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

---

Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.
...
PMID:Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. 253 26

Induction of ornithine decarboxylase (ODC, E.C. 4.1.1.17) activity by parathyroid hormone (PTH) in cultured fetal rat osteoblasts was studied. PTH induced ODC activity and stimulated cAMP production in a dose-dependent manner, the ED50 for cAMP being five times as high as that for ODC. Induction of ODC activity by PTH was partly inhibited by actinomycin D and cycloheximide, with 40 and 55% inhibition, respectively. PTH increased the intracellular ionized calcium concentration ([Ca2+]i), which was absent in a Ca2+-free medium. Blocking calcium influx, lowering the extracellular calcium concentration, and adding trifluoperazine inhibited both induction of ODC activity and stimulation of cAMP production by PTH. A23187 (100 nM and 1 microM), combined with a low dose of PTH (4 nM), resulted in a synergistic induction of ODC activity and an inhibition of cAMP production. A23187 inhibited induction of ODC activity as well as stimulation of cAMP production by the dose of PTH (20 nM) maximally effective in inducing ODC activity. Forskolin together with this maximal dose of PTH resulted in an additive effect on ODC activity and a synergistic stimulation of cAMP production. The current results show similarities and differences with respect to results obtained with osteoblasts from other species and osteoblast cell lines. The present data indicate that (1) PTH stimulates ODC activity and this is partly due to new enzyme synthesis; (2) calcium is involved in induction of ODC activity and stimulation of cAMP production by PTH; furthermore, it is suggestive that calmodulin and/or protein kinase C are involved; and (3) stimulation of cAMP production by PTH depends on an optimal intracellular calcium concentration range.
...
PMID:Parathyroid hormone-induced ornithine decarboxylase activity in fetal rat osteoblasts. 255 85

Ornithine decarboxylase (ODC, EC 4.1.1.17) activity is induced in the RAW264 macrophage-like cell line by bacterial lipopolysaccharide (LPS). As little as 0.1 ng/ml LPS promoted an increase in ODC activity, while maximal ODC activity (30-fold above control) was induced with 1.0 microgram/ml LPS. An increase in ODC activity was detectable within 90 min of LPS addition. The LPS-induced increase in ODC activity was prevented by inhibitors of protein and RNA synthesis. The induction of the enzyme by LPS was not dependent on prostaglandin production. However, PGE2 (1 microgram/ml) and 8-bromo-cyclic AMP (1 mM), neither of which had an effect on ODC activity when added alone, each acted synergistically to enhance the LPS induction of ODC activity. Enzyme induction was not associated with an alteration in Km for ornithine, which remained constant at 0.04 mM. The extent of the increase in ODC in response to LPS increased with increasing cellular density. This relationship was dependent not on absolute cell density of the monolayer but on the cell number in relation to medium volume, and this dependence could be extrapolated to the origin. Addition of conditioned media from LPS-stimulated but not unstimulated cultures enhanced the ODC increase in sparsely plated cultures in response to a maximal concentration of LPS. The addition of polymyxin B, a reagent that blocks the effects of LPS, including the increase in ODC activity, did not totally inhibit the conditioned medium stimulation. This data indicates that two signals, LPS and a LPS-induced mediator, are involved in the induction of ODC activity in RAW264 cells.
...
PMID:Bacterial lipopolysaccharide induction of ornithine decarboxylase in the macrophage-like cell line RAW264: requirement of an inducible soluble factor. 257 74

Ornithine decarboxylase (ornithine carboxy lyase; EC 4.1.1.17) (ODC) from Tetrahymena thermophila was purified 6,300 fold employing fractionated ammonium sulfate precipitation, gel permeation chromatography on Sephadex G-150, ion exchange chromatography on DEAE-Sepharose CL-6B, and preparative isoelectric focussing. The product obtained in 24% yield was a preparation of the specific activity of 10,200 nmol CO2.h-1.mg-1. The purified enzyme was rather stable at 37 degrees C (14% loss of activity within 1 h). The molecular and catalytic properties of this enzyme were investigated. The isoelectric point was 5.7 and the molecular weight (MW) was estimated to be 68,000 under nondenaturing conditions. The pH optimum was between 6.0 and 7.0, the Km for the substrate L-ornithine was 0.11 mM, and the Km for the cofactor pyridoxal 5-phosphate was 0.12 microM; the product of ODC catalysis, putrescine, was a poor inhibitor with an estimated Ki of about 10 mM. The enzyme was inhibited competitively by D-ornithine with a Ki of 1.6 mM and by alpha-difluoromethylornithine with a Ki of 0.15 mM. The latter one, an enzyme activated irreversible inhibitor of mammalian ODC, inactivated the enzyme from T. thermophila at high concentrations with a half life time of 14 min. Other basic amino acids, e.g. L-lysine, L-arginine, and L-histidine, were neither substrates nor inhibitors of the enzyme, as were the diamines 1,3-diaminopropanol and cadaverine, the polyamines spermidine and spermine and the cosubstrate analogues pyridoxal and pyridoxamine-5-phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Properties of purified L-ornithine decarboxylase (EC 4.1.1.17) from Tetrahymena thermophila. 260 Aug 81

L-Arginine iminohydrolase (arginine deiminase, ADI) from Tetrahymena thermophila was purified approx. 75-fold by means of gel permeation chromatography. The Km of the purified enzyme for L-arginine was 412 +/- 25 microM and L-ornithine inhibited the reaction competitively with a Ki of 985 +/- 105 microM. D-Ornithine was a weak inhibitor with a Ki of greater than 10mM. The polyamines putrescine and spermidine inhibited ADI incompetitively with a Kii of 2.8mM for putrescine and 4.3mM for spermidine. Since the concentrations required for inhibition were within the range of the normal intracellular polyamine concentrations in Tetrahymena (maximally 14mM putrescine and 4mM spermidine), it is suggested that the polyamine effects on ADI are of regulatory nature. Thus, polyamine biosynthesis in Tetrahymena thermophila is regulated not only on the level of ornithine decarboxylase activity, but also on an earlier step, the supply of ODC with substrates.
...
PMID:Inhibition of L-arginine iminohydrolase (EC 3.5.3.6) from Tetrahymena thermophila by putrescine and spermidine: feedback control of polyamine biosynthesis. 261 Sep 30

1. Pretreatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] caused an increase in ornithine decarboxylase (EC 4.1.1.17) (ODC) activity in lipopolysaccharide (LPS)-stimulated human monocyte cell line, U937. 2. The increase in ODC activity was dose-dependent and preincubation-time dependent. 3. 26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D3 was ca 7 times more potent than 1,25-(OH)2D3 in increasing ODC activity. 4. Pretreatment with 1,25-(OH)2D3 also potentiated the activity of spermidine/spermine-N1-acetyltransferase in LPS-stimulated U937 cells. 5. Putrescine levels in cells pretreated with 1,25-(OH)2D3 increased ca 2-fold 4-8 hr after LPS addition. 6. However, pretreatment with 1,25-(OH)2D3 did not cause any increase in ODC mRNA level, suggesting that 1,25-(OH)2D3 may modulate polyamine metabolism at the posttranscriptional level rather than the transcriptional step.
...
PMID:Effect of 1 alpha,25-dihydroxyvitamin D3 on polyamine metabolism in human monocyte cell line-U937. 261 22

Barrett's esophagus is a condition in which the lower esophagus is lined with metaplastic columnar epithelium rather than normal stratified squamous epithelium. It is associated with an increased risk of cancer. Cancers developing in Barrett's epithelium are adenocarcinomas rather than the usual squamous cell esophageal cancers. Barrett's is somewhat unique among premalignant lesions, since it represents an entirely different epithelium from the normal and can therefore be histologically identified with certainty. The abnormal mucosa can be safely accessed repeatedly and its extent quantitated by endoscopy, thereby allowing serial follow-up studies and intervention trials. We are studying Barrett's esophagus as a model premalignant lesion for adenocarcinoma. Ornithine decarboxylase activity was increased in this lesion especially when dysplastic changes were present. Interestingly there was no relationship between polyamine levels and the increased ODC activity. Flow cytometric abnormalities have been demonstrated in Barrett's mucosa. Their significance remains to be determined. Epithelial cells from this lesion have been cultured and characterized. Clonal cytogenetic abnormalities were detected in some specimens. The cultured cells were used to test the effect of drugs on their growth. The ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, significantly inhibited growth even at low concentrations. A clinical intervention trial using 13-cis-retinoic acid has produced no change in the extent of the lesion in 11 evaluable patients. Nevertheless, the successful performance of this clinical study confirms that this lesion can be used for intervention trials aimed at reversing premalignant lesions.
...
PMID:Barrett's esophagus: a model premalignant lesion for adenocarcinoma. 261 47

Aging of IMR-90 human diploid fibroblasts in culture is accompanied by specific changes of polyamine metabolism including: (a) a fivefold decrease of serum-induced activity of ornithine decarboxylase (ODC1 EC 4.1.1.17); (b) a six to tenfold increase of polyamine catabolism; and (c) a reduction of putrescine uptake. These changes apparently led to a significant reduction of putrescine accumulation in senescent cells following serum stimulation. Since the induction of ODC is a mid-G1 event, the change of polyamine metabolism may be related to changes of expression of other cell-cycle-dependent genes during cellular aging. In addition to ODC gene, we have examined the expression of two early G1 genes, c-erbB and c-myc, and one late G1/S gene thymidine kinase, at mRNA levels, in both young and old IMR-90 cells. We have also compared the enzyme activities of two late G1/S genes, thymidine kinase and thymidylate synthetase, in young and old cells following serum stimulation. We did not observe significant changes of c-erbB, c-myc, and ODC mRNA levels during cellular senescence. However, we found that serum-induced mRNA level of thymidine kinase gene in old IMR-90 cells was significantly reduced compared to that in the young cells. Results also demonstrate that aging of IMR-90 cells was accompanied by significant decrease of both thymidine kinase and thymidylate synthetase activities. In view of the recognized importance of polyamines in growth regulation, it is possible that alteration of polyamine metabolism may contribute to the impairment of expression of some key G1/S genes and such impairment may contribute to the ultimate loss of dividing potential in senescent cells.
...
PMID:Polyamine metabolism and cell-cycle-dependent gene expression in IMR-90 human diploid fibroblasts during senescence in culture. 263 84

The polypeptide hormones governing the proliferation and differentiation of the mature immune system and hematopoiesis are collectively referred to as lymphokines. We have examined a number of biochemical and molecular events stimulated by several unique lymphokines which exhibit proliferative activity on lymphoid and myeloid cell lines. Interleukin-2 (IL-2) and several members of the colony-stimulating factors (IL-3, G-CSF, and GM-CSF) stimulate similar patterns of cellular phosphorylation including the prominent phosphorylation of a 68-kDa substrate present in numerous distinct lineage cell lines. The 68-kDa substrate is phosphorylated by protein kinase C on threonine residues and is primarily cytosolic. Another kinase system activated by either physiological ligand or synthetic diacylglycerol phosphorylated the 40S ribosomal protein in a dose-dependent manner. The increased phosphorylation of S6 protein was associated with enhanced chain elongation in vitro. The kinase responsible for the in situ phosphorylation, however, was not protein kinase-C (PK-C) but another physicochemically distinct Mg2+-dependent enzyme (termed S6 kinase). These studies suggested that, although PK-C was activated by diacylglycerol, another kinase, S6 kinase, was the effector enzyme involved in the phosphorylation of the 40S protein. IL-2 and all other CSFs tested stimulated the transcription of the nuclear protooncogenes c-fos, c-myc, and c-myb. In addition, ornithine decarboxylase mRNA accumulation was also stimulated. Phorbol esters also stimulated similar gene expression; however, cyclic AMP analog inhibited phorbol ester or ligand-induced c-myc expression and ODC mRNA accumulation. Cyclic AMP agonists are antiproliferative to all the growth factors tested. We have constructed complementary oligonucleotides, "antisense", against c-fos, c-myc, and other structural genes induced by the growth factors. Such antisense oligomers were capable of selectively deleting protein expression of the respective gene products and inhibited the biological action of the growth factors.
...
PMID:The molecular basis of immune cytokine action. 265 49

Sprague-Dawley rats (F-1) were fed a normal protein (19% casein, NP) or high protein (33% casein, HP) isoenergetic diet containing 15% corn oil prior to conception. Female pups (F-2) were also fed the maternal diet after weaning. At 7 wk of age, before saline or N-nitrosomethylurea (NMU) treatment, ornithine decarboxylase (ODC, EC 4.1.1.17) activity in mammary epithelium and liver tissue was significantly higher in the HP group than in the NP group. Eight weeks after saline treatment ODC activity in mammary tissue decreased in both groups, but remained significantly higher in the HP group. NMU treatment caused a sixfold increase in ODC activity in the mammary tissue in the HP group and a significantly lower response in the NP group. Liver ODC activity had a minimal response to NMU treatment. Changing from the HP to the NP diet 4 wk after NMU treatment reduced mammary ODC induction response but not tumor burden; changing from the NP diet to HP diet produced no change in ODC activity or tumor burden. Mammary tumor burden was positively related to dietary protein and mammary epithelium ODC activity prior to and following NMU treatment.
...
PMID:Dietary protein enhanced mammary ornithine decarboxylase activity and tumorigenesis in rats. 270 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---