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)

Polyamine (tissue) concentrations have been studied in hippocampus and temporal neocortex from patients with temporal lobe epilepsy. Depth electrode recordings demonstrated hippocampal origin of the seizures, the temporal neocortex being involved during the discharge propagation. Neuropathological examination of excised tissues showed glial proliferation or glioma in Ammon's horn (CA), whereas the temporal neocortex did not exhibit any histological abnormality. Polyamine (putrescine or PUT, spermidine or SPD, spermine or SPM) concentrations were determined on surgical samples from the hippocampus and various areas of temporal neocortex. Human post-mortem tissue from temporal lobe regions was used for controls. In post-mortem controls and temporal neocortex specimens from epileptic patients, polyamine levels were similar (in nmol/g wet weight: PUT = 40-100; SPD = 200-350; SPM = 100-200). In CA, polyamine levels exhibited striking changes: SPD content was significantly increased (350-700 nmol/g) while SPM was lowered (50-100). PUT was only increased in CA invaded by the tumoral process (100-180). Accordingly, a very high SPD/SPM molar ratio in the abnormal CA region was observed, indicating an acceleration of polyamine neosynthesis which is usually related to ornithine decarboxylase induction. Metabolic changes in polyamines appear to be selective of human epileptic hippocampus. A relationship between glial proliferation (gliosis or neoplasia), epileptic firing and polyamines is discussed.
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PMID:Polyamine metabolism in epileptic cortex. 139 40

Ornithine decarboxylase (ODC), which initiates the biosynthesis of the polyamines putrescine, spermidine, and spermine, is encoded by the spe-1 gene of the fungus Neurospora crassa. This gene and its cDNA have been cloned and sequenced. The gene has a single 70-nucleotide intron in the coding sequence. The cDNA, comprising the entire coding region, recognizes a single 2.4-kb mRNA in Northern (RNA) blots. The mRNA transcript, defined by S1 mapping, has an extremely long, 535-base leader without strong secondary-structure features or an upstream reading frame. The translational start of the protein is ambiguous: a Met-Val-Met sequence precedes the Pro known to be the N terminus of the ODC polypeptide. The polypeptide encoded by the N. crassa spe-1 gene (484 amino acids) has 46% amino acid identity with that of Saccharomyces cerevisiae (466 amino acids) and 42% with that of mouse (461 amino acids). Alignment of the longer N. crassa sequence with S. cerevisiae and mouse sequences creates gaps in different sites in the S. cerevisiae and mouse sequences, suggesting that N. crassa ODC is closer to an ancestral form of the enzyme than that of either yeast or mouse ODC. N. crassa ODC, which turns over rapidly in vivo in the presence of polyamines, has two PEST sequences, found in most ODCs and other proteins with rapid turnover. In striking contrast to other eucaryotic organisms, the variation in the rate of ODC synthesis in response to polyamines in N. crassa is largely correlated with proportional changes in the abundance of ODC mRNA. Spermidine is the main effector of repression, while putrescine has a weaker effect. However, putrescine accumulation appears to increase the amount of active ODC that is made from a given amount of ODC mRNA, possibly by improving its translatability. Conversely, prolonged starvation for both putrescine and spermidine leads to the differentially impaired translation of ODC mRNA.
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PMID:Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA. 153 Aug 78

The purpose of this study was to examine whether luminal polyamines administered exogenously accelerate the repair of stress-induced intestinal mucosal damage in rats. Rats were fasted for 22 hours, placed in restraint cages, and immersed in water to the xiphoid process for 6 hours. Animals were killed either immediately after the period of stress or at 4, 12, and 24 hours thereafter. Duodenal mucosa was examined histologically, and ornithine decarboxylase activity and polyamine levels were measured. Repair of duodenal mucosa after stress was extensively delayed by administering 500 mg/kg DL-alpha-difluoromethylornithine (DFMO) IP. DFMO also inhibited ornithine decarboxylase activity and prevented increases in duodenal mucosal polyamine content. Intragastric administration of the polyamines, putrescine, spermidine, and spermine (100 mg/kg), immediately after stress significantly prevented the decreased rate of repair caused by DFMO. Spermidine or spermine accelerated healing better than putrescine in the DFMO-treated rats. Spermine also significantly increased the normal rate of repair of stress-induced damage. The delayed recovery of mucosal DNA, RNA, and protein content following stress in the DFMO-treated rats was prevented by exogenous polyamines. The reduced levels of duodenal mucosal spermidine and spermine in stressed rats treated with DFMO returned toward control levels after administration of exogenous spermidine. These results indicate that (a) luminal polyamines effectively substitute for endogenously synthesized polyamines in the repair process of the duodenal mucosa, (b) luminal polyamines can increase the normal healing rate and, (c) polyamines accelerate healing by increasing both an early phase and a later phase dependent on cell renewal.
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PMID:Luminal polyamines substitute for tissue polyamines in duodenal mucosal repair after stress in rats. 155 19

The intrastriatal injection of N-methyl-D-aspartate (NMDA) (250 nmol) produced a delayed and marked increase in striatal ornithine decarboxylase (ODC) activity and putrescine levels which peaked 6-15 h following the injection of NMDA. Striatal ODC activity subsequently returned to normal values while putrescine levels remained significantly elevated for up to 4 days following the lesion. NMDA produced an early and progressive decline in striatal spermine and spermidine levels, preceding the increase in ODC activity, with a maximum effect 2 h following injection. Spermidine levels returned to normal 6 h post-NMDA infusion, and subsequently increased to above normal levels 36 h and 4 days after the infusion of NMDA. This late increase in striatal spermidine levels paralleled an increase in the binding of the glial cell/macrophage marker [3H]PK 11195. Spermine levels tended to return to normal values 6 h after the injection of NMDA but may be further depressed at later intervals (15 h to 4 days). The intrastriatal injection of saline also resulted in a delayed increase in striatal ODC activity and putrescine levels, but these changes were minor compared to those produced by NMDA. Intrastriatal saline injection provoked no consistent change in striatal spermine or spermidine levels. The changes in polyamine metabolism produced by the intrastriatal injection of kainic acid (4 nmol) were only analysed at 6 and 15 h following injection but were qualitatively similar to those produced by NMDA although perhaps following a slightly more delayed time-course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of N-methyl-D-aspartate and kainate lesions of the rat striatum on striatal ornithine decarboxylase activity and polyamine levels. 165 82

The purpose of this study was to examine whether luminal polyamines can substitute for tissue polyamines in the healing process of gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately or at 4, 12, or 24 h after the period of stress. Stress significantly increased ornithine decarboxylase (ODC) activity and tissue polyamine content. Mucosal polyamine levels peaked 4 h after stress and remained significantly elevated for 12 h. The healing process, which was significant by 12 h, was inhibited by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC. DFMO totally prevented the marked increases in ODC and polyamine levels that usually followed stress. Oral administration of polyamines, putrescine, cadaverine, spermidine, or spermine, immediately after stress increased the normal rate of healing and prevented the inhibition of repair caused by DFMO. Spermidine or spermine accelerated healing better than putrescine or cadaverine. The delayed recovery of mucosal DNA, RNA, and protein content after stress in the DFMO-treated rats was also significantly prevented by exogenous polyamines. The reduced amounts of gastric mucosal spermidine and spermine in rats treated with DFMO returned toward control levels after administration of exogenous spermidine (100 mg/kg). These results show that 1) increased levels of polyamines provided by ODC are absolutely required for normal healing of gastric mucosal stress ulcers, 2) the polyamines are active from the luminal side, and 3) polyamines accelerate healing at least partly through a mechanism involving cell renewal.
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PMID:Luminal polyamines stimulate repair of gastric mucosal stress ulcers. 169 28

DL-alpha-Difluoromethylornithine (DFMO) is a specific inhibitor of the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC). DFMO (1 mM) added to C57BL/6 anti-DBA/2 murine mixed lymphocyte cultures (MLC) inhibited cytolytic T lymphocyte (CTL) activity on days 3 and 5 by 88% and 96%. Putrescine (PUT; 1 mM) and spermidine (SPD; 0.01 mM) reversed DFMO inhibition, indicating that DFMO inhibition was caused by ODC antagonism. T helper (Th) cell and accessory cell functions were not affected since DFMO did not inhibit MLC proliferation or lymphokine production. Furthermore, exogenous IL-1, IL-2, IL-4, interferon-gamma, or a rat Con A supernatant failed to abrogate DFMO inhibition. Inhibition was reversible within 48 h of removing cells from DFMO; moreover, subsequent development of DFMO-blocked CTL did not require CD4+ cells. Clonal expansion of CTL treated with 1 mM DFMO for three days in MLC, determined by subsequent analysis in limiting dilution microcultures, was only approx. 1 cell division less than control. These results indicate DFMO inhibition is exerted directly on the CTL, and that the process of differentiation was more affected by a reduction in polyamine biosynthesis than proliferation. This may be a useful model to the study stages and events of CTL development, and the roles played by polyamines in supporting these processes.
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PMID:Difluoromethylornithine (DFMO) arrests murine CTL development in the late, pre-effector stage. 183 10

Previous studies have shown that melanoma is very sensitive to inhibitors of polyamine biosynthesis. In this work, we have studied changes in polyamine concentrations and the activities of two key enzymes of their biosynthetic pathway at different stages of growth of Harding-Passey melanoma transplanted to mice. We found that the peak activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase corresponded with maximal rate of tumour growth, but showed no clear correlation with polyamine content of the tumour. The ratio of spermidine to spermine was extremely low, decreasing from 0.80 to 0.46 through the different stages of growth. The half-lives of ornithine decarboxylase and S-adenosylmethionine decarboxylase were 15 and 30 min, respectively. The half-life of melanomal S-adenosylmethionine decarboxylase increased to 110 min in difluoromethylornithine-treated animals. The activities of both decarboxylases were markedly decreased by administration of exogenous polyamines, ornithine decarboxylase being more sensitive than S-adenosylmethionine decarboxylase. Spermidine and spermine were more effective than putrescine or diaminopropane. The results indicate that the melanoma ornithine and S-adenosylmethionine decarboxylases behave in the same way as the enzymes from non-neoplastic tissues.
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PMID:Polyamine metabolism in Harding-Passey murine melanoma. 184 14

Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline-treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure.
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PMID:The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats. 191 71

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 effect of brief periods of experience in an enriched environment (7 hours per day for 3 days), and of inhibition of polyamine synthesis was studied in four brain regions: occipital cortex, remaining cortex, subcortex and cerebellum plus medulla. Polyamine synthesis was inhibited by alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. DFMO caused a 30-50% decrease in putrescine content in all brain areas, irrespective of the environmental treatment. Spermidine was decreased by the inhibitor in subcortex and in cerebellum plus medulla, while spermine was increased in remaining cortex. The regional differences in inhibitor effect suggest that the regulation of polyamine metabolism varies among the four brain areas. Experience increased the weight and spermidine content of remaining cortex and decreased putrescine content of occipital cortex. Noncortical areas were not affected. The effects of experience on polyamine levels were somewhat increased by DFMO. Therefore, experience did not have a generalized effect on polyamine levels; rather, each polyamine responded in a specific manner. In addition, polyamine levels were affected only in those brain areas which are known from previous studies to respond to environmental stimulation with weight increase. These facts suggest that polyamines might have a role in the regulation of experience-induced plasticity.
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PMID:Experience affects cortical but not subcortical polyamines. 210 54


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