Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyamines positively modulate the activity of the N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors. The concentration of polyamines in the brain increases in certain pathological conditions, such as ischemia and brain trauma, and these compounds have been postulated to play a role in excitotoxic neuronal death. In primary cultures of rat cerebellar granule neurons, exogenous application of the polyamines spermidine and spermine (but not putrescine) potentiated the delayed neurotoxicity elicited by NMDA receptor stimulation with glutamate. Furthermore, both toxic and nontoxic concentrations of glutamate stimulated the activity of ornithine decarboxylase (ODC)--the key regulatory enzyme in polyamine synthesis--and increased the concentration of ODC mRNA in cerebellar granule neurons but not in glial cells. Glutamate-induced ODC activation but not neurotoxicity was blocked by the ODC inhibitor difluoromethylornithine. Thus, high extracellular polyamine concentrations potentiate glutamate-triggered neuronal death, but the glutamate-induced increase in neuronal ODC activity may not play a determinant role in the cascade of intracellular events responsible for delayed excitotoxicity.
 ...
PMID:Induction of ornithine decarboxylase by N-methyl-D-aspartate receptor activation is unrelated to potentiation of glutamate excitotoxicity by polyamines in cerebellar granule neurons. 809 73

We evaluated the effects on cerebral ischemia of a treatment with fructose-1,6-bisphosphate, a compound known to possess protective effects on acute ischemic injury in a variety of different tissues. We investigated the ability of the compound, administered either 15 minutes before or 15 minutes after the ischemic insult, in reducing the ischemia-induced changes in polyamine brain levels. The experiments were performed in adult, chloral hydrate-anesthetized Mongolian gerbils that underwent a 15 minutes ligation of the common carotid arteries followed by recirculation. Animals were sacrificed 1, 8 and 24 hours and immediately after the release of the occlusion. Polyamine brain levels were not modified during ischemia. Putrescine began to increase after eight hours from the release of the occlusion and we found it significantly increased after 24 hours in the hippocampus and striatum. We did not detect any significant changes in spermidine brain levels either during ischemia or during recirculation. Conversely, spermine appeared to decrease in the hippocampus while it did not show changes in striatum and medulla-pons. The activity of ornithine decarboxylase, a key enzyme in the biosynthesis of polyamines, resulted enhanced at the end of the ischemic period in all the brain regions tested and showed a peak at eight hours of recirculation in striatum and hippocampus whereas returned to control values in the medulla-pons. Fructose-1,6-bisphosphate significantly reduced the ischemia induced changes in polyamine brain content when administered before the ischemic insult while did not show protective properties when administered post-ischemically.
 ...
PMID:Effects of fructose-1,6-bisphosphate on brain polyamine biosynthesis in a model of transient cerebral ischemia. 815 42

We have followed the time-course of the morphological and functional recovery of intestinal mucosa after 90 min of mesenteric vascular occlusion. At the end of the ischemic period the villi were smashed, but crypts were preserved. Microvillous hydrolase activities showed a dramatic drop when compared with sham-operated controls. Reperfusion was followed by an immediate upsurge of ornithine decarboxylase activity and a significant (p < 0.01) enhancement of putrescine and N1-acetyl-spermidine concentrations, while spermidine and spermine concentrations in mucosal cells decreased. This indicated that, both, de novo synthesis and degradation rates of the polyamines were increased. Treatment with alpha-difluoromethyl-ornithine, a selective inactivator of ornithine decarboxylase prevented the accumulation of active enzyme, but did not prevent morphological healing. It delayed however the recovery of sucrase and aminopeptidase-specific activities. Our results suggest that in addition to de novo synthesis, other sources of polyamines are mobilized to an extent that growth at a normal rate is supported. This indicates that the presence of active ornithine decarboxylase enzyme is not a prerequisite for the restitution of intestinal integrity after ischemia. We suggest that in a situation of inadequate polyamine supply the restoration of vital processes (mucosal regeneration) has priority over the restoration of specific functions.
 ...
PMID:Polyamines and the recovery of intestinal morphology and function after ischemic damage in rats. 817 30

Brain polyamines have been associated with posttraumatic vasogenic edema and blood-brain barrier (BBB) breakdown seen in some models of brain injury. We hypothesized that the inhibition of the enzyme responsible for polyamine production with the decarboxylase difluoromethylornithine (DFMO) may decrease BBB breakdown after a focal brain ischemic stroke. Thirty-two cats underwent 8 hours of middle cerebral artery occlusion and one of four treatments: sham operation (Sham), ischemia (Isc), ischemia/DFMO (Isc/DF), and ischemia/DFMO/putrescine (Isc/DF/PU). The regional brain specific gravity and the volume of Evans blue (EB) extravasation were measured at the time of death. The groups were monitored for temperature, heart rate, blood pressure, and arterial blood gases, and the values did not differ outside normal physiological ranges. EB results were expressed as the percentage of the hemisphere stained and showed the following: Sham, 2.23%; Isc, 32.8%; Isc/DF, 5.6%; Isc/DF/PU, 36.3%. As a measure of BBB, ischemia increased EB staining; DFMO pretreatment decreased the amount of EB staining to control levels; and the polyamine putrescine abolished the protective effect of DFMO (all significant at P = 0.05). DFMO pretreatment also resulted in a significant (P = 0.05) return to control values for specific gravity in the EB-stained regions (1.0328) of ischemic animals. This effect was present primarily in the white matter. Treatment with DFMO, an ornithine decarboxylase inhibitor, significantly decreased postischemic BBB breakdown and vasogenic edema in this model.
 ...
PMID:Difluoromethylornithine decreases postischemic brain edema and blood-brain barrier breakdown. 826 88

To examine the roles of histamine and diamine oxidase in the intestine after ischemia-reperfusion, we measured histamine content, diamine oxidase activity, and ornithine decarboxylase activity in rat intestinal mucosa 6 hr following various periods of ischemia. In addition, mortality rates of rats after various periods of ischemia were observed. The superior mesenteric artery was occluded for 15, 30, or 60 min. Ornithine decarboxylase activity increased in the 15-, 30-, and 60-min ischemic groups compared to the sham-operated control group. In the prolonged ischemic group (60-min ischemia), both histamine concentration and diamine oxidase activity in the mucosa decreased, contributing to an increase in circulating histamine. In the 60-min ischemic group, the mortality rate of rats was 25%, which was significantly larger than the control groups. Pretreatment with aminoguanidine, which suppressed diamine oxidase activity, increased the mortality rate. These results indicate that histamine released from the intestinal mucosa has a harmful effect on rats, and diamine oxidase activity plays an important role when the small intestine is subjected to prolonged period of ischemia.
 ...
PMID:Roles of histamine and diamine oxidase in mucosa of rat small intestine after ischemia-reperfusion. 832 82

Polyamines and ornithine decarboxylase, the polyamine biosynthetic enzyme, have been demonstrated to increase in the early phase of several types of brain lesion. However, their role in the pathogenesis of tissue damage is still debated. In the present paper the effects of treatments with alpha-difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase, have been investigated in a model of transient forebrain ischemia. Three treatment schedules were used: alpha-difluoromethylornithine treatment was either started 3 hr before and repeated 1 hr after the insult, or started at the time of the insult and continued for 3 or 7 days after post-ischemic reperfusion. The rats were sacrificed 4 hr, 7 or 40 days after reperfusion, respectively. The acute experiment demonstrated that alpha-difluoromethylornithine can reduce the increase of glial fibrillary acid protein immunoreactivity, an early marker of astroglial reaction, in ischemic striatum. Subchronic and chronic alpha-difluoromethylornithine treatments induced a worsening of the morphological outcome of the ischemic lesion. In caudate-putamen a trend for an increase of the area of neuronal loss was present after both treatments. In the hippocampal formation, a significant increase in the severity of neuronal lesion was observed in the mildly lesioned CA3 field. In addition, other alterations of lesioned tissue were observed in alpha-difluoromethylornithine-treated animals, including increases of non-neuronal cells at 7 and especially 40 days post-lesion in striatum and CA3 hippocampal field. In conclusion, present data indicate that ornithine decarboxylase activation after ischemic lesion is a crucial factor for survival of mildly lesioned neurons and proper tissue reaction to the ischemic lesion. The experiment on acute alpha-difluoromethylornithine treatment suggests that these effects may be, at least in part, related to putrescine-induced activation of astroglial cells in the early post-lesion period.
 ...
PMID:Effects of polyamine synthesis blockade on neuronal loss and astroglial reaction after transient forebrain ischemia. 832 99

In order to evaluate the systemic and neural factors on ornithine decarboxylase (ODC) activity of rat intestinal mucosa, ODC activity in duodenal mucosa, where blood flow did not decrease by superior mesenteric artery (SMA) occlusion, was compared to that of jejunal and ileal mucosa, where blood flow decreased to 90% of the initial value after SMA occlusion. Rats were allowed to recover after SMA occlusion before harvesting intestinal mucosa for measuring ODC activity. ODC activity in the jejunum and the ileum increased markedly 6 h after ischemia-reperfusion (I/R) and more than 72 h were required for ODC activity to return to normal. ODC activity in the duodenum did not change until 24 h after I/R, but the activity increased 48 h after I/R, and this increase continued for 2 days. Subdiaphragmatic vagotomy completely abolished the increase in ODC activity in the duodenum, whereas the same procedure had no influence on ODC activity in the jejunum or the ileum. These results indicate that a neural signal from the central nervous system via the efferent vagal nerve following I/R was an important factor in the increase in ODC activity of duodenal mucosa, where blood flow was not influenced by SMA occlusion.
 ...
PMID:Subdiaphragmatic vagotomy abolishes increase in ornithine decarboxylase activity of rat duodenal mucosa after ischemia-reperfusion in superior mesenteric artery. 837 23

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is induced in ischemic tissue and may mediate vasogenic edema and delayed neuronal death. We determined the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, on infarct size and ODC activity in a rat model of transient focal ischemia. DFMO blocked the ischemia-induced increase in ODC and significantly reduced infarct volumes by 57-45%, depending upon the treatment regimen. These studies suggest that polyamine metabolism plays a role in the development of cerebral infarction after focal ischemia and that DFMO may be useful in limiting injury after a stroke.
 ...
PMID:DFMO reduces cortical infarct volume after middle cerebral artery occlusion in the rat. 840 13

Current knowledge of liver regeneration after reduced liver transplantation is limited. Warm ischemia is one component of the reduced liver transplantation procedure that could have an impact on the regenerative response. To study this effect, we performed partial hepatectomy on male Long-Evans rats, with animals divided into four groups: group 1 underwent partial hepatectomy only; group 2 underwent partial hepatectomy and 40 min of ischemia; group 3 underwent partial hepatectomy, 40 min of ischemia and portocaval shunt surgery; and group 4 underwent partial hepatectomy and orthotopic autograft surgery. Group 5 consisted of sham-operated animals. Animals were killed 4, 24, 48, 72 and 96 hr after surgery. Thymidine kinase activity, mitotic index, a liver mass index and ornithine decarboxylase levels were used as parameters of liver regeneration. Aspartate transaminase was recorded. Maximal thymidine kinase and mitotic index were observed in group 1 animals at 24 hr. In groups 2, 3 and 4 maximal thymidine kinase activity and mitotic activity were observed 24 hr later at 48 hr. The magnitude of the peak response in these groups appeared to correlate with the duration of portal venous occlusion, with greatest increases occurring in those groups where portal stasis was most prolonged. The increase in liver mass for these groups was also delayed with respect to group 1 animals. The anticipated peak in ornithine decarboxylase levels was seen at 4 hr in group 1. The ornithine decarboxylase response in the other groups was disorganized, with delay of the recorded peaks.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Liver regeneration after hepatic ischemia and reduced liver autotransplantation in the rat. 842 25

Hepatic ischemia was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of the rat liver. Hepatic ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities in ischemic and nonischemic regions were increased and, respectively, peaked by 6 hr and 3 hr after 1 hr of hepatic ischemia. Hepatic putrescine contents in ischemic and nonischemic regions were increased and peaked by 6 hr. However, hepatic spermidine and spermine were not increased. an increase in ODC activity was also observed in the spleen and the kidney after 1 hr of hepatic ischemia. [3H]thymidine incorporation into DNA was observed in the liver and the spleen--however it was not observed in the kidney--after hepatic ischemia.
 ...
PMID:The effect of hepatic ischemia-reperfusion on polyamine metabolism in some organs of the rat. 843 75


<< Previous 1 2 3 4 5 6 7 8 Next >>