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

---

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

The cytotoxic effect of aluminium was studied on cultured goat brain microvascular endothelial cells used as an in vitro model of the blood-brain barrier. Confluent monolayers of these cells were exposed for 4 days to aluminium maltol and, for control purposes, to maltol alone, and also to cadmium chloride as a known cytotoxic substance. The localization of plasmalemma-bound enzymatic activities of 5'-nucleotidase and Ca(2+)-ATPase and the distribution of sialic acid residues were studied at the ultrastructural level. It was observed that the reaction for 5'-nucleotidase activity was only insignificantly affected, indicating its resistance to the cytotoxic action of both substances used. On the contrary, the activity of Ca(2+)-ATPase was evidently suppressed, especially in the interendothelial clefts where junctional complexes are presumably to be formed. Aluminium also affects the density of sialic acid residues, as shown by their redistribution, leading to the appearance of relatively long segments of unlabelled apical cell surface. The data obtained suggest that observed changes in the localization of Ca(2+)-ATPase and sialic acid residues can lead ultimately to impairment of the formation and maintenance of intercellular junctions and to disturbances in the negatively charged domains of the endothelial cell surface. Whether these alterations, induced in vitro, contribute to in vivo disturbances of blood-brain barrier function requires further experimental study.
...
PMID:Cytochemical study of the effect of aluminium on cultured brain microvascular endothelial cells. 815 Jun 59

Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg(2+)-ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 45Ca-uptake in microsomes and Ca(2+)-ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long-Evans rats. ATP-dependent 45Ca-uptake was similar in microsomes from both brain regions. The addition of 50-800 microM AlCl3 resulted in a concentration-dependent inhibition of 45Ca-uptake. Mg(2+)-dependent Ca(2+)-ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, AlCl3 stimulated Mg(2+)-dependent Ca(2+)-ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg2+ or AlCl3. Maximal ATPase activity was obtained between 3 and 6 mM Mg2+. When we substituted AlCl3 for Mg2+, ATPase activity was also stimulated in a concentration-dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg2+ and Ca2+, increasing the activity of the Ca(2+)-ATPase, but disrupting transport of calcium.
...
PMID:Aluminum alters calcium transport in plasma membrane and endoplasmic reticulum from rat brain. 815 28

Comparison of the effects of fluoride (NaF, 1-10 mM) on the catalytic and ion transport functions of the Ca(2+)-ATPase in sarcoplasmic reticulum (SR) vesicles isolated from rabbit cardiac and fast-twitch skeletal muscles revealed similarities as well as striking tissue-specific differences depending on the experimental conditions employed. Short preincubation (3 min at 37 degrees C) of cardiac or fast muscle SR with fluoride in the absence of Ca2+ and ATP prior to initiating enzyme turnover by simultaneous addition of Ca2+ and ATP to the assay medium resulted in a strong inhibitory effect of fluoride on ATP-energized (oxalate-facilitated) Ca2+ uptake and Ca(2+)-ATPase activity. On the other hand, when turnover was initiated by the addition of ATP to SR preincubated with fluoride in the presence of Ca2+ but in the absence of ATP, fluoride caused concentration-dependent stimulation of active Ca2+ uptake by fast muscle SR with no appreciable change in Ca(2+)-dependent phosphoenzyme (EP) formation (from ATP) or Ca(2+)-ATPase activity but inhibition of active Ca2+ uptake by cardiac SR with concomitant inhibition of EP formation and Ca(2+)-ATPase activity. Exposure of cardiac or fast muscle SR to fluoride in the presence of both Ca2+ and ATP resulted in concentration-dependent stimulatory effect of fluoride on Ca2+ uptake with no change in EP formation or Ca(2+)-ATPase activity, this effect diminished substantially at saturating oxalate concentration in the assay. Assessment of the effects of deferoxamine (1 mM) and exogenous aluminum (10 microM) did not indicate a requirement for aluminum in the inhibitory or stimulatory effect of fluoride. These results suggest that (a) the Ca2+ and ATP-deprived (E1/E2) but not the Ca2+ plus ATP-liganded (CaE1ATP) conformation of the SR Ca(2+)-ATPase is susceptible to inhibition by fluoride in both cardiac and fast muscle; (b) the Ca(2+)-bound conformation (CaE1) of the SR Ca(2+)-ATPase is susceptible to inhibition in cardiac muscle but is refractory to fluoride in fast muscle; and (c) the stimulatory effect of fluoride is largely secondary to its ability to mimic the action of oxalate in intravesicular Ca2+ trapping when the fluoride-resistant enzyme is turning over normally. Fluoride inhibited phosphorylation of the Ca(2+)-free enzyme by Pi in cardiac and fast muscle SR indicating that fluoride sensitivity of the phosphorylation site of the SR Ca(2+)-ATPase is similar in cardiac and fast muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Comparison of the effects of fluoride on the calcium pumps of cardiac and fast skeletal muscle sarcoplasmic reticulum: evidence for tissue-specific qualitative difference in calcium-induced pump conformation. 817 9

This investigation examined the relationship between alteration of Ca(2+)-transport systems and cytotoxicity in vitro for a number of neuroactive chemicals including environmental pollutants. 45Ca2+ uptake as a measure of Ca2+ sequestration was determined in mitochondria and microsomes isolated from cerebella of adult male Long-Evans hooded rats by differential centrifugation. Ca2+ extrusion, measured as Ca(2+)-ATPase activity, was determined in synaptosomes prepared by sucrose density gradient. Cytotoxicity (lactate dehydrogenase leakage) was assessed in primary cultures of cerebellar granule cells from 6- to 8-day-old Long-Evans rats. N-Methyl-D-aspartic acid (NMDA) did not alter synaptosomal Ca(2+)-ATPase activity or 45Ca2+ uptake in mitochondria and microsomes. However, chlorpromazine (CPZ), aluminum (Al), permethrin (PER), and deltamethrin (DEL) inhibited Ca2+ sequestration by mitochondria and microsomes. The IC50 values (microM) for CPZ, Al, PER, and DEL were 67.8, 671, 4.2, and 91.2 for mitochondrial 45Ca2+ uptake, and 129.9, 1384, > 50, and > 200 for microsomal 45Ca2+ uptake, respectively. CPZ, PER, and DEL also inhibited synaptosomal Ca(2+)-ATPase activity in a concentration-dependent manner with IC50 values of 62.5, > 400, and 246.9 microM, indicating an effect on the Ca(2+)-extrusion process. Al increased Ca(2+)-ATPase activity (EC50 = 833 microM). Although NMDA did not inhibit Ca(2+)-transport systems, it was cytotoxic at 250 microM and higher concentrations after 2 hr of exposure. Similarly, CPZ was cytotoxic at concentrations of 25 and 10 microM after 4 hr exposure. However, PER, DEL, and Al were not cytotoxic at any concentration up to 500 microM. Of all the chemicals tested, CPZ was the most potent in inhibiting Ca(2+)-transporting systems and was also cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of selected neuroactive chemicals on calcium transporting systems in rat cerebellum and on survival of cerebellar granule cells. 825 84

Polyclonal BALB/C mouse and New Zealand White rabbit anti-idiotypic antibodies were raised by immunization with a protein G-purified burro anti-saxitoxin IgG antibody preparation. Following absorption of non-anti-idiotype reactivity, murine and rabbit IgG were purified by protein A chromatography and used to immunize BALB/C mice for the induction of anti-saxitoxin antibody responses. Unconjugated BALB/C anti-idiotypes did not induce significant anti-saxitoxin reactivity in BALB/C mice, even after repeated immunizations. However, BALB/C mice immunized with purified BALB/C anti-idiotypes conjugated to keyhole limpet hemocyanin, or with purified, unconjugated rabbit anti-idiotypes, as aluminum hydroxide precipitates, induced significant and specific anti-saxitoxin immune responses. Saxitoxin, a sodium channel blocker, can protect cells treated with veratridine and ouabain, whose respective actions are to open sodium channels and to block the activity of Na/K-ATPase. The anti-idiotype-induced anti-saxitoxin antibodies inhibited saxitoxin from protecting against cell death induced by veratridine and ouabain treatment. These and other published experimental results strengthen the concept of anti-idiotype-based vaccines in eliciting protective immunity against a variety of low molecular weight, nonproteinaceous biological and chemical toxins, whose extreme toxicity does not allow their use as safe immunogens.
...
PMID:Polyclonal anti-idiotypes induce specific anti-saxitoxin antibody responses. 828 43

We studied the effect of chronic exposure (6 weeks and 6 months) of mice to drinking (tap) water containing 1.76% (0.06 M) aluminum lactate on some cytochemical properties of the blood-brain barrier (BBB). The plasmalemma-bound enzymatic activities of alkaline phosphatase (AP) and Ca(2+)-activated adenosine triphosphatase (Ca(2+)-ATPase) were studied at the ultrastructural level. Anionic sites were localized with cationized ferritin in a pre-embedding procedure and with cationic colloidal gold in a post-embedding procedure applied to brain samples embedded in Lowicryl K4M. Intravenously injected Evans blue and horseradish peroxidase (HRP) were used for evaluation of the functional state of the BBB. The results indicate that chronic exposure to aluminum does not noticeably affect barrier function of the endothelium of cerebral cortex blood microvessels. Focal leakage of larger than capillary microvessels (presumably arterioles and venules) was observed only in a few areas, such as the basal ganglia and amygdaloid nuclei. The localization of both enzymatic activities (AP and Ca(2+)-ATPase) in microvessels remained essentially unchanged. The localization of anionic sites was also unchanged except on the luminal surface of the endothelium of a few blood microvessels located in areas of the brain where leakage of the injected HRP was noted. In these vessels the injected HRP was often attached to the luminal surface of the endothelial cells, suggesting its increased stickiness. These data, compared with our previous observations on brain microvascular endothelial cells growing in vitro, indicate that cytotoxicity of aluminum is evidently less pronounced in the living organism, presumably due to action of detoxicating and regulatory mechanisms.
...
PMID:Ultracytochemical studies of the effects of aluminum on the blood-brain barrier of mice. 828 66

Effect of aluminum (Al) has been investigated on the brain of rats exposed to this metal (500 mg Al/liter in drinking water) daily for 180 days. A significant reduction in the spontaneous locomotor activity was noticed after 90 and 180 days of Al exposure to the rats, the magnitude of the change being almost identical at both the time intervals. Aluminum exposure also produced significant deficits in acquisition and retention of learned response in active avoidance situation, these changes being time dependent. A significant retardation of the extinction of the learned task was noted in Al exposed rats especially at 180 days. There was significant increase in the lipid peroxidation and decrease in the activity of Mg(2+)-ATPase and Na+,K(+)-ATPase in the brain of rats at 180 days after Al exposure. The increase in the contents of the metal was maximum in rest of the brain region (87% of control) followed by hippocampus and cerebral cortex (59% of controls), cerebellum and corpus striatum (43% and 44% of controls, respectively) after 180 days. Whether Al is responsible to initiate neurotoxic effects by producing changes in the structure and function of the plasma membrane needs further investigations.
...
PMID:Aluminum ingestion alters behaviour and some neurochemicals in rats. 850 Aug 14

Aluminum (Al(III)) is a well established toxicant implicated as an etiological factor in several neuropathies. In this paper we report results regarding opposite effects produced by Al(III) on the activity of two enzymes utilized as models. While sodium-potassium ATP-ase (Na/K-ATPase) is strongly activated by Al(III) in a dose-effect dependent way, on the contrary, carbonic anhydrase (CA) is remarkably inhibited. The relevance of the metal speciation together with the enzymatic structural modification demonstrated by circular dichroism measurements could explain the observed modified enzymatic activities. In addition, a new experimental protocol for the preparation of Al(III) solutions at physiological pH useful in the standardization of Al(III) experimental toxicology is also proposed and discussed.
...
PMID:Different effects of aluminum upon carbonic anhydrases and Na+/K+-ATPase activities in rat. 854 58

Actin exhibits ATPase activity of unknown function that increases when monomers polymerize into filaments. Differences in the kinetics of ATP hydrolysis and the release of the hydrolysis products ADP and inorganic phosphate suggest that phosphate-rich domains exist in newly polymerized filaments. We examined whether the enrichment of phosphate on filamentous ADP-actin might modulate the severing activity of gelsolin, a protein previously shown to bind differently to ATP and ADP actin monomers. Binding of phosphate, or the phosphate analogs aluminum fluoride and beryllium fluoride, to actin filaments reduces their susceptibility to severing by gelsolin. The concentration and pH dependence of inhibition suggest that HPO4(2-) binding to actin filaments generates this resistant state. We also provide evidence for two different binding sites for beryllium fluoride on actin. Actin has been postulated to contain two Pi binding sites. Our data suggest that they are sequentially occupied following ATP hydrolysis by HPO4(2-) which is subsequently titrated to H2PO4-. We speculate that beryllium fluoride and aluminum fluoride bind to the HPO4(2-) binding site. The cellular consequences of this model of phosphate release are discussed.
...
PMID:Binding of phosphate, aluminum fluoride, or beryllium fluoride to F-actin inhibits severing by gelsolin. 861 30

We have examined the energetics of the interactions of two kinesin constructs with nucleotide and microtubules to develop a structural model of kinesin-dependent motility. Dimerization of the constructs was found to reduce the maximum rate of the microtubule-activated kinesin ATPase 5-fold. Beryllium fluoride and aluminum fluoride also reduce this rate, and they increase the affinity of kinesin for microtubules. By contrast, inorganic phosphate reduces the affinity of a dimeric kinesin construct for microtubules. These findings are consistent with a model in which the kinesin head can assume one of two conformations, "strong" or "weak" binding, determined by the nature of the nucleotide that occupies the active site. Data for dimeric kinesin are consistent with a model in which kinesin.ATP binds to the microtubule in a strong state with positive cooperativity; hydrolysis of ATP to ADP+P(i) leads to dissociation of one of the attached heads and converts the second, attached head to a weak state; and dissociation of phosphate allows the second head to reattach. These results also argue that a large free energy change is associated with formation of kinesin.ADP.P(i) and that this step is the major pathway for dissociation of kinesin from the microtubule.
...
PMID:Equilibrium studies of kinesin-nucleotide intermediates. 862 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---