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)

Adult rhesus monkeys were subjected to complete cerebral ischemia for one hour and subsequent recirculation for up to 24 h. Animals with signs of functional recovery (e.g. spontaneous EEG activity) exhibited a partial replenishment of cellular energy sources (ATP, phosphocreatine) and a progressive normalization of cerebral lactate levels. Glucose and pyruvate concentrations showed a transient increase over control values during the early stages of postischemic recirculation. Monkeys without functional recovery lacked a significant resynthesis of energy-rich compounds; adenine nucleotides continued to decrease and lactate concentrations were higher than in animals subjected to ischemia without recirculation. Cerebral polysome profiles remained unaltered during the ischemic period but in all animals a marked disaggregation of polyribosomes with a concomitant increase in ribosomal subunits occurred after the onset of recirculation. In monkeys with indications of functional recovery these changes were reversible but a normal polysome profile was only observed after 24 h of recirculation. The results obtained indicate a postischemic depression of protein synthesis due to an inhibition of peptide chain initiation. After recirculation of the brain for 3-6 h there was evidence for an induction of enzymes involved in polyamine synthesis (ornithine decarboxylase and S-adenosylmethionine decarboxylase). No changes in the activity of these enzymes were observed at the end of the ischemic period, indicating that during complete cerebral ischemia not only the synthesis but also the catabolism of proteins is inhibited.
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PMID:Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. 115 69

Biosynthesis of the polyamines spermidine and spermine and their precursor putrescine is controlled by the activity of the two key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). In the adult brain, polyamine synthesis is activated by a variety of physiological and pathological stimuli, resulting most prominently in an increase in ODC activity and putrescine levels. The sharp rise in putrescine levels observed following severe cellular stress is most probably the result of an increase in ODC activity and decrease in SAMDC activity or an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Spermidine and spermine levels are usually less affected by stress and are reduced in severely injured areas. Changes of polyamine synthesis and metabolism are most pronounced in those pathological conditions that induce cell injury, such as severe metabolic stress, exposure to neurotoxins or seizure. Putrescine levels correlate closely with the density of cell necrosis. Because of the close relationship between the extent of post-stress changes in polyamine metabolism and density of cellular injury, it has been suggested that polyamines play a role in the manifestation of structural defects. Four different mechanisms of polyamine-dependent cell injury are plausible: (1) an overactivation of calcium fluxes and neurotransmitter release in areas with an overshoot in putrescine formation; (2) disturbances of the calcium homeostasis resulting from an impairment of the calcium buffering capacity of mitochondria in regions in which spermine levels are reduced; (3) an overactivation of the NMDA receptor complex caused by a release of polyamines into the extracellular space during ischemia or after ischemia and prolonged recirculation in the tissue surrounding severely damaged areas; (4) an overproduction of hydrogen peroxide resulting from an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Insofar as a sharp activation of polyamine synthesis is a common response to a variety of physiological and pathological stimuli, studying stress-induced changes in polyamine synthesis and metabolism may help to elucidate the molecular mechanisms involved in the development of cell injury induced by severe stress.
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PMID:Polyamine metabolism in different pathological states of the brain. 135 85

Interest in ornithine decarboxylase (ODC) and the therapeutic effects of its inhibition with the consequent depletion of polyamine biosynthesis has been widespread since the late 1970s and 1980s. This review covers new information about the properties of ODC, recent findings with ODC inhibitors and a discussion of the mechanism of inactivation of ODC by eflornithine. Recent in vivo therapeutic approaches of ODC inhibition are also discussed including: cancer and cancer chemoprevention; autoimmune diseases; polyamines and the blood-brain barrier, ischemia and hyperplasia; the NMDA receptor and modulation by polyamines; hearing loss; African trypanosomiasis; Pneumocystis carinii pneumonia and Cryptosporidium in AIDS; and other infectious diseases/organisms.
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PMID:Ornithine decarboxylase as an enzyme target for therapy. 143 32

Mongolian gerbils were anesthetized with halothane and forebrain ischemia was induced by occluding both common carotid arteries. After 2, 4, 6, 8, or 10 min of vascular occlusion clips were removed and animals allowed to recover for 8 or 24 h. At the end of the experiments animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, striatum, hippocampus, and thalamus for determination of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activity by measurement of the release of 14CO2 from [14C]ornithine and S-[14C]adenosylmethionine, respectively. A transient increase in ODC activity was found after 8 h of recirculation following cerebral ischemia in all brain structures studied. ODC activity was significantly increased after 8 h of recirculation in the hippocampus of animals subjected to 4 min of ischemia, in the cortex and striatum after 6 min of ischemia, and in the thalamus after 8 min of vascular occlusion. ODC activity had already reached a plateau in the hippocampus after 4 min of vascular occlusion and in the cortex, striatum, and thalamus after 8 min, since there is no further increase in activity even after 10 min of ischemia. After cerebral ischemia and 24 h of recirculation ODC activity returned to control levels throughout the forebrain regardless of the duration of ischemia. SAMDC activity was significantly reduced after 8 h of recirculation following 4 to 10 min of ischemia in the cortex and 8 min of ischemia in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase in transient cerebral ischemia: relationship to the duration of vascular occlusion. 149 93

Synthesis of the polyamines putrescine, spermidine, and spermine is controlled by the activity of the key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). Beside their function in cellular growth processes, polyamines and particularly putrescine play a role in calcium-related events at the cell membrane, coupling an extracellular stimulus to an intracellular response (second messenger-like reactions), modulate the calcium-buffering capacity of mitochondria (spermine), and, if present in the extracellular compartment, modulate the activity of the N-methyl-D-aspartate receptor (spermidine and spermine). Reversible cerebral ischemia triggers pathological disturbances in polyamine metabolism that are characterized by a sharp increase in ODC synthesis, even in the most vulnerable hippocampal CA1 subfield in which overall protein synthesis is severely depressed at the same time, and a marked suppression of SAMDC synthesis in parallel with the inhibition of overall protein synthesis. ODC immunohistochemistry has revealed that the observed changes are neuronal responses to reversible ischemia. These changes in enzyme activities result in an overshoot in the formation of putrescine, the product of ODC activity. Spermine levels are significantly reduced in vulnerable brain structures after prolonged recirculation. In addition, evidence is accumulating that polyamines may be released from the cell during ischemia and after prolonged recirculation at a time when cell necrosis is apparent. This review will summarize the major features of ischemia-induced disturbances in polyamine metabolism and the possible consequences for the cells involved, taking into account that the underlying changes may be indicative of either the activation of a recovery process of neurons from the metabolic stress produced by reversible ischemia or pathological disturbances resulting in the manifestation of neuronal necrosis. Elucidating the mechanisms responsible for the postischemic disturbances in polyamine metabolism may lead to a better understanding of the molecular mechanisms involved in the development of neuronal necrosis after different pathological stimuli.
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PMID:Polyamine metabolism in reversible cerebral ischemia. 156 52

Anesthetized Mongolian gerbils were subjected to 5-min ischemia and 8 h of recirculation. Vibratom sections were taken for studying changes in ornithine decarboxylase (ODC) immunoreactivity using an antiserum to ODC, and tissue samples were taken for measuring ODC activity. After 5-min ischemia and 8-h recirculation ODC activity increased 11.5-, 5.9-, and 7.9-fold in the cerebral cortex, striatum and hippocampus, respectively (P less than or equal to 0.05 to 0.01). In the cortex, striatum and hippocampus of control animals immunoreactivity was low but clearly above the detection limit. The reaction was confined to neurons. After 5-min ischemia and 8-h recirculation a sharp increase in immunoreactivity was observed confined to neurons, indicating that the postischemic activation of polyamine metabolism is a neuronal response to ischemia. The immunoreactivity was markedly increased in the perinuclear cytoplasm and the dendrites. In the striatum the density of neurons exhibiting a sharp increase in immunoreactivity was more pronounced in the lateral than in the ventral part. In the hippocampus a strong reaction was present in all subfields but the CA1 subfield was particularly affected. The present study demonstrates for the first time that biosynthesis of a protein is markedly activated during the first 24 h of recirculation after 5-min cerebral ischemia of gerbils even in the vulnerable CA1 subfield, in which the overall protein synthesis is sharply reduced at the same time. Studying polyamine metabolism after ischemia may, thus, provide new information about the basic molecular mechanisms responsible for the altered gene expression after metabolic stress.
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PMID:Ornithine decarboxylase in reversible cerebral ischemia: an immunohistochemical study. 172 36

The aim of this experiment was to demonstrate whether histamine and histidine decarboxylase (HDC) contribute to mucosal repair in small intestine subjected to ischemia-reperfusion (I/R). The superior mesenteric artery was occluded for 15 min followed by reperfusion. In jejunal mucosa, histamine content and HDC activity increased after I/R. Histamine output in mesenteric lymph was also elevated after I/R. These increases in HDC activity, and mucosal and lymph histamine levels were suppressed by pretreatment of alpha-fluoromethylhistidine (alpha-FMH), a suicide inhibitor of HDC. alpha-FMH also attenuated the increase of ornithine decarboxylase (ODC) activity normally observed after I/R. Transport of dietary lipid into lymph markedly decreased at 24 h after I/R, yet it was restored to normal at 48 h after I/R. alpha-FMH inhibitor led to a sustained deficit in lipid transport at 48 h after I/R. This sustained functional impairment in alpha-FMH treated animals was associated with blunted responses of HDC activity and histamine content to I/R. Our results suggest that histamine and HDC contribute to the restoration in mucosal function observed at 48 h after I/R. This response may be related, at least in part, to stimulation of ODC activity by histamine.
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PMID:Histamine and histidine decarboxylase are correlated with mucosal repair in rat small intestine after ischemia-reperfusion. 172 65

Exposure to cocaine during development has been shown to cause structural and functional alterations in the nervous system. In the current study, the mechanisms underlying these effects were examined in neonatal rats through measurement of ornithine decarboxylase activity, a key regulatory enzyme in the control of neural cell differentiation. Animals were given cocaine (30 mg/kg SC) and ornithine decarboxylase measured 1 and 4 h later in midbrain + brainstem, cerebral cortex and cerebellum. Cocaine caused inhibition of ornithine decarboxylase activity that was not secondary to local anesthesia, as lidocaine was ineffective. The effect of cocaine was independent of direct central actions, as introduction of the drug into the central compartment via intracisternal injection failed to inhibit ornithine decarboxylase. In contrast, prevention of cocaine-induced ischemia by peripheral alpha-adrenergic blockade (phenoxybenzamine) reversed the ornithine decarboxylase inhibition caused by cocaine, and actually unmasked potential stimulatory actions. These data indicate that cocaine-induced ischemia is a major contributor to the net effect of the drug on central nervous system cellular development.
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PMID:Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat. 178 62

Nicotine exposure during development alters central nervous system structure and function. In the current study, we examined the acute effects of nicotine (3 mg/kg) on developing rat brain by monitoring ornithine decarboxylase (ODC), a marker for perturbed cell development; ODC controls polyamine biosynthesis and thus regulates cell differentiation. Three brain regions were selected that differ both in their timetables for maturation and in nicotinic receptor concentrations: midbrain + brainstem (earliest development, highest receptor concentration), forebrain (intermediate profiles) and cerebellum (latest development and lowest receptor concentration). Nicotine caused stimulation of ODC within 1 h after drug administration, an effect that displayed both age- and region-dependence corresponding to the development of central nicotinic receptors: effects appeared earliest and were largest in magnitude in midbrain + brainstem and forebrain, and appeared last and with smaller magnitude in the cerebellum. Central receptor involvement was confirmed at 8 days postpartum by demonstrating desensitization of the response after repeated nicotine administration, and by evoking equivalent effects with direct introduction of a small dose of nicotine into the central nervous system. Later in development, acute stimulation of ODC by nicotine became less selective, reflecting secondary actions mediated through systemic hypoxia caused by the drug; this conclusion was confirmed by the absence of desensitization after repeated nicotine administration, and by the failure of centrally administered nicotine to evoke a full stimulatory response. Nicotine-induced ischemia did not contribute to stimulation of ODC seen at the 1 h time point: pretreatment with chlorisondamine, a ganglionic nicotinic antagonist, failed to alter the central stimulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute stimulation of ornithine decarboxylase in neonatal rat brain regions by nicotine: a central receptor-mediated process? 179 Jun

Polyamine metabolism was studied in rat brains subjected to 30 min transient cerebral ischemia by measuring the activity of the key enzyme ornithine decarboxylase (ODC) and levels of the polyamines putrescine, spermidine and spermine. A transient increase in ODC activity was apparent after 4 h of recirculation in the ipsilateral cortex and striatum (P less than 0.05). Putrescine levels were significantly increased in the ipsilateral striatum after 4 h of recirculation, and after 24 h of recirculation in both the ipsilateral cortex and striatum. During ischemia spermidine levels were significantly reduced in the ipsilateral hemisphere and spermine levels in the ipsilateral cortex. It is suggested that during ischemia polyamines are released from neurons into the extracellular compartment and cleared into the blood.
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PMID:Polyamine metabolism in transient focal ischemia of rat brain. 181 56


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