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)

Hereditary spongiform dystrophy in young children is characterised by macrocephaly with spasticity, convulsions and ultimately a decerebrate state and diffuse electroencephalographic changes. Histological examination of the brain remains essential for its diagnosis. A review of the ultrastructural studies reported by various authors complements the findings obtained by conventional histology. We have thus endeavoured to determine whether van Bogaert-Bertrand's disease is to be considered as congenital or acquired. The anatomical findings in 3 cases together with the descriptions of other authors lead us to the following conclusions: -that the spongiform changes may be due to an osmolar disequilibrium in which the ATPase-Na/K relation with mitochondrial abnormalities is yet unclear. -that the constant finding of Alzheimer type II cells is certainly an indication of intra-astrocytic malfunction. -that the oedema blocks both myelin synthesis and its coiling into lamellae. Case 1, which showed a long survival compared to others described (about 4 years), enabled us to study terminal lesions. Sub-cortical zones, in both cerebrum and cerebellum, contained neither myelin nor spongiform cavities, but, on the other hand, showed a compact glio-fibrillosis with large vesicles and oligodendroglia of increased density. We have interpreted these lesions, progressively replaced by spongiosis deeper in the cortex, as evidence of retracted scar tissue. Differences found between cerebral weights seem to confirm this hypothesis.
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PMID:[Hereditary spongiform dystrophy in young children (Canavan: van Bogaert-Bertrand)]. 127 Oct 80

Piracetam, ig 600 mg.kg-1.d-1 for 30 d, caused a 20% decrease in the activity of Na(+)-K(+)-ATPase and monoamine oxidase (MAO) in vivo. In vitro, it presented an inhibitory effect on MAO, but had no direct effect on Na(+)-K(+)-ATPase at a concentration of 100 mmol.L-1. Piracetam had a potential action in scavenging free radicals. This action may be related to its clinical effects on amnesia and Alzheimer's disease.
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PMID:[Effects of piracetam on Na(+)-K(+)-ATPase and monoamine oxidase in rat brain and its antioxidation effect]. 131 32

These studies were performed to determine the changes that occur in Na+/Ca2+ exchange activity in Alzheimer's disease (AD) brain tissues. Cerebral plasma membrane vesicles were purified by sucrose density gradient centrifugation from frozen postmortem hippocampal/temporal cortex tissue slices derived from age matched brains of normal, AD and non-Alzheimer dementia (NAD) origin (autopsy confirmed). Membrane marker assays (Na/K ATPase, muscarinic receptor, cytochrome c oxidase) revealed no change in membrane purity across different preparations. Thin-section electron microscopy revealed predominantly intact unilamellar vesicles. Vesicles were preincubated for 15 min (37 degrees C) in buffer containing 132 mM NaCl, 5 mM KCl, 1.3 mM MgCl2, 10 mM glucose and 10 mM HEPES (pH 7.4). Ca2+ uptake was initiated by diluting vesicles 20-fold with buffer containing either 132 mM NaCl or 132 mM choline chloride and 45CaCl2 then terminated by addition of 200 microM LaCl3 and rapid filtration. Ca2+ content increased rapidly at first and then maintained a steady plateau for up to 5 min. When the Ca2+ ionophore A23187 (10 microM) with 100 microM EGTA was added after 4 min, Ca2+ content was reduced to 10% of its original value. Ruthenium red (10 microM) had no effect on Ca2+ content. Na(+)-dependent Ca2+ uptake (Ca2+ content measured in choline chloride minus that measured in NaCl) was increased in AD brains as evidenced by both an increase in the initial rise in Ca2+ content and in elevated values of peak plateau Ca2+ content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na+/Ca2+ exchange activity is increased in Alzheimer's disease brain tissues. 164 56

Previous reports have suggested that the physical properties of cell membranes and calcium homeostasis in both the central and peripheral nervous system are changed in Alzheimer's disease (AD). This study has examined the biophysical properties of erythrocyte and platelet membranes by measuring the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and possible related changes in lipid peroxidation. In addition, we have studied calcium homeostasis by measuring thrombin-stimulated changes in intraplatelet free calcium and Ca2(+)-ATPase activity in AD and healthy age and sex-matched controls. Our results show that there was no significant difference in the fluorescence anisotropy of DPH in erythrocyte membranes isolated from the three groups. There was also no significant difference in lipid peroxidation levels in erythrocytes and plasma of AD patients compared to controls. However, there was a significant reduction in the fluorescence anisotropy of DPH in platelet membranes from AD patients, compared with healthy controls. Recent evident suggests that the increase in platelet membrane fluidity results from alterations in internal membranes. We measured the specific activities of enzyme markers associated with intracellular and plasma membranes in platelets from AD patients and healthy controls. There was a significant reduction in the specific activity of antimycin A-insensitive NADH-cytochrome-c reductase (a specific marker for smooth endoplasmic reticulum (SER)), in AD patients compared to controls, but no change in the specific activity of bis(p-nitrophenyl)phosphate phosphodiesterase (a specific marker for plasma membrane). We have also shown that SER mediated [Ca2+] homeostasis is possibly impaired in AD platelets, i.e., the percentage of thrombin-stimulated increase in intraplatelet [Ca2+] above basal levels was significantly higher in AD compared to matched controls and there were significant reductions in the specific activities of Ca2+/Mg2(+)-ATPase and Ca2(+)-ATPase (but not Mg2(+)-ATPase) in AD platelets. Finally electron microscopic analysis of platelets showed that there was a significant increase in the incidence of abnormal membranes in AD patients compared to controls. The ultrastructural abnormalities seem to consist of proliferation of a system of trabeculated cisternae bounded by SER. These results suggest that both SER structure and function might be defected in AD platelets, which could explain the fluidity changes observed here.
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PMID:Platelet and erythrocyte membrane changes in Alzheimer's disease. 214

The Alz-50 immunoreactive proteins, designated A68, are detected by electrophoretic blot analysis of 100,000 x g pellet fractions of brain tissue from individuals with Alzheimer disease (AD). In exploring the biochemical nature of these proteins, we have found that a preincubation of such fractions with 5 mM ATP results in loss of Alz-50 immunoreactivity on immunoblots. The loss of antigenicity is complete after a 1-hr incubation at 37 degrees C and is stringently dependent on ATP. Hydrolysis of ATP is required, since the inhibition is not supported by the nonhydrolyzable analog adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]) and is prevented when the ATPase inhibitors o-vanadate and oligomycin are present. Upon further characterization, it was found that certain protease inhibitors, phenylmethylsulfonyl fluoride, antipain, tosylphenylalanine chloromethyl ketone, and aprotonin prevent the loss of the epitope. This suggests that hydrolysis of ATP is coupled with proteolysis of A68, leading to loss of Alz-50 immunoreactivity. Since a variety of proteins are believed to be degraded by an ATP/ubiquitin-dependent pathway, a possible role for ubiquitin (Ub) in this effect was investigated. Two polyclonal antibodies against Ub protected A68 from proteolysis and were also effective in immunoprecipitating A68 after incubation with ATP in the presence of Ub and phenylmethylsulfonyl fluoride. The proteolysis of A68 was also blocked by hemin, an inhibitor of the protease that cleaves Ub-protein conjugates. Taken together, these findings indicate that loss of Alz-50 immunoreactivity with A68 is due to ATP-dependent/Ub-mediated proteolysis. This mechanism may be relevant to the physiological role for A68 in AD or it may simply represent an attempt to abort an aberrant protein.
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PMID:ATP-induced loss of Alz-50 immunoreactivity with the A68 proteins from Alzheimer brain is mediated by ubiquitin. 216 59

Hexokinase, lactate dehydrogenase, acylphosphatase, (Na+,K+)-ATPase and Ca2(+)-ATPase of selected areas from postmortem Alzheimer's disease brains were studied. Hexokinase and lactate dehydrogenase were significantly changed in all the examined subcortical nuclei. (Na+,K+)-ATPase activity was altered in several areas of Alzheimer's disease brains. No changes in Ca2(+)-ATPase and acylphosphatase were observed. The main alterations of the assayed enzymes were observed in subcortical areas but not in cortical areas of Alzheimer's disease brains.
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PMID:Changes in Na+,K(+)-ATPase, Ca2(+)-ATPase and some soluble enzymes related to energy metabolism in brains of patients with Alzheimer's disease. 216 43

Differences between Alzheimer and control fibroblast [Ca2+ + Mg2+]-dependent ATPase activity at free Ca2+ concentration considerably higher than physiologic concentrations were observed. At 50 microM free Ca2+, Alzheimer and control fibroblast homogenates exhibited maximum velocity values ranging from 8 to 25 nmoles phosphate released/min/mg protein. Higher free Ca2+ (350 microM) inhibited control fibroblast ATPase activity approximately 77%; whereas, Alzheimer fibroblasts retained greater than 75% starting activity. Although the pathophysiological significance of these findings is at present unclear, these data suggest the Ca2+ pump of Alzheimer fibroblasts behaves differently in the presence of high free Ca2+. Such behavior may be of potential diagnostic value.
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PMID:Effects of free Ca2+ on the [Ca2+ + Mg2+]-dependent adenosinetriphosphatase (ATPase) of Alzheimer and normal fibroblasts. 253 59

We studied Na+,K+-adenosine triphosphatase by assaying specific tritiated ouabain binding in the frontal cortex, temporal cortex, hippocampus, putamen, cerebellum, and cerebral microvessels in subjects with Alzheimer's disease and control subjects. Ouabain binds specifically, in a saturable manner, and with a high affinity to a single class of binding sites in all the tissues studied. The density of ouabain binding sites was highest in cerebellum and frontal cortex (approximately 40 pmol/mg of protein); intermediate in temporal cortex, hippocampus, and putamen; and lowest in brain microvessels (approximately 8 pmol/mg of protein). The dissociation constant of binding was about 30 nmol/L in all tissues. In control subjects, there were no age-related alterations in ouabain binding, nor was there any correlation between ouabain binding and postmortem delay. However, there was a marked decrease in brain ouabain binding in subjects with Alzheimer's disease when compared with age-matched controls, especially in the cerebral cortex. Ouabain binding was also significantly decreased in the cerebellum and putamen of subjects with Alzheimer's disease even though these brain regions are not particularly affected in this disease. Ouabain binding to brain microvessels, which constitute the blood-brain barrier, was not significantly decreased in subjects with Alzheimer's disease. The decreased specific ouabain binding in the brain of subjects with Alzheimer's disease probably reflects the loss of neuronal membranes.
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PMID:Ouabain binding in the human brain. Effects of Alzheimer's disease and aging. 254 26

Kinetic properties of the [Ca2+ + Mg2+]-ATPase from one Alzheimer (AG0364B, 53-year-old donor) and one control fibroblast cell line (AG6009, 59-year-old donor) were examined. A saturation plot revealed the control fibroblast ATPase activity to saturate at approximately 500 nM free Ca2+; whereas, the Alzheimer activity saturated at approximately 1000 nM. Eadie Hofstee graphical analysis indicated almost identical Vmax values, 19.5 and 21.0 nmoles phosphate released/min/mg protein for the Alzheimer and control fibroblasts, respectively. However, an approximately two-fold higher Km value of 350 nM was observed for the Alzheimer fibroblast homogenate in contrast to 220 nM for the control. In a previous study, a kinetic difference in Alzheimer fibroblast [Ca2+ + Mg2+]-ATPase activity at high free Ca2+ concentration was observed. The difference in affinity reported in this study at low free Ca2+ concentrations supports further the hypothesis that abnormalities in Ca2+ homeostasis might be involved in the etiology of Alzheimer's disease.
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PMID:Kinetic properties of the [Ca2+ + Mg2+]-ATPase in Alzheimer and normal fibroblasts at low free calcium. 297 26

Electron spin resonance, enzymatic, and SDS-polyacrylamide gel electrophoretic investigations of erythrocyte membranes from patients with Alzheimer's disease were performed. Alterations in the physical state of membrane proteins in Alzheimer's disease erythrocytes were found by spin labeling studies. However, no alterations in membrane lipid fluidity or in the activities of membrane-bound sodium plus potassium-stimulated, magnesium-dependent adenosine triphosphatase or acetylcholinesterase could be demonstrated. Also, no changes in staining profiles of AD erythrocyte membrane proteins subjected to electrophoresis were observed. The altered conformation and/or organization of extraneural membrane proteins in Alzheimer's disease suggests the possibility that this disorder may have more widespread membrane involvement than was originally thought.
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PMID:Spin label and biochemical studies of erythrocyte membranes in Alzheimer's disease. 624 87


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