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)

The beneficial effects of alpha-difluoromethylornithine (DFMO) were assessed in a model of peripheral ischemia. DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the production of polyamines. A 7 x 7 cm rat abdominal skin flap was surgically raised based on two inferior epigastric nerve, artery, and vein pedicles. One of the pedicles was then ligated and the skin was sutured back in place. Necrosis of skin was assessed 2 and 7 days after surgery. The rats were divided into four groups: control, DFMO, DFMO + polyamines, and polyamines alone. DFMO was administered in drinking water at 0.2%. Polyamines (putrescine, spermidine, and spermine) were each administered by daily i.p. injection at a dose of 10 mg/kg. The percentage of necrosis of the area of skin at risk in controls was 65 +/- 2% (mean +/- SEM). Necrosis was significantly reduced with DFMO (19 +/- 1%), with DFMO plus polyamines (37 +/- 3%), or with polyamines alone (41 +/- 2%). Protein synthesis and ornithine decarboxylase activity in the skin were both significantly decreased by DFMO. These studies demonstrate that DFMO protects skin from ischemic damage at least in part through actions on polyamine metabolism.
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PMID:Reduced cell death in skin flaps in rats treated with difluoromethylornithine. 311 14

Severe forebrain ischemia was produced in rats by occluding both carotid and vertebral arteries. Following 30 min ischemia brains were recirculated for 8 or 24 h. Twelve animals subjected to 8 or 24 h recirculation (n = 6, each group) were given alpha-difluoromethylornithine (DFMO; injected intraperitoneally) immediately before recirculation. At the end of the experiments brains were frozen and samples were taken from the cerebellum, cortex, caudatoputamen and hippocampus. Samples from the left hemisphere were used for measuring ornithine decarboxylase (ODC) activity, and those from the right hemisphere for determining putrescine profiles. During recirculation ODC activity increased markedly in all brain structures, the most pronounced change being in the caudatoputamen after 8 h recirculation. Putrescine increased drastically after 8 h and even more after 24 h recirculation. DFMO-treatment significantly reduced ODC activity after 8 h recirculation and following 24 h recirculation. Putrescine, however, was significantly reduced following 24 h but not after 8 h recirculation. The discrepancy between reduction in ODC activity and putrescine levels in DFMO-treated animals was most prominent in the hippocampus after 8 h recirculation: here DFMO reduced ODC activity to control values without affecting putrescine levels. The results suggest that the observed overshoot in putrescine formation following ischemia is only partly caused by activation of ODC.
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PMID:Polyamine metabolism in reversible cerebral ischemia: effect of alpha-difluoromethylornithine. 313 21

Ornithine decarboxylase, rate-limiting in polyamine formation, has been found to be necessary for the development of vasogenic edema after cryogenic cerebral injury and is postulated to be of importance in late ischemic brain edema formation. Ornithine decarboxylase activity and accompanying edema was studied after transient cerebral ischemia in Mongolian gerbils. Bilateral carotid artery occlusion was utilized to produce dense forebrain ischemia. After 4 h of reperfusion a significant elevation in ornithine decarboxylase activity was present (72.5 +/- 24.7 vs 8.5 +/- 2 pmoles/mg protein/h, p less than 0.05). Immunohistochemical localization of ornithine decarboxylase indicated its presence in cortical neurons of ischemic gerbils. This was typically located in the perinuclear cytoplasm and extended into proximal dendrites. Nonischemic animals did not contain ornithine decarboxylase immunoreactivity. These studies show the presence and location of ornithine decarboxylase in cerebral tissue subjected to transient ischemia. The increase in this marker of polyamine activity paralleled previous studies in this model of cerebral edema formation and reperfusion deficit in blood flow and evoked potential, suggesting that ornithine decarboxylase is a marker for and may be associated with those late metabolic events leading to progressive functional deterioration after incomplete cerebral ischemia.
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PMID:Ornithine decarboxylase activity and immunohistochemical location in postischemic brain. 319 49

Reversible cerebral ischemia was produced in Mongolian gerbils by occluding both common carotid arteries. Following 5 min of ischemia brains were recirculated for 8, 24, or 96 hr. At the end of the experiments tissue samples were taken from the cerebral cortex and CA1 subfield of the hippocampus for measuring putrescine content and ornithine decarboxylase (ODC) activity. In 5 of 10 animals subjected to 96 hr of recirculation pentobarbital (50 mg/kg) was injected during early recirculation, and the density of ischemic cell damage was determined in the CA1 subfield of the hippocampus in treated and untreated animals. Reversible cerebral ischemia induced a drastic increase in ODC activity after 8 hr of recirculation (about 14-fold in the cortex and 7-fold in the hippocampus), which was markedly reduced following 24 hr of recirculation. Putrescine, in contrast, was high following 8 hr of recirculation and increased even further from 8 to 24 hr of recirculation. Postischemic pentobarbital treatment of animals significantly reduced both the increase in putrescine and the density of ischemic cell damage in the hippocampus. The results are discussed in view of the known activities of putrescine.
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PMID:Polyamine metabolism in reversible cerebral ischemia of Mongolian gerbils. 324 7

Renal damage caused by cyclosporine (CsA) has been documented. Clinical experiences have shown preservation injury further potentiates CsA nephrotoxicity. This study examined the mechanism of nephrotoxicity defined by changes in protein synthesis, DNA synthesis, and ornithine decarboxylase activity in an in vitro model. Initial results showed that CsA inhibited dog kidney epithelium cell (MDCK) replication at a dose of 200 ng after 24 hr (P less than .01) and 100 ng after 48 hr (P less than .01). Protein synthesis was inhibited with 100 ng after 24 and 48 hr (P less than .01). There was a reduction in ODC activity with 200 ng CsA (P less than .05). Methods for simulating transplant-related injuries were then developed. Under ischemic conditions, 18 hr were required before a synergistic effect with CsA produced a reduction in replication (P less than .05). Incubation of MDCK cells in preservative solution at 4 degrees C under hypoxic conditions resulted in a time-dependent reduction in synthetic and replicative capacity that plateaued at 24 hr (P less than .01). The next step was to simulate the clinical situation by combining treatments. MDCK cells were incubated for 24 hr in preservative solution under hypoxic conditions at 4 degrees C, and then CsA was added at defined intervals. The addition of CsA before 24 hr resulted in a significant decrease in cell replication (P less than .05) compared with CsA addition after 48 hr. Similar results were obtained with cells incubated for 48 hr in preservative solution with hypoxia. These data suggest that renal injury from ischemia and cold storage requires a period of cellular repair and replication. Administration of CsA before this period results in further renal injury. Our analysis offers an explanation of CsA nephrotoxicity seen in the human situation and, therefore, may provide a model for studying human nephrotoxicity.
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PMID:An in vitro model for analyzing the nephrotoxicity of cyclosporine and preservation injury. 355 62

Putrescine, spermidine, and spermine levels were measured in the cortex, caudoputamen, and hippocampus of rats during 30 min of severe forebrain ischemia (induced by occlusion of both carotid and vertebral arteries) and subsequent recirculation. During ischemia, polyamine levels did not change significantly. During postischemic recirculation, however, putrescine levels dramatically increased whereas those of spermine and spermidine did not change, with the exception of the severely damaged caudoputamen, where the concentration declined after 24 h. The increase of putrescine is explained by postischemic activation of ornithine decarboxylase and inhibition of S-adenosylmethionine decarboxylase. It is suggested that the accumulation of putrescine during postischemic recirculation may be responsible for the delayed neuronal death occurring after ischemia.
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PMID:Polyamine changes in reversible cerebral ischemia. 358 39

This study examines the pathophysiology of stroke secondary to focal cerebral ischemia. The interaction of arachidonic acid metabolites and polyamines, a class of ubiquitous ornithine-derived molecules with important membrane effects on edema, Ca++-dependent endocytosis, platelet function, and prostaglandin (PG) formation, are correlated with regional changes in H2 clearance, cerebral blood flow (rCBF), ischemic edema, and somatosensory evoked responses (SSERs) after middle cerebral artery (MCA) occlusion. Thirty cats were studied up to 3 hours before and 6 hours after right MCA occlusion. Four areas of brain showing different levels of perfusion after MCA occlusion were sampled for tissue levels of PGs: 6-keto-PGF1 alpha, PGE2, and as well as thromboxane B2 (TXB2), ornithine decarboxylase activity (ODC) (a measure of polyamine activity) and gravimetric determination of cerebral edema. After right MCA occlusion, right hemisphere SSER amplitude decreased and interpeak latency increased markedly. rCBF was distributed into zones of dense, partial, and no ischemia ranging from 12.6 to 59.4 ml/100 g/minute. Ischemic edema was distributed inversely to rCBF and was increased in areas of dense ischemia (85.2 +/- 0.5%) and ischemia (82.7 +/- 0.7%), but not in partially ischemic or control areas. 6-Keto-PGF1 alpha (1257.3 pg/mg), PGE2 (1628.5 pg/mg), and TXB2 (1572.8 pg/mg) were all significantly (P less than 0.05) increased in areas of partial ischemia that had not yet developed edema. ODC levels were significantly elevated (3812 pmole/g/hour, P less than 0.05) and increased with time in areas of slightly denser ischemia that showed an intermediate increase in edema, but not the presence of infarction. This is the first demonstration that ODC, the rate-limiting enzyme for polyamine synthesis, is stimulated by cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyamine and prostaglandin markers in focal cerebral ischemia. 386 30

In the isolated perfused rat hearts, the activity of tissue ornithine decarboxylase gradually decreases over 90 min. In contrast, the activity of S-adenosylmethionine decarboxylase, lactate dehydrogenase, and glutamate-oxalacetate transaminase stays unchanged after a small decrease during the first 10 min. Ornithine decarboxylase is released from the perfused heart under conditions in which neither the lower molecular weight S-adenosylmethionine decarboxylase nor polyamines leak out. Ten minutes of ischaemia did not change the rate of release of ornithine decarboxylase. Ischaemia followed by reperfusion (20 min) increased release of ornithine decarboxylase.
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PMID:Ornithine decarboxylase in perfused rat heart. 395 94

RU 24722, a compound selected for its protective effect against cerebral anoxia and ischemia in rats, induced a dose-dependent increase in brain ornithine decarboxylase (ODC), a rate limiting enzyme in the biosynthesis of polyamines. This action already 2 hr after injection, increased at 4 and 6 hr and ODC activity returned to pretreatment levels at 16 hr. Since it has been shown previously that glucocorticoids stimulate brain ODC, it was considered necessary to know if corticosterone could play a role in the action of RU 24722. This compound increased serum corticosterone levels 1 hr after injection, its effect being nil at 4 hr. Nevertheless, the effect of RU 24722 on brain ODC does not appear to be entirely dependent on the increase of serum corticosterone. the delays needed to obtain a stimulation of the enzyme by the steroid are longer (6 hr) than those necessary to observe the action of the drug (2 hr)on brain ODC. Furthermore, RU 24722 increased brain ODC even in adrenalectomized animals. In order to get an insight on the interaction of RU 24722 with putative transmitters, we have studied the effect of the compound on brain ODC in the presence of different pharmacological agents. Experiments performed using noradrenergic agonists and antagonits suggest that the action of RU 24722 on brain ODC is due to the blockade of inhibitory post-synaptic alpha-2 adrenoceptors. We have studied the action of other compounds, used for the treatment of senile cerebral insufficiency: codergocrine, dihydroergocristine, dihydroergocryptine, dihydroergocornine, dihydroergocristine and piribedil increased rat brain ODC; vincamine, piracetam and nicergoline were devoid of any action.
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PMID:In vivo effect of RU 24722 and drugs used for the treatment on senile cerebral insufficiency on rat brain ornithine decarboxylase. 399 51

In liver cells recovering from reversible ischemia the increase in RNA synthesis by isolated nuclei is preceded by activation of ornithine decarboxylase, leading in turn to an increase in putrescine concentration. Treatment of the animals with 1,3-diaminopropane and putrescine prevents ornithine decarboxylase activation but does not hinder the enhancement of RNA synthesis in post-ischemic liver nuclei; therefore, ornithine decarboxylase activation does not seem to be a necessary prerequisite for the increase in RNA synthesis. Hypophysectomy does not prevent the post-ischemic increases of ornithine decarboxylase and RNA synthesis; but pre-treatment of the animals with cycloheximide--which has a dual effect on the activity of ornithine decarboxylase--abolishes the post-ischemic enhancement of RNA synthesis. In contrast with regenerating liver, changes in ornithine decarboxylase activity and putrescine concentrations in reversible ischemia are not associated to changes in S-adenosylmethionine decarboxylase activity and in spermine and spermidine concentrations that seem to be characteristic of tissues where increases in RNA synthesis are followed by DNA synthesis and cell multiplication.
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PMID:Relationships between polyamine metabolism and RNA synthesis in post-ischemic liver cell repair. 615 62


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