase messenger RNA expressed, and this amount was unaffected by ethanol administration. Further, ethanol did not accelerate the degradation of ornithine decarboxylase 4 hr after partial hepatectomy, indicating that the inhibition of ornithine decarboxylase activity caused by ethanol was not caused by a decrease in the ornithine decarboxylase messenger RNA level or by the acceleration of ODC degradation. The single dose of ethanol inhibited [3H]thymidine incorporation into the hepatic DNA 24 hr after partial hepatectomy. The suppression of [3H]thymidine incorporation was partially reversed by the administration of putrescine. These results suggested that ethanol inhibits the increase in ornithine decarboxylase activity after transcription, suppressing the accumulation of putrescine, which prevents DNA synthesis in response to hepatectomy.
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PMID:Effects of single ethanol administration on hepatic ornithine decarboxylase induction and polyamine metabolism. 191 73

Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats. Since alterations in gene expression may play a critical role in multistage hepatocarcinogenesis, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor (EGF) receptor and ODC (ornithine decarboxylase) genes, as well as endogenous retrovirus-like sequences, in F344 rat liver during the first 8 weeks of feeding a 0.16% Br931 diet and in liver tumours induced by chronic feeding of this diet. Northern blot analysis of poly A + liver RNA samples showed an increase in the level of RNAs homologous to rat leukaemia virus (RaLV) but no significant change in the level of 30S-retrovirus related RNAs in the liver RNA samples obtained from rats during the first 8 weeks of feeding the diet containing BR931. An increase in the levels of c-myc, c-H-ras and ODC transcripts was also seen in the liver RNA samples from the treated rats. Of particular interest was a decrease in the abundance of EGF receptor transcripts in the liver RNA samples from rats fed the BR931 diet. Increased levels of RaLV, c-myc, and ODC RNAs were also seen in the tumours induced by BR931, but this was not the case for 30S and c-H-ras. The liver tumour samples also showed a decrease in EGF receptor RNA. These changes in cellular levels of specific RNAs resemble, in several respect, those we previously described in rodent liver during regeneration and tumour promotion, and also those seen in rodent hepatomas induced by other agents. Therefore, they may reflect a common profile of gene expression relevant to liver proliferation and carcinogenesis.
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PMID:Changes in expression of cellular oncogenes and endogenous retrovirus-like sequences during hepatocarcinogenesis induced by a peroxisome proliferator. 193

Ornithine decarboxylase (ODC, EC 4.1.1.17) expression is subject to negative feedback regulation by the polyamines. The results of previous studies favor either translational or post-translational regulation. To facilitate further analysis of the mechanism by which polyamines affect ODC expression we have used a cell line (L1210-DFMOr) that overproduces ODC. This cell line was isolated by selection for resistance to the antiproliferative effect of the ODC inhibitor alpha-difluoromethylornithine (DFMO). These cells respond similarly to polyamine depletion and repletion as do their wild-type counterparts. When L1210-DFMOr cells were grown in the presence of 20 mM DFMO (i.e., when their polyamine content was reduced to an extent that still permitted a normal growth rate) ODC represented 4-5% of the soluble protein synthesized. After transfer of the cells to a medium lacking DFMO (i.e., when their polyamine pools were repleted), the rate of incorporation of [35S]methionine into ODC was one order of magnitude lower. Since this difference in incorporation of radioactivity into ODC remained the same irrespective of the pulse-label time used (between 2 and 20 min) it is likely to represent a true difference in ODC synthesis rate. Consequently, the pulse-label experiments cannot be explained by rapid degradation of the enzyme during the labeling period. The difference in ODC synthesis rate was not accompanied by a corresponding difference in the steady-state level of ODC mRNA. Analyses of the distribution of ODC mRNA in polysome profiles did not demonstrate any major difference between cells grown in the absence or presence of DFMO, even though the ODC synthesis rate differed by as much as 10-fold. However, the distribution of the ODC mRNA in the polysome profiles indicated that the message was poorly translated. Thus, most of the ODC mRNA was present in fractions containing ribosomal subunits or monosomes. Inhibition of elongation by cycloheximide treatment resulted in a shift of the ODC mRNA from the region of the gradient containing ribosomal subunits to that containing mono- and polysomes, indicating that most of the ODC mRNA was accessible to translation. Taken together these data lend support to a translational control mechanism which involves both initiation and elongation.
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PMID:On the translational control of ornithine decarboxylase expression by polyamines. 193 10

Although the precise intracellular function(s) of the polyamines remain incompletely defined, a myraid of evidence now shows that the polyamines must accumulate or be maintained at a specific intracellular concentration in order for all mammalian cells to grow or divide. The initial step in polyamine biosynthesis normally involves the decarboxylation of ornithine by the enzyme ornithine decarboxylase (ODCase E.C. 4.1.1.17) to yield putrescine. Increases in the steady-state level of intracellular ornithine have been reported to markedly alter the accumulation of the polyamines following stimulation of Reuber H35 Hepatoma cells with 12-O-tetradecanoylphorbol-beta-acetate (TPA) in the presence of serum (Wu and Byus: (Biochem. Biophys. Acta 804:89-99, 1984); Wu et al.: (Cancer Res. 41:3384-3391, 1981). We wished to determine whether or not incubation of H35 hepatoma cells with exogenous ornithine would result in a stimulation of DNA synthesis following treatment with the mitogens TPA and insulin. For these studies, H35 cells were maintained under serum-free conditions for 2-3 days in order to obtain synchronous cultures suitable for analysis of the level of DNA synthesis. Cultures treated in this manner were highly viable, maintained similar growth rates, and possessed the equivalent levels of intracellular ornithine and polyamines as the serum-containing cultures. Arginine levels, however, were approximately twofold higher following culture under serum-restricted conditions for 3 days. The addition of exogenous ornithine (0.5 mM) was accompanied by a 4-5-fold increase in intracellular steady-state ornithine levels and by a 6-8-fold increase in the presence of TPA and ornithine. In a manner identical to the serum-containing cultures (Wu and Byus (1984] the addition of TPA and exogenous ornithine to the serum-free cells caused a dose-dependent increase in intracellular putrescine (up to 5-fold) and a concomitant decrease in ODC activity in comparison to stimulation with TPA alone. The addition of TPA led to a 3-5-fold increase in the incorporation of tritiated thymidine into DNA. In the presence of exogenous ornithine, TPA-induced DNA synthesis was further stimulated more than twofold in a dose-dependent manner. Insulin (10(-10)-10(-8) M) proved to be more efficacious as a mitogen in the H35 cells and led to greater stimulation of DNA synthesis than TPA. Insulin alone also resulted in a higher steady-state level of ornithine and putrescine in comparison with TPA alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The level of substrate ornithine can alter polyamine-dependent DNA synthesis following phorbolester stimulation of cultured hepatoma cells. 193 49


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