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)

To assess whether ornithine decarboxylase (ODC) is involved in mucosal repair after ischemia-reperfusion (I/R), two approaches were used: 1) measurement of mucosal ODC activity at different intervals after I/R, and 2) inhibition of ODC activity with alpha-difluoromethylornithine (DFMO, an irreversible inhibitor). In the first series of experiments, rats were allowed to recover after superior mesenteric arterial occlusion (10 min) before harvesting the intestinal mucosa for measurement of ODC activity. ODC activity increased markedly 6 h after I/R, and greater than 72 h were required for enzyme activity to return to normal. DFMO treatment completely abolished the I/R-induced increase in ODC activity. In another series of experiments, rats with an intestinal lymph fistula were infused intraduodenally at 3 ml/h with vehicle or 2% DFMO in vehicle immediately after I/R. Lipid absorption was measured at 24 and 48 h after I/R. In the DFMO group, lymph radioactive lipid output at 24 h after I/R was significantly lower compared with time-matched sham-operated controls. Lymph lipid output in rats receiving the vehicle was restored to a normal level at 48 h after I/R. However, this restoration of normal lymphatic lipid transport at 48 h I/R was not observed in the DFMO group. These observations indicate that ODC activity plays an important role in the repair process that results in complete restoration of mucosal function 2 days after I/R.
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PMID:Ornithine decarboxylase is involved in repair of small intestine after ischemia-reperfusion in rats. 188 98

Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene.
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PMID:Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. 193 91

We have examined the effects of systemic kainic acid (KA) administration (9 mg/kg, i.p.) on rat behavior, brain damage, and polyamine levels and the action of the specific ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) on these effects. KA elicited convulsant activity in 63% of the animals. In the acute convulsant phase (1-3 h after KA), a rapid decline (-39% at 3 h) of spermidine content in frontal cortex was found. After the acute convulsant phase, levels of hippocampal spermidine and spermine were reduced (-70 and -66%, respectively, at 8 h). A dramatic increase of putrescine content (68.1, 1,382, and 336% at 8 h, 24 h, and 9 days, respectively, after KA) was found, associated with histological signs of cortical brain damage (ischemia and necrosis). There was a close relationship between the concentration of putrescine and signs of delayed toxicity (body weight losses) 24 h and 9 days after KA. DFMO partially antagonized the convulsant activity and reduced the increased putrescine levels to approximately 50% of values in KA-treated animals at 24 h but did not change the pattern of histological damage. The role of polyamines in the early and late phases of KA-induced neurotoxicity is discussed.
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PMID:Changes in polyamine levels in rat brain after systemic kainic acid administration: relationship to convulsant activity and brain damage. 205 Nov 59

Steady-state levels of messenger RNA (mRNA) for different members of the heat-shock protein 70 gene family were studied in rat livers reperfused after non-necrogenic ischemia. The expression of constitutive hsc 73 gene decreases during ischemia, returns to normal upon reperfusion, and increases 4 hr after restoration of blood flow. Reperfusion induces the expression of another hsp 70 gene family member (the so-called inducible hsp 70 gene), which remains at high levels for at least 7 hr. The induction of hsp 70 family genes is preceded by activation of the cellular oncogene c-fos, the most prompt change in gene expression detected in reperfused liver. Run-on experiments demonstrate that the increased expression of these genes is largely dependent on activation of transcription. Changes in the amount of c-myc and ornithine decarboxylase mRNA are not evident, while the level of the mRNA for glucose-regulated protein GRP 78 increases later, concurrent with the onset of the acute phase response to surgical trauma. Analysis of polysomal and nonpolysomal fractions from sucrose gradients indicates that in postischemic liver, hsp 70 and hsc 73 mRNA are rapidly engaged on light polysomal or nonpolysomal complexes and are later shifted to polysomes. Albumin mRNA displays the same behavior, indicating that hsp 70 mRNA are not preferentially translated and that increased transcription is the major mechanism for enhanced hsp synthesis in postischemic liver. Damage by active oxygen species, pressure overload, and derangements of protein synthesis is likely to include the causative factors of increased expression of c-fos and the hsp 70 gene family in postischemic reperfused liver.
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PMID:Reprogramming of gene expression in postischemic rat liver: induction of proto-oncogenes and hsp 70 gene family. 210 73

We studied the time course and molecular mechanisms of changes in brain polyamines and their rate-regulatory synthetic enzyme ornithine decarboxylase during reversible forebrain ischemia and recirculation in the gerbil. Bilateral carotid occlusion induced an acute (less than 2 minutes), transient increase in ornithine decarboxylase activity and putrescine level. After 15 minutes of ischemia, recirculation evoked an immediate (less than 1 minute) increase in ornithine decarboxylase activity and putrescine concentration that progressed over a 15-minute period. A small rise in spermidine and spermine also was observed. A secondary increase in ornithine decarboxylase activity and the levels of putrescine and spermidine commenced after 6 hours of recirculation. Pretreatment with a-difluoromethylornithine, a specific suicide inhibitor of ornithine decarboxylase, or MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, abolished all early and delayed increases in ornithine decarboxylase activity and polyamine levels. This is the first demonstration that both ischemia and postischemic recirculation evoke rapid, transient increases in the activity of ornithine decarboxylase and the levels of polyamines, most notably the ornithine decarboxylase product, putrescine. Our results indicate that N-methyl-D-aspartate receptor activation (by an ischemically induced elevation of extracellular glutamate) is responsible for initiating the early and the delayed stimulation of ornithine decarboxylase activity. Ornithine decarboxylase activation causes the rapid rise in the levels of putrescine and higher polyamines observed in the acute response to ischemia and the acute and delayed response to postischemic recirculation. These polyamine changes may be involved in the pathophysiology of Ca2+ entry and neuronal death after brain ischemia.
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PMID:Brain polyamines are controlled by N-methyl-D-aspartate receptors during ischemia and recirculation. 214 83

In this study, we determined whether the persistency of cardiac hypertrophy after chronic vasodilation therapy with minoxidil (minox) was associated with functional or metabolic alterations in hypertensive rat hearts before, during and after an ischemic insult. In addition, we investigated the effects of the simultaneous administration of difluoromethylornithine (dfmo), a substance that could block hypertrophy by a direct inhibition of protein synthesis. Four groups of male Wistar rats were prepared: 1) normotensive controls (n = 8), 2) untreated renovascular hypertensive rats (HT, n = 15), 3) hypertensives treated with minox (8 mg/kg, n = 19), 4) hypertensives treated with minox and dfmo (1.7 g/kg, n = 20). After 21 days of treatment, the animals were sacrificed. In a small number of hearts, ornithine decarboxylase (ODC) activity was assayed in order to verify that dfmo, which is a suicide inhibitor of ODC, had effectively interrupted the polyamines pathway. The other hearts were prepared for retrograde perfusion at 35 degrees C and at constant flow (10 ml/min x g). Cardiac function was monitored via the balloon inserted in the left ventricle (LV) and the following protocol was applied: a) baseline period (24 min), b) ischemia (24 min), c) recovery (36 min). Finally, the hearts were weighed and LV wall thickness and inner radius were measured. Blood pressure was maintained near normotension in the two treated groups. Mean systolic pressure (in mmHg) was 145 +/- 4 with minox and 144 +/- 3 with minox + dfmo versus 181 +/- 4 in the HT group (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of long-term administration of vasodilators and "antitrophic" agents on the structure and function of the heart in hypertensive rats]. 214 71

An increase in the activity of the enzyme ornithine decarboxylase has been shown to be associated with ischemia and other lesions of the nervous system. We have previously characterized the induction of ornithine decarboxylase in cerebral cortex following excitotoxin lesion of the nucleus basalis and have shown it to be sensitive to treatment with MK-801 up to 4 hours after the lesion and to be associated with an early increase in ornithine decarboxylase mRNA. In this study, we have used this model to investigate the effect of dihydropyridines on this response to lesion. Injection of 1 micrograms kainate into the nucleus basalis causes a large increase in ornithine decarboxylase activity that is maximal at 8 hours (292 pmol/mg/hr) when there is a 200-fold increase in ornithine decarboxylase activity compared with unoperated control animals (1.4 pmol/mg/hr). Treatment of animals with nimodipine either 5 minutes before or 60 minutes after lesion did not affect the maximal ornithine decarboxylase response at 8 hours. However, repeated injections (four of nimodipine, 10 mg/kg) significantly (p less than 0.001) attenuated the response to lesion by 75%. Injections were given 5 minutes before lesion and at 1.0, 3.5, and 6.0 hours after lesion. The efficacy of this treatment regimen indicated that maintaining a blockade of dihydropyridine-sensitive channels over this period was necessary to attenuate this induction of ornithine decarboxylase. To investigate the critical period over which dihydropyridines might be effective, their action at the earlier time point of 4 hours was tested where a significant induction of ornithine decarboxylase occurs (60 pmol/mg/hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of neurotoxin-induced ornithine decarboxylase activity in rat cerebral cortex by nimodipine. A potential neuroprotective mechanism. 226 Jan 56

Reversible cerebral ischemia was produced in anesthetized Mongolian gerbils by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 8 or 24 h. Treated animals received a single intraperitoneal injection of pentobarbital (50 mg/kg) immediately after the aneurysm clips were removed. At the end of the experiments, animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, lateral striatum, CA1 subfield of the hippocampus, thalamus, and cerebellum for measuring ornithine decarboxylase (ODC) activity and putrescine levels. In addition, 20-microns-thick coronal tissue sections were taken from the level of the striatum and stained with hematoxylin/eosin for evaluating the extent of ischemic neuronal necrosis in the lateral striatum. In control animals ODC activity and putrescine levels amounted, respectively, to 0.32 +/- 0.03 nmol/g/h and 10.2 +/- 0.5 nmol/g in the cerebral cortex; 0.34 +/- 0.02 nmol/g/h and 12.8 +/- 0.5 nmol/g in the lateral striatum; 0.58 +/- 0.05 nmol/g/h and 10.5 +/- 0.7 nmol/g in the hippocampal CA1 subfield; 0.35 +/- 0.01 nmol/g/h and 9.8 +/- 0.4 nmol/g in the thalamus; and 0.25 +/- 0.01 nmol/g/h and 8.3 +/- 0.6 nmol/g in the cerebellum. After 5 min cerebral ischemia and 8 h recirculation, a significant 7- to 16-fold increase in ODC activity was observed in all forebrain structures studied. Following 24 h recirculation, ODC activity normalized in the cortex, striatum, and thalamus but was still significantly above control values in the hippocampal CA1 subfield.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ornithine decarboxylase activity and putrescine levels in reversible cerebral ischemia of Mongolian gerbils: effect of barbiturate. 230 40

The effects of a continuous 16-day gestational exposure to nicotine on brain development were examined in the offspring of dams who received a minipump implant on the 4th day of gestation. Maternal viability was unaffected and weight gain was only reduced slightly, but nearly half the dams failed to give birth; dams delivering pups had normal litter sizes. Examination of fetal macromolecules on the 18th day of gestation revealed specific deficits in cell number (DNA) in developing brain tissue as opposed to the rest of the fetus, accompanied by parallel shortfalls in other macromolecules (RNA, protein). After birth, brain development in the nicotine-exposed animals showed persistent abnormalities in the timing of maturational events, with elevated levels of ornithine decarboxylase (an enzymatic marker related to cellular maturation) detectable in all brain regions. Subsequent effects on macromolecules were highly selective regionally, with clear distinctions between areas in which neuronal replication occurs relatively late (cerebellum) compared to early-developing regions (midbrain plus brainstem). Differences apparent between the effects of infused maternal nicotine and those noted previously in studies with nicotine injections indicate that the drug does exert primary effects on developing neural tissues, but that other factors associated with the injection route (such as hypoxia and ischemia consequent to acute effects of nicotine) can interact with the drug to influence brain cell maturation.
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PMID:Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps. 243 31

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development. 290 81


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