Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown that there is a highly significant difference between right and left ventricular ornithine decarboxylase activity. The left ventricle had a much higher activity compared with the right ventricle. A restricted diet caused a decrease in ornithine decarboxylase activity after 24 hr. Hypoxia caused a depression of the ornithine decarboxylase activity during the first 2 days of the experiment. In the hypertrophied right ventricle there was an initial decrease in ornithine decarboxylase after 24 hr and then a gradual increase in ornithine decarboxylase activity during the 7 days of the experiment. The increase in ornithine decarboxylase activity became significant when an increase in tissue weight became apparent.
 ...
PMID:The effects of hypoxia, hypertrophy, and diet on rat myocardial ornithine decarboxylase activity. 13 64

Heavy metal treatment (2 X 1 mg/kg per day) for 3, 5, and 7 days resulted in progressive augmentation in the incorporation of [14C]thymidine into hepatic DNA. In contrast with the observed enhancement in DNA synthesis, cadmium exposure tended to produce a decrease in the activity of hepatic ornithine decarboxylase (EC 4.1.1.17) at 1, 3, or 5 days with the lowest (34% of control values) enzymic activity seen after 7 days. A similar reduction in the activity of S-adenosylmethionine decarboxylase (EC 4.1.1.50) was observed in livers of rats treated with cadmium for 1-7 days. Subacute exposure to cadmium significantly lowered the hepatic levels of spermidine and spermine whereas the endogenous concentrated of putrescine remained unaltered. In addition to the observed effects on the biosynthesis of polyamines and DNA, heavy metal treatment produced stimulation of the hepatic adenylate cyclase (EC 4.6.1.1)--cyclic AMP system. Significant increases in the activity of hepatic adenylate cyclase and endogenous cyclic AMP levels were detected as early as 1 day and the observed alterations persisted during the entire 1-week period of cadmium exposure. The depression in polyamine formation was accompanied by enhanced DNA biosynthesis as well as stimulation in the adenylate cyclase-cyclic AMP system of rat liver.
 ...
PMID:Sequential changes in hepatic polyamine, deoxyribonucleic acid, and cyclic adenosine 3',5'-monophosphate metabolism after subacute exposure to cadmium in rats. 19 91

1. The activation of human peripheral blood lymphocytes by phytohaemagglutinin in vitro was accompanied by striking increases in the concentrations of the natural polyamines putrescine, spermidine and spermine. 2. The enhanced accumulation of polyamines could be almost totally abolished by dl-alpha-difluoromethylornithine, a newly discovered irreversible inhibitor of l-ornithine decarboxylase (EC 4.1.1.17), or by methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidene)dinitrilo]diguanidine}, an inhibitor of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50). The inhibition of polyamine accumulation was associated with a marked suppression of DNA synthesis, which was partially or totally reversed by low concentrations of exogenous putrescine, spermidine, spermine and cadaverine and by higher concentrations of 1,3-diaminopropane. 3. In contrast with some earlier studies, we found that methylglyoxal bis(guanylhydrazone), at concentrations that were sufficient to prevent polyamine accumulation, also caused a clear inhibition of protein synthesis in the activated lymphocytes. Similar results were obtained with difluoromethylornithine. The decrease in protein synthesis caused by both compounds preceded the impairment of DNA synthesis. The inhibition of protein synthesis by difluoromethylornithine was fully reversed by exogenous putrescine, spermidine and spermine, and that caused by methylglyoxal bis(guanylhydrazone) by spermidine and spermine. In further support of the idea that the inhibition of protein synthesis by these compounds was related to the polyamine depletion, we found that difluoromethylornithine caused a dose-dependent decrease in the incorporation of [(14)C]leucine into lymphocyte proteins which closely correlated with the decreased concentrations of cellular spermidine. 4. Difluoromethylornithine and methylglyoxal bis(guanylhydrazone) also elicited a variable depression in the incorporation of [(3)H]uridine and [(14)C]adenine into total RNA. The apparent turnover of lymphocyte RNA remained essentially unchanged in spite of severe polyamine depletion brought about by difluoromethylornithine. 5. The present results, as well as confirming the anti-proliferative action of the inhibitors of polyamine biosynthesis, suggest that polyamine depletion may interfere with reactions at different levels of gene expression.
 ...
PMID:Suppression of the formation of polyamines and macromolecules by DL-alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) in phytohaemagglutinin-activated human lymphocytes. 43 70

1. 1,3-Diaminopropane and some of its derivatives are potent inhibitors of ornithine decarboxylase (EC 4.1.1.17) in Ehrlich ascites cells grown in suspension culture. Among the amine derivatives tested, 1,3-diamino-2-propanol most effectively prevented any accumulation of spermidine and spermine in ascites cells when the proliferation was stimulated by diluting the cells with fresh medium. 2. The effectiveness of diaminopropanol in abolishing polyamine accumulation was primarily based on a rapid decay of ornithine decarboxylase activity following the exposure of the cells to the drug. 3. The mechanism of action of diaminopropanol on ornithine decarboxylase apparently involved a formation of macromolecular inhibitors or 'antizymes' to the enzyme. 4. Even though the inhibitory effect of 1,3-diaminopropane on polyamine accumulation approached that of diaminopropanol, the former compound only marginally inhibited the incorporation of [3H]thymidine into DNA and that of [14C]leucine into protein, in contrast to the marked depression of macromolecular synthesis produced by diaminopropanol. The apparent dissociation of polyamine depletion brought about by 1,3-diaminopropane from an antiproliferative action was apparently due to the fact that diaminopropane, unlike diaminopropanol, was partially capable of taking over the function of natural polyamines. 5. The inhibition of DNA and protein synthesis as well as the prevention of increase in cell number by diaminopropanol was closely associated with polyamine depletion and was fully comparable, as regards timing and magnitude, with that achieved with difluoromethylornithine. The antiproliferative effect of diaminopropanol, however, was only partly reversed by a simultaneous addition of putrescine (or spermidine) into the culture medium. The lack of a complete reversal of the action of diaminopropanol on cell growth by natural polyamines was apparently due to the fact that it was remarkably difficult or even impossible to increase intracellular polyamine concentrations by exogenous polyamines in the presence of diaminopropanol. Nevertheless, the diaminopropanol-induced arrest of growth was reversible as judged by a rapid increase in ornithine decarboxylase activity followed by restoration of DNA synthesis.
 ...
PMID:Inhibition of polyamine accumulation and cell proliferation by derivatives of diaminopropane in Ehrlich ascites cells grown in culture. 49 23

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.
 ...
PMID:Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. 115 69

Separation of neonates from their dam has been shown to evoke acutely a variety of biochemical responses, typified by depression of ornithine decarboxylase (ODC) activity. In the current study where rat pups were removed from their nursing dams for 6 h, ODC activities in the liver, heart, kidney and lung were markedly suppressed, but the enzyme in the brain was not altered during the early postnatal ages. These data suggest that the brain was protected from maternal separation insults, a homeostatic response mediated in part, by an increase of circulating corticosterone and glycogen mobilization from peripheral tissues, particularly the liver. In addition, we examined whether these responses were extended to pups who were subject to repeated episodes of maternal deprivation, and whether this stress paradigm might be associated with corresponding changes of cellular growth and maturation. Pups were removed from their dams for 6 h daily beginning at 4 days of age until weaning at 21 days. Plasma corticosterone levels of the deprived pups were elevated significantly at the end of each stress episode but returned to basal (control) levels subsequently. The repeating stress paradigm did not influence the magnitude of this hormonal response at the ensuing ages. Consistent with findings observed in the single episodes of stress, ODC activities in the peripheral tissues were significantly depressed in pups subject to repeated maternal deprivation, but the enzyme appeared to recover to control levels 18 h after each insult. In contrast, brain ODC activity did not exhibit any change throughout the period examined. Moreover, while ontogenetic gains of DNA and protein in the peripheral tissues of the deprived rats lagged slightly but consistently behind those of controls, these macromolecules in the brain were not affected appreciably. These results thus suggest that brain growth was, by and large, spared from insults associated with repeated maternal separation; but this stressful paradigm did produce marked, though reversible biochemical and physiological responses in the peripheral tissues of neonates, which cumulatively led to a lag of cellular development.
 ...
PMID:Repeated maternal separation in the neonatal rat: cellular mechanisms contributing to brain growth sparing. 128 89

It has been suggested that the kindling of seizures may depend on the induction of genes encoding enzymes involved in neurotransmission. Experimental seizures are followed by an especially rapid and massive induction of brain ornithine decarboxylase (ODC), an enzyme which catalyses the rate-limiting step in the synthesis of polyamines. The latter compounds have been shown to act as positive allosteric modulators of the NMDA receptor, and also to play an important role in cell growth and differentiation. The induction of ODC by seizures has accordingly been suggested to play a pivotal role in the changes in synaptic structure and function that underlie kindling. In the present study we examined the progress of kindling during treatment with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. We found that progressive increase in the duration and severity of kindled seizures and in the duration of local afterdischarges was unaffected by daily injections of DFMO in doses previously shown to cause substantial depression of brain ODC activity. Treatment with DFMO also failed to produce significant anticonvulsant or proconvulsant effects. Progressive increase in seizure activity during kindling is therefore unlikely to depend to any appreciable extent on enhanced synthesis of polyamines by ODC.
 ...
PMID:Ornithine decarboxylase induction and polyamine synthesis in the kindling of seizures: the effect of alpha-difluoromethylornithine. 156 37

Ornithine decarboxylase (ODC; EC 4.1.1.17) is a highly inducible, rate-limiting enzyme of the polyamine pathway. We have studied the mechanisms that lead to the induction of ODC activity in response to electrical stimulation in three brain regions. Hippocampal ODC activity was found to exhibit much larger elevations than that of the neocortex and the cerebellum. The levels of ODC gene expression were also followed to examine its relationship to the existing regional differences in ODC activity. In the neocortex, there was an elevation of both the ODC mRNA and enzyme activity. However, the hippocampal ODC mRNA level was not increased by electroconvulsive shock. Furthermore, the effects of hormonal changes and seizures on these regional differences in ODC induction were also examined. Adrenalectomy did not affect ODC activity, but pretreatment with the anticonvulsant MK-801 caused a depression of the induced levels of enzyme activity. Our data suggest that ODC activity in all the brain regions studied is directly elevated by electrically stimulated seizures. However, this induced ODC activity may or may not involve enhanced gene expression.
 ...
PMID:Transcription-dependent and -independent induction of cerebral ornithine decarboxylase. 172 14

The induction of the activity of cerebral ornithine decarboxylase (EC 4.1.1.17) and mRNA by electrical stimulation exhibits regional differences. The effects of the enzyme inhibitor difluoromethylornithine on these regional variations was examined. Administration of this inhibitor resulted in pronounced depression of both basal and induced activity of ornithine decarboxylase in the hippocampus. Basal activity of the enzyme in the neocortex and the cerebellum appeared to be resistant to difluoromethylornithine but the induced enzyme activity was sensitive to the effects of this inhibitor. Susceptibility to difluoromethylornithine may be directly correlated with a slower turnover rate for ornithine decarboxylase. These results suggest that ornithine decarboxylase in the hippocampus may possess a longer half-life than its counterparts in other regions of the brain. Pretreatment with difluoromethylornithine had no effect on the induced ornithine decarboxylase mRNA in the neocortex. Thus, elevated activity of ornithine decarboxylase enzyme, due to electrical stimulation, appears to not have any effect on either the transcription or the decay rate of the induced ornithine decarboxylase mRNA. These findings support the concept of region-specific regulation of cerebral ornithine decarboxylase.
 ...
PMID:Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA. 185 67

Fetal lung beta-receptors become effectively coupled to lung fluid reabsorption and enzymes involved in surfactant synthesis on the day before birth, a period when circulating catecholamine levels are high. Accordingly, we examined the effects of repeated maternal terbutaline exposure on beta-receptor binding capabilities and beta-receptor-mediated processes in the fetal rat lung. Administration of terbutaline to pregnant rats on gestational day 17-20 produced significant reductions in beta-receptor binding to membrane preparations. Similarly, beta-receptor-mediated stimulation of adenylate cyclase activity and ornithine decarboxylase activity showed marked desensitization in the terbutaline-exposed fetuses. However, the linkage of beta-receptors to lung fluid reabsorption and phosphatidic acid phosphatase, an enzyme involved in surfactant synthesis, did not desensitize with chronic terbutaline pretreatment; both of these processes displayed the normal onset of responsiveness on gestational day 21 in the treated animals, as well as a normal magnitude of response. Hence, beta-receptor-mediated events in the developing lung may be differentially regulated during exposure to agonists, allowing the selective expression or depression of function when circulating catecholamine levels are high.
 ...
PMID:Regulation of beta-adrenergic receptor-mediated processes in fetal rat lung: selective desensitization caused by chronic terbutaline exposure. 196 39


1 2 3 4 Next >>