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)

Previous studies in our laboratory demonstrated the alteration in the physical state of synaptosomal membrane lipids and proteins in ischemia/reperfusion injury using selective spin labels and electron paramagnetic resonance spectroscopy [Hall et al. (1995) Neuroscience 61, 84-89]. Since many investigations have provided evidence for free radical generation during ischemia/reperfusion injury, we investigated whether a free radical scavenger would prevent the membrane damage, in gerbils. Further, experiments to determine if a secondary effect of polyamine generation at 14 h reperfusion could be blocked by this free radical scavenger or by an inhibitor of ornithine decarboxylase were also carried out. The alterations in synaptosomal membrane integrity observed during ischemia/reperfusion injury were selectively neutralized by treatment with the free radical spin trap N-tert-butyl-alpha-phenylnitrone or an inhibitor of ornithine decarboxylase, difluoromethylornithine. Administration of N-tert-butyl-alpha-phenylnitrone prior to ischemia totally abrogated both lipid and protein alterations observed at 1 and 14 h reperfusion. Pretreatment with difluoromethylornithine neutralized only the 14 h change in lipid label motion. Treatment with N-tert-butyl-alpha-phenylnitrone at 6 h post ischemia showed only a slight attenuation of the 14 h lipid effect and no change in the protein effect. Difluoromethylornithine treatment at 6 h post ischemia negated the 14 h ischemia/reperfusion injury-induced lipid effect and had no effect on the protein change. These data support previous suggestions that free radicals and polyamines play a critical role in neuronal damage and cell loss following ischemia/reperfusion injury and that the polyamine effect is dependent upon free radical generation during ischemia/reperfusion injury.
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PMID:Prevention of ischemia/reperfusion-induced alterations in synaptosomal membrane-associated proteins and lipids by N-tert-butyl-alpha-phenylnitrone and difluoromethylornithine. 855 52

The expression of the immediate early genes (IEG)s c-fos, c-jun and zif/268, and the genes coding for ornithine decarboxylase (ODC) and its regulatory protein antizyme (AZ), was studied in rat small intestine following transient ischemia. The ischemic stimulus for 10 min alone did not alter the expression of these genes. A rapid and transitory induction of all IEG mRNAs occurred in a coordinated manner peaking at 30 min following recirculation and returned to basal levels 3 hr after recirculation. Protein products of the IEGs accumulated in the smooth muscle layer of the intestine by 2-3 hr after recirculation. Expression of both ODC and AZ mRNAs initially decreased to 70% of control levels 1 hr after recirculation but markedly increased at 2 to 4 hr after recirculation. The functional significance of these changes in gene expression in relation to tissue integrity and function after the ischaemia/reperfusion is discussed.
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PMID:Induction of immediate-early, ornithine decarboxylase and antizyme gene expression in the rat small intestine after transient ischaemia. 864 18

Cigarette smoking during pregnancy exposes the fetus to both nicotine and hypoxia/ischemia; postnatal exposure to second-hand smoke also involves substances that cause hypoxia (CO, HCN). Although developing cardiac cells are more resistant to hypoxia-induced damage than are mature cells, we examined whether nicotine affects this resistance, either when exposure is concurrent with hypoxia, or when animals are exposed to nicotine prenatally and receive subsequent hypoxic exposure. One, 8-, or 15-day-old rats exposed to 7% O2 for 2 hr all showed inhibition of cardiac DNA synthesis. By contrast, administration of nicotine at either low (0.3 mg/kg) or high (3 mg/kg) doses failed to alter DNA synthesis. To examine effects on cells that were not undergoing mitosis, we examined ornithine decarboxylase (ODC), an enzymatic marker for cell damage. One day old rats showed inhibition of ODC by hypoxia, a response that represents preservation of cell integrity; by 8 days of age, ODC was increased by hypoxia, evidence of cell damage. The high dose of nicotine evoked an increase in ODC at all ages and the low dose exacerbated the effects of hypoxia at 8 days of age. Prenatal nicotine exposure caused a transient inhibition of cardiac DNA synthesis but did not produce evidence of cell damage (ODC, protein synthesis markers) by itself, nor did it alter the effect of a subsequent postnatal exposure to hypoxia. These results suggest that cardiac cell damage could emerge as a consequence of concurrent, repeated exposures to nicotine and hypoxia. Such effects could contribute to the elevated incidence of perinatal morbidity/mortality and Sudden Infant Death Syndrome associated with smoking.
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PMID:Does concurrent or prior nicotine exposure interact with neonatal hypoxia to produce cardiac cell damage? 883 53

Agmatine, product of arginine decarboxylation, is known to occur mainly in bacteria and plants where it serves as a precursor for the synthesis of polyamines. Recently however, agmatine and arginine decarboxylation were detected in mammalian brain. Here we examined changes in rodent brain arginine decarboxylation during cerebellum development and after global forebrain ischemia and compared them to changes in ornithine decarboxylase, the enzyme catalyzing the first limiting step in polyamine synthesis. The findings suggest that (1) arginine decarboxylation is transiently increased during development and after ischemia in parallel to ornithine decarboxylase activity. (2) Arginine decarboxylation reaction is catalyzed by ornithine decarboxylase. (3) Decarboxylation of both ornithine and arginine becomes more pronounced in membrane fractions, rather than in the cytosol, during brain maturation. (4) During development, ornithine decarboxylase activity is reduced in the cytosol, but increased in the membrane fractions.
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PMID:Arginine and ornithine decarboxylation in rodent brain: coincidental changes during development and after ischemia. 889 85

Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.
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PMID:Polyamines induce blood-brain barrier disruption and edema formation in the rat. 898 32

Transient global cerebral ischemia has been shown to induce marked changes in the polyamine pathway with a significant increase in putrescine, the product of the ornithine decarboxylase reaction. This study examined the relationship between tissue and extracellular polyamines and regional cerebral blood flow and brain edema. Six hours of focal ischemia in cats (n = 10) was produced by permanent middle cerebral artery occlusion. Extracellular polyamines were measured in extracellular fluid obtained by microdialysis. Regional cerebral blood flow using laser Doppler flowmetry and specific gravity, an indicator of brain edema, were measured in contralateral (non-ischemic), penumbra and densely ischemic brain regions. A significant increase in the tissue putrescine level was found in the penumbra but there was no difference in the putrescine levels between contralateral and densely ischemic regions. There was no significant change in the spermidine and spermine levels in the three regions. Extracellular levels of putrescine and spermidine were found to be significantly lower than the tissue levels and no change in polyamines was observed in any region. Significant edema formation was observed in densely ischemic and penumbra regions. This is the first demonstration that tissue putrescine is increased in the penumbra region, an area of incomplete ischemia that is developing brain edema.
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PMID:Regional brain polyamine levels in permanent focal cerebral ischemia. 910 40

S-Adenosyl-L-methionine decarboxylase (SAMdc) and L-ornithine decarboxylase (ODC) are major enzymes regulating polyamine synthesis. Following ischemia, putrescine content increases as a result of posttraumatic activation of ODC and inhibition of SAMdc. These alterations are thought to mediate edema and cell death. The purpose of this study was to quantify SAMdc activity and edema in the brain following controlled cortical impact injury. Anesthetized adult male rats underwent a right parietal craniectomy and were subjected to cortical impact injury. Tissues were obtained from three bilateral regions: parietal cortex, motor area (CPm); parietal cortex, somatosensory area (CPs); and the pyriform cortex (CPF). SAMdc activity was determined in the postmitochondrial fraction from homogenates of fresh, unfrozen tissues by measuring the decarboxylation of S-adenosyl-L-[carboxyl-14C]methionine. Basal SAMdc activity was determined in unoperated rats, and regional differences were noted: Activity was lower in the CPF than in the CPm and CPs. SAMdc activity decreased to the greatest extent in the ipsilateral CPm (impact site) from 1 to 72 h following traumatic brain injury. Significant edema was found in the ipsilateral CPm 1, 8, 16, 24, and 48 h after injury. Decreased SAMdc activity impairs the conversion of putrescine to polyamines and may contribute to delayed pathological changes in the brain after traumatic injury.
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PMID:S-adenosylmethionine decarboxylase activity is decreased in the rat cortex after traumatic brain injury. 920 18

A total of 175 rats were divided into: (1) a sham operation group, in which the liver was slightly mobilized after laparotomy; (2) a control group in which 68% of the liver was resected without the blockade of blood flow; (3) an ischemia + hepatectomy group, in which the vessels entering the right and caudate lobes were clamped for 30 min, and the nonischemic lobes were resected; (4) a DFMO + ischemia + hepatectomy group, in which the same procedure as for the ischemia + hepatectomy group was performed, but the animals received alpha-difluoromethylornithine (DFMO); (5) a DFMO + Put + ischemia + hepatectomy group, in which the animals underwent the same procedure, but were given putrescine (Put) in addition to DFMO. There were 6 to 7 rats in each of the five groups. The putrescine level and ornithine decarboxylase (ODC) activity were significantly higher in the ischemia + hepatectomy group than in the control group, but were markedly decreased in the DFMO + ischemia + hepatectomy group. However, the lipid peroxide level was significantly higher in the DFMO + ischemia + hepatectomy group than in the ischemia + hepatectomy group. The incorporation of [3H]thymidine in the DFMO + ischemia + hepatectomy group was significantly lower than that in the control group. The increase in the lipid peroxide level and the decrease in [3H]thymidine found in the DFMO + ischemia + hepatectomy group tended to be reversed by the administration of putrescine. These results suggest that putrescine suppressed the production of lipid peroxides and promoted DNA synthesis in regenerating the liver after ischemia-reperfusion injury.
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PMID:The role of polyamines in liver regeneration after hepatectomy with ischemic injury. 930 6

Apoptosis after ischemia-reperfusion (I/R) was characterized in rat small intestine. Under halothane anesthesia, the superior mesenteric artery in the rat was occluded for 15 or 60 min, followed by reperfusion. Ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after I/R. Some rats were pretreated with alpha-difluoromethylornithine (DFMO) to examine the relationship between intestinal apoptosis and ornithine decarboxylase (ODC) activity. The percentage of fragmented DNA significantly increased just after ischemia and peaked at 1 h after reperfusion in the jejunum and ileum. These increases were significantly higher in the 60-min ischemia group compared with the 15-min ischemia group. This increase decreased 6 h after reperfusion. The results were corroborated by histological evaluations of the intestine under the same conditions. DFMO completely abolished elevation of ODC activity 6 h after reperfusion but did not change the percentage of fragmented DNA. Apoptosis in rat small intestine was induced by ischemia of the gut, and this process was exacerbated by reperfusion. The changes in apoptosis were independent of ODC activity.
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PMID:Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa. 948 79

Ornithine decarboxylase (ODC) is considered the rate-limiting enzyme in polyamine biosynthesis. An increase in putrescine (a natural polyamine) synthesis after central nervous system (CNS) injury appears to be involved in blood-brain barrier dysfunction, development of vasogenic edema and neuronal death. An improved method is described to determine the ODC activity as well as polyamine levels from the same brain tissue. The polyamine results showed no significant differences from data obtained with the conventional assay. The advantages of this method are to: (1) minimize the number of animals needed for the study, and (2) eliminate any internal inconsistencies resulting from use of two independent groups of animals for ODC and polyamine measurements. Using this method, ODC activities and polyamine levels were measured in cortices and hippocampi from global transient ischemia of gerbils and traumatic brain injury (TBI) of rats.
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PMID:Simultaneous assay of ornithine decarboxylase and polyamines after central nervous system injury in gerbil and rat. 985 4


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