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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of short- and long-chain fatty acids on the cerebromicrovascular (Na+ + K+)-ATPase were investigated using specific [3H]ouabain binding to the enzyme. Specific binding increased linearly with total microvessel protein (37-110 micrograms) and was time-dependent with maximum binding obtained by 10 min. Arachidonic acid, but not palmitic acid, stimulated [3H]ouabain binding in a dose-dependent manner, with a 105% increase over basal levels at 100 microM arachidonic acid. Preincubation of the microvessels with arachidonic acid did not alter the stimulation observed. 4-Pentenoic acid stimulated [3H]ouabain binding only at high concentrations (10 mM). Scatchard analysis of [3H]ouabain binding to untreated microvessels yielded a single class of "high-affinity" binding sites with an apparent binding affinity (KD) of 64.7 +/- 2.0 nM and a binding capacity (Bmax) of 10.1 +/- 1.5 pmol/mg protein. In the presence of 100 microM arachidonic acid, a monophasic Scatchard plot also was obtained, but the KD significantly decreased to 51.9 +/- 2.7 nM (p less than 0.01), whereas the Bmax remained virtually unchanged (12.5 +/- 1.2 pmol/mg protein). The stimulation of [3H]ouabain binding in the presence of arachidonic acid was potentiated by 4-pentenoic acid, but not by indomethacin or eicosatetraynoic acid. These data suggest that long-chain polyunsaturated fatty acids may be involved in the regulation of blood-brain barrier (Na+ + K+)-ATPase and may play a role in the cerebral dysfunction associated with diseases in which plasma levels of nonesterified fatty acids are elevated.
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PMID:Effect of fatty acids on [3H]ouabain binding to cerebromicrovascular (Na+ + K+)-ATPase. 283

In order to elucidate molecular mechanisms underlying brain dysfunction in offspring exposed to ethanol in utero, subclinical doses of ethanol that do not have apparent structural effect on the offspring were administered intraperitoneally to pregnant rats at various gestational stages. We measured the activity of membrane marker enzymes and the level of mRNA of myelin proteins of the offspring brain. The activity of a myelin specific enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased in ethanol-exposed offspring. This effect was not related to the period of gestation or the dose of ethanol. Perikaryonal enzymes, acetylcholinesterase and Na+, K(+)-ATPase, were significantly affected in groups exposed to ethanol at early fetal stage and in high doses. Expression of mRNAs of CNP and myelin basic proteins decreased significantly in the ethanol-treated group, with abnormal developmental profile suggesting a relationship with delayed myelination in offspring exposed to ethanol in utero. The present findings suggest that in spite of the low doses of ethanol that do not cause clinical symptoms in the offspring, prenatal exposure to ethanol affects the level of mRNA of membrane enzyme proteins in the offspring brain, consequently causing a corresponding reduction in enzyme activity, that may lead to neuronal dysfunction. In a separate study, blood ethanol levels were found to reach a maximum level within 30 min after injection and be undetectable after 5 to 10 h. No accumulation effects due to daily injection were observed.
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PMID:Prenatal ethanol exposure affects the activity and mRNA expression of neuronal membrane enzymes in rat offspring. 752 23

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine (Arg) and other guanidino compounds (GC). Convulsions, lethargy and psychomotor delay are predominant clinical features of this disease. Considering that some GC are epileptogenic and cause a decrease in membrane fluidity and that Na+,K(+)-ATPase, a membrane-bound enzyme, is essential for cellular excitability and is decreased in experimental and human epilepsy, in the present study we determined the in vitro effects of Arg, N-acetylarginine (NAA), argininic acid (AA) and homoarginine (HA) on the activity of Na+,K(+)-ATPase in the synaptic plasma membrane from cerebral cortex of young rats in the hope to identify a possible mechanism for the brain damage in hyperargininemia. The results showed that all GC tested, except Arg, significantly inhibited Na+,K(+)-ATPase activity at concentrations similar to those observed in plasma and CSF of patients with hyperargininemia. In addition, competition between NAA, AA and HA for the binding to the enzyme was observed, suggesting a common binding site for the GC. It is therefore possible that the inhibitory effect of GC on Na+,K(+)-ATPase may be related to the brain dysfunction observed in hyperargininemia.
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PMID:In vitro inhibition of Na+,K(+)-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperargininemia. 1044 19

Na+, K+-ATPase activity was measured in synaptic plasma membrane from cerebral cortex of Wistar rats subjected to experimental phenylketonuria, i.e., chemical hyperphenylalaninemia induced by subcutaneous administration of 5.2 micromol phenylalanine / g body weight (twice a day) plus 0.9 micromol p-chlorophenylalanine / g body weight (once a day). The treatment was performed from the 6th to the 14th postpartum day and rats were killed 12 h after the last injection. Synaptic plasma membrane from cerebral cortex was prepared by a discontinuous density sucrose gradient for Na+, K+-ATPase activity determination. The results showed that the enzyme activity was decreased by 30% in animals subjected to experimental phenylketonuria when compared to control. The in vitro effects of the drugs on Na+, K+-ATPase activity were also investigated. Phenylalanine and p-chlorophenylalanine inhibited the enzyme activity and this inhibition was reversed by alanine. In addition, competition between phenylalanine and p-chlorophenylalanine for binding to the enzyme was observed, suggesting a common binding site for these substances. Our results suggest that reduction of Na+, K+-ATPase activity may be one of the mechanisms related to the brain dysfunction observed in human PKU.
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PMID:Effect of phenylalanine and p-chlorophenylalanine on Na+, K+-ATPase activity in the synaptic plasma membrane from the cerebral cortex of rats. 1109 77

Homocystinuria is an inborn error of sulfur amino acid metabolism characterized predominantly by vascular and nervous system dysfunction. In this study we determined the in vitro effects of homocysteine and methionine, metabolites which accumulate in homocystinuria, on Na+, K+-ATPase, and Mg2+-ATPase activities in synaptic membranes from the hippocampus of rats. The results showed that both metabolites significantly inhibit Na+, K+-ATPase but not Mg2+-ATPase activity at concentrations usually observed in plasma of homocystinuric patients. Furthermore, incubation of hippocampal homogenates with homocysteine also elicited an inhibition of the enzyme activity which was however prevented by the simultaneous addition of cysteine to the medium. In addition, cysteine or methionine per se did not modify the two enzymatic activities. These findings indicate that oxidation of critical groups in the enzyme may possibly be involved in homocysteine inhibitory effect. Moreover, kinetic studies performed to investigate the interaction between homocysteine and methionine on Na+, K+-ATPase inhibition suggested a common site for the two amino acids in the enzyme. Considering the critical role exerted by Na+, K+-ATPase in brain, it is proposed that the inhibition provoked by homocysteine and methionine on the enzyme activity may be possibly related to the brain dysfunction characteristic of homocystinuria.
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PMID:Inhibition of Na+, K+-ATPase activity by the metabolites accumulating in homocystinuria. 1208 40

We evaluated the effects of 7-nitroindazole, a selective neuronal nitric oxide synthetase (nNOS) inhibitor, on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglets. The decreased cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products, indicative of bilirubin-induced brain damage, were significantly attenuated by 7-nitroindazole treatment. 7-Nitroindazole also significantly improved the bilirubin-induced reduction in both brain ATP and phosphocreatine levels, decreased blood-to-brain glucose ratio and increased brain lactate level. In summary, 7-nitroindazole significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest that nitric oxide produced by nNOS is involved in mediating or facilitating bilirubin-induced cerebral dysfunction.
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PMID:Effect of 7-nitroindazole on bilirubin-induced changes in brain cell membrane function and energy metabolism in newborn piglets. 1211 43

Hyperhomocysteinemia occurs in homocystinuria, an inherited metabolic disease clinically characterized by thromboembolic episodes and a variable degree of neurological dysfunction whose pathophysiology is poorly known. In this study, we induced elevated levels of homocysteine (Hcy) in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by injecting subcutaneously homocysteine (0.3-0.6 micromol/g of body weight) twice a day at 8-hr intervals from the 6th to the 28th postpartum day. Controls received saline in the same volumes. Na(+),K(+)-ATPase and Mg(2+)-ATPase activities were determined in the hippocampus of treated Hcy- and saline-treated rats. Chronic administration of Hcy significantly decreased (40%) Na(+),K(+)-ATPase activity but did not alter Mg(2+)-ATPase activity. Considering that Na(+),K(+)-ATPase plays a crucial role in the central nervous system, our results suggest that the brain dysfunction found in homocystinuria may be related to the reduction of brain Na(+),K(+)-ATPase activity.
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PMID:Reduction of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. 1251 10

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity without affecting Mg2+-ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH, trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L-NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT-deficient patients.
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PMID:Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. 1524 54

Since a previous study demonstrated that ovariectomized rats present an activation of Na(+), K(+)-ATPase and acetylcholinesterase (AChE) activities, in the present study we investigated the influence of vitamins E plus C or soy isoflavones on the effects elicited by ovariectomy on the activities of these enzyme in hippocampus of ovariectomized rats. We also determined the effect of the same compounds on the reduction of serum butyrylcholinesterase (BuChE) activity caused by ovariectomy. Female adult Wistar rats were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries) and ovariectomized. Seven days after surgery, animals were treated for 30 days with a single daily intraperitoneous injection of vitamins E (40 mg/kg) plus C (100 mg/kg) or saline (control). In another set of experiments, the rats were fed for 30 days on a special diet with soy protein or a standard diet with casein (control). Rats were sacrificed after treatments and the hippocampus was dissected and serum was separated. Data demonstrate that vitamins E plus C reversed the activation of Na(+), K(+)-ATPase and AChE in hippocampus of ovariectomized rats. Conversely, soy protein supplementation reversed the increase of AChE activity, but not of Na(+), K(+)-ATPase activity, caused by ovariectomized group. Neither treatment was able to reverse the reduction of serum BuChE activity. Furthermore, treatments with vitamins E plus C or soy were unable to reverse the decrease in estradiol levels caused by ovariectomy. Our findings show that the treatment with vitamins E plus C significantly reversed the effect of ovariectomy on hippocampal Na(+), K(+)-ATPase and AChE activities. However, a soy diet that was rich in isoflavones was able to reverse just the increase of AChE. Neither treatment altered the reduction in serum BuChE activity. Taken together, these vitamins and soy may have a protective role against the possible brain dysfunction observed in some menopause women. Vitamins E plus C and soy isoflavones may be a good alternative as a novel therapeutic strategy.
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PMID:Supplementation with vitamins E plus C or soy isoflavones in ovariectomized rats: effect on the activities of Na(+), K (+)-ATPase and cholinesterases. 1751 15

In the present study we first investigated the in vitro and in vivo effects of proline on glutamate uptake in the cerebral cortex and hippocampus slices of rats. The action of alpha-tocopherol and/or ascorbic acid on the effects elicited by administration of proline was also evaluated. For in vitro studies, proline (30.0 microM and 1.0 mM) was added to the incubation medium. For acute administration, 29-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or saline (control) and were sacrificed 1 h later. Results showed that addition of proline in the assay (in vitro studies) reduces glutamate uptake in both cerebral structures. Administration of proline (in vivo studies) reduces glutamate uptake in the cerebral cortex, but not in the hippocampal slices of rats. In another set of experiments, 22-day-old rats were pretreated for one week with daily administration of alpha-tocopherol (40 mg/kg) or ascorbic acid (100 mg/kg) or with both vitamins. Twelve hours after the last vitamins injection, rats received a single injection of proline or saline and were killed 1 h later. Pretreatment with alpha-tocopherol and/or ascorbic acid did not prevent the effect of proline administration on glutamate uptake. alpha-Tocopherol plus ascorbic acid prevented the inhibitory effect of acute hyperprolinemia on Na(+),K(+) -ATPase activity in the cerebral cortex of 29-day-old rats. The data indicate that the effect of proline on reduction of glutamate uptake and Na(+),K(+) -ATPase activity may be, at least in part, involved in the brain dysfunction observed in hyperprolinemic patients.
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PMID:Proline promotes decrease in glutamate uptake in slices of cerebral cortex and hippocampus of rats. 1802 1


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