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)

It has been suggested that the induction of ornithine decarboxylase (ODC) activity during pregnancy might contribute to the low ureagenic flux that enables the pregnant mother to spare nitrogen and support growth. Thus, we have studied the ODC activity, and urea and polyamine levels in livers of virgin and 21-day pregnant rats, either in a basal state or after the induction of ureagenesis by inducing diabetes in rats by streptozotocin injection. Diabetes led to a marked increase in circulating and liver urea levels in virgin rats. This response was significantly reduced in late-pregnant animals. Diabetes did not modify ODC activity in pregnant rats, which showed much lower activities than their virgin controls. Diabetes caused a depletion of the liver spermine content in pregnant rats. Spermidine levels were higher in both groups of pregnant animals than in their respective controls. Our results suggest first that the mechanisms contributing to spare nitrogen in the pregnant mother are likely to be present in diabetic pregnant animals and, second, that ODC does not mediate the metabolic adaptations leading to a low ureagenic flux and a higher nitrogen retention at the last stage of pregnancy.
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PMID:Ornithine decarboxylase activity and urea in liver of late-pregnant rats. Effect of streptozotocin-induced diabetes. 844 94

Polyamines have been proposed as specific mediators of estrogen action in breast cancer cells, but their exact role in this process is still controversial. As estrogens cooperatively interact with peptide growth factors in several hormonal responses, the involvement of polyamines in the synergistic effect of 17 beta-estradiol (E2) and insulin or insulin-like-growth factor I (IGF-I) on cell growth, polyamine pools, specific gene induction, and cell cycle progression was examined in estrogen-responsive MCF-7 and ZR-75-1 human breast cancer cells. Spermidine depletion induced by the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), resulted in complete cytostasis and loss of mitogenic response to either E2 or insulin (or IGF-I). In contrast, a steroidal antiestrogen blocked the mitogenic effect of E2, but only partly interfered with the synergistic stimulation of estrogen action by insulin. Whereas antiestrogen-resistant growth in insulin-treated cells was halted by DFMO, the antiestrogen did not further inhibit growth upon prior polyamine depletion. E2 and either IGF-I or insulin induced early increases in putrescine and spermidine, but not spermine, contents in both MCF-7 and ZR-75-1 cells. Moreover, spermidine depletion and decarboxylated S-adenosylmethionine accumulation induced by DFMO required prior mitogenic stimulation by E2 and/or IGF-I. The antiestrogen alone had only a limited effect on polyamine and nucleoside pools. DFMO did not interfere with the coordinate induction of the estrogen- and growth factor-inducible pS2 messenger ribonucleic acid by E2 and insulin even after a 5-day treatment with the drug. On the other hand, DFMO depressed the cycling fraction of E2/IGF-I-stimulated MCF-7 cell population far more dramatically than the antiestrogen and to less than that noted in mitogen-deprived cells. However, in ZR-75-1 cells, which have a much lower spermidine/spermine ratio than MCF-7 cells, specific inhibition of spermine synthase selectively antagonized the effect of E2 compared with that of insulin. These data indicate that spermidine has a permissive role for macromolecular synthesis and cell cycle traverse, but does not qualify as a limiting factor in estrogen receptor-mediated events per se in breast cancer cells. Moreover, polyamine depletion is an efficient complementary strategy to block the mitogenic action of peptide growth factors, which is only partly antagonized by antiestrogens.
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PMID:Permissive role of polyamines in the cooperative action of estrogens and insulin or insulin-like growth factor I on human breast cancer cell growth. 855 Jul 37

The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, two of the enzymes involved in the synthesis of the polyamines, were found to be high in follicle-rich homogenates of sheep skin, and to be responsive to the nutrition of the animal. Systemic provision of the inhibitor of ornithine decarboxylase, alpha difluoromethylornithine, markedly altered the length, diameter, and composition of the fiber, the last being accompanied by an increase in the proportion of the fiber occupied by paracortical cells and an increase in the level of mRNA encoding a cysteine-rich family of keratin proteins. The growth of wool follicles cultured in media containing alpha-difluoromethylornithine was not inhibited, even at high concentrations. In contrast, low concentrations of methylglyoxal (bis)guanylhydrazone, the inhibitor of S-adenosylmethionine decarboxylase, completely inhibited fiber growth in culture follicles. Addition of spermidine to the media overcame this inhibition but spermine had no effect. Further evidence that spermine is not required for normal follicle function was provided by incubating follicles with the specific inhibitor of spermine synthase, n-butyl-1,3-diaminopropane. This inhibitor, even at high concentrations, had no effect on fiber growth in vitro. Spermidine partially overcame the growth depression that occurred in follicles cultured in methionine-deficient media, suggesting that part of the requirement for methionine is for spermidine synthesis in the follicle. These investigations provide strong evidence that the polyamines in general , and spermidine in particular, play a major role in hair growth.
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PMID:Inhibition of polyamine synthesis alters hair follicle function and fiber composition. 860 24

Activation of ornithine decarboxylase (ODC), the initial enzyme in polyamine synthesis, and accumulation of putrescine are thought to mediate pathological processes in the ischemic and traumatized brain. Past studies have separately investigated either ODC or polyamines after head injury. The purpose of the present study was to quantify both ODC activity and polyamines in the rat parietal cortex before and after controlled cortical impact injury. Adult, male rats underwent a right craniectomy and were subjected to a 5 m/sec, 2-mm deformation impact injury. Rats were sacrificed 1, 4, 8, and 24 h postimpact and tissues from the injured (right) and contralateral (left) hemisphere were analyzed for ODC and polyamines. ODC activity was determined by measuring the decarboxylation of [14C]ornithine to putrescine. Putrescine, spermidine, and spermine were determined by high performance liquid chromatography. Cortical impact induced a 10- to 20-fold increase in ODC activity and a 4- to 5-fold increase in putrescine in the ipsilateral cortex. Spermidine and spermine did not significantly increase in the ipsilateral (right) cortex compared to controls (right cortex). In contrast, there was a slight increase in spermidine content in the contralateral (left) cortex after injury. The delayed increase in ODC activity and accumulation of putrescine may mediate pathophysiological changes observed after head injury.
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PMID:Activation of ornithine decarboxylase and accumulation of putrescine after traumatic brain injury. 891 65

Intragastric administration of 3.4 M NaCl damages the gastric mucosa and increases the activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis. Polyamines are essential for the repair of gastric erosions. Little is known about the restitution of damaged mucosa except that cell migration is essential. Actin is the principal cytoskeletal protein and is essential for migration. This investigation determines the relationship between polyamines, actin, and gastric healing. Rats were fasted for 22 h and given 1.0 ml of 3.4 M NaCl intragastrically and killed 1, 2, 4, 8, and 10 h later. The mucosa was assayed for ODC activity and stained for G- and F-actin. F-actin was concentrated below the damaged mucosa at 1.5, 2, and 4 h. There was no increase in F-actin distribution at any time point, when NaCl-treated animals were given alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC. In addition, DFMO significantly prevented the healing of the mucosal lesions. Spermidine treatment after DFMO + NaCl significantly prevented the effects of DFMO. Cytochalasin D, a potent actin-disrupting drug, significantly delayed normal gastric mucosal healing. The endogenous polyamines increased significantly in NaCl animals. Data indicate that increases in polyamine synthesis after damage influence the distribution of F-actin in vivo, which may play a part in the healing of mucosal erosions.
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PMID:Relationship between polyamines, actin distribution, and gastric healing in rats. 894 5

The induction of antizyme by spermidine and the resulting enhancement of ornithine decarboxylase (ODC) degradation have been well studied; however, little is known about the mechanism whereby elevated spermidine levels decrease synthesis of the polyamine biosynthetic enzyme. To evaluate the relative contribution of inhibited synthesis, as distinct from enhanced degradation of ODC, spermidine levels were manipulated in a variant cell line that overproduces a stable form of ODC. Spermidine did not selectively inhibit ODC synthesis in these variant cells, supporting the concept that spermidine diminishes ODC synthesis in normal cells owing to enhanced degradation of the protein in the presence of elevated antizyme levels. This model was further investigated in vitro by use of rabbit reticulocyte lysate, which catalyses simultaneous ODC mRNA translation and antizyme-stimulated degradation of ODC protein. Antizyme strongly repressed the incorporation of labelled amino acids into normal rat ODC. Unexpectedly it also diminished the apparent translation of ODC mRNA species coding for enzyme forms that are not destabilized by the post-translational addition of antizyme. The effect of antizyme on ODC translation was not observed in wheatgerm extract, in which there is no antizyme-induced degradation. Further, deletion of a short segment of antizyme necessary for the destabilization of ODC (amino acid residues 113-118) resulted in a form that bound ODC but did not diminish its apparent translation. These results suggest that the co-translational addition of antizyme to ODC results in a complex that is different from, and innately less stable than, that formed when antizyme is added post-translationally.
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PMID:Feedback repression of ornithine decarboxylase synthesis mediated by antizyme. 900 59

The following observations are conjointly indicative of the presence of distinct energy-dependent, saturable and multiple polyamine transport systems in Leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. Spermidine was influxed with as much as seven times higher rate than putrescine, while both spermidine and putrescine transporters exhibited equally high affinity for the respective polyamine. N-Ethylmaleimide arrested the complete functionality of both the transporters which could be restored by reduced glutathione. Putrescine transporter did not recognize spermine but spermidine was recognized to some extent, while spermidine transporter significantly recognized spermine but putrescine was absolutely spared. A few aromatic diamines viz., diaminobiphenyl and the analogs as well as aliphatic diamines viz., cadaverine and agmatine were selectively recognized by the putrescine transporter only. L. donovani promastigotes grown in presence of alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, registered marked upregulation of putrescine transport while spermidine transport was only marginally induced. PA transport systems provide the alternative pool of polyamines in L. donovani promastigotes in the absence of an adequate intracellular PA repertoire.
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PMID:Polyamine transport systems of Leishmania donovani promastigotes. 915 Apr 19

The pathophysiological impact of infections with chloroquine-susceptible (CQS) and chloroquine-resistant (CQR) strains of Plasmodium berghei in Mastomys natalensis was studied with respect to changes in polyamine profiles in various tissues. Both CQS and CQR infections produced similar changes in polyamine profiles of various tissues. Maximum increase was recorded in spleen followed by liver and lungs. Renal, cardiac and cerebral tissues did not register significant changes. An increase in spermidine level was more prominent as compared to putrescine and spermine, leading to an overall increase in spermidine/spermine ratio. This ratio is an important index of cellular proliferation. Liver did not show considerable change in the activities of ornithine decarboxylase and S-adenosyl methionine decarboxylase, the regulatory enzymes of the polyamine biosynthetic pathway. Spleen however, registered marked induction of both the enzymes which was more prominent in the CQS infection than CQR. Normal erythrocytes contained traces of polyamine while the erythrocytes loaded with P. berghei parasites exhibited appreciably higher polyamine levels. Spermidine was detected in about five-fold higher concentrations than putrescine and spermine which were detected in equimolar levels. Again, CQS as well as CQR P. berghei, exhibited qualitatively and quantitatively similar polyamine profiles thus ruling out a role of polyamines in CQ-resistance in malaria.
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PMID:Polyamine metabolism in various tissues during pathogenesis of chloroquine-susceptible and resistant malaria. 941 68

Spermidine/spermine N1-acetyltransferase (SSAT), rate-limiting enzyme of polyamine interconversion, has been demonstrated to play an important role in malignant transformation of cells. We examined the involvement of altered polyamine metabolism in the colonic carcinogenesis, using 1,2-dimethylhydrazine (DMH)-induced rat colon tumor model. Following findings were obtained: i) Ornithine decarboxylase demonstrated high activity from the early phase in colon mucosa, and increased significantly in tumors. ii) Spermidine and spermine levels gradually elevated in DMH-treated mucosa, while putrescine increased significantly in tumor tissues. iii) SSAT activity increased gradually in DMH-treated colon mucosa, which preceded elevation of tissue putrescine level, and coincided with tumor development. In conclusion, elevation of putrescine level and induction of SSAT activity are suggested to have a close association in colonic carcinogenesis.
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PMID:Elevation in putrescine level and spermidine/spermine N1-acetyltransferase activity coincide with tumor development in 1, 2-dimethylhydrazine-induced rat colon. 945 6

Polyamines serve as natural substrates for the transglutaminase that catalyzes covalent cross-linking of proteins and is involved in cellular adhesion and proliferation. This study tests the hypothesis that intracellular polyamines play a role in the regulation of transglutaminase expression in rat small intestinal crypt cells (IEC-6 cell line) and human colon carcinoma cells (Caco-2 cell line). Treatment with alpha-difluoromethylornithine (DFMO; a specific inhibitor of polyamine synthesis) significantly depleted the cellular polyamines putrescine, spermidine, and spermine in both cell lines. In IEC-6 cells, polyamine depletion was associated with a decrease in the levels of transglutaminase mRNA. In Caco-2 cells, however, polyamine depletion significantly increased the levels of transglutaminase mRNA and enzyme activity. In both cell lines, ornithine decarboxylase mRNA levels increased and protooncogene c-myc mRNA decreased in the presence of DFMO. Addition of polyamines to cells treated with DFMO reversed the effect of DFMO on the levels of mRNA for these genes in both lines. There was no significant change in the stability of transglutaminase mRNA between control and DFMO-treated IEC-6 cells. In contrast, the half-life of mRNA for transglutaminase in Caco-2 cells was dramatically increased after polyamine depletion. Spermidine, when given together with DFMO, completely prevented increased half-life of transglutaminase mRNA in Caco-2 cells. These results indicate that 1) expression of transglutaminase requires polyamines in IEC-6 cells but is inhibited by these agents in Caco-2 cells, 2) polyamines modulate transglutaminase expression at the level of mRNA through different pathways in these two cell lines, and 3) posttranscriptional regulation plays a major role in the induction of transglutaminase mRNA in polyamine-deficient Caco-2 cells.
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PMID:Differences in transglutaminase mRNA after polyamine depletion in two cell lines. 948 43


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