Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat brain (Na+ + K+)-adenosine triphosphatase is inhibited by ethanol (EtOH) in vitro, the inhibition being greater in the presence of norepinephrine (NE). Enzyme preparations from EtOH-tolerant rats show less inhibition by EtOH in vitro and less sensitization by NE. To investigate the mechanism of these changes, the enzyme activity of brain microsomes from tolerant and sucrose-control rats was measured at temperatures from 10-40 degrees C. Preparations from nonwithdrawn and 24-hr withdrawn rats were studied in the absence of in vitro additions, and in the presence of 1 microM NE, 50 mM EtOH or 440 mM EtOH separately, and of 1 microM NE + 50 mM EtOH. From Arrhenius plots of the results, the transition temperature (Td) was calculated by a method of successive approximations, and the activation energies were calculated from the segments above and below Td. Chronic EtOH treatment significantly decreased Td, but increased activation energies below Td. These findings suggest different effects on membrane matrix lipids than on boundary lipids adjacent to the enzyme. However, EtOH-tolerant preparations showed less effect of EtOH in vitro than did control preparations, on both Td and activation energies. Preparations from EtOH-tolerant and withdrawn rats behaved almost identically, indicating that the changes accompany tolerance and are not withdrawal effects. NE + 50 mM EtOH produced the same effects as 440 mM EtOH alone, in all preparations. EtOH tolerance reduced the sensitizing effect of NE. EtOH is interpreted as affecting both the boundary lipids and the apoenzyme itself.
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PMID:Effect of chronic ethanol treatment on temperature dependence and on norepinephrine sensitization of rat brain (Na+ + K+)-adenosine triphosphatase. 629 Jun 43

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/QO2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents. Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.
Recent Dev Alcohol 1984
PMID:Hypermetabolic state and hypoxic liver damage. 632 88

The effects of chronic alcohol consumption on nitrosamine metabolism in vivo, DNA synthesis and repair, and carcinogen-induced preneoplasia were studied in rat liver. Following a single injection of different doses of 14C-N-nitrosodimethylamine, there was no significant difference between controls and ethanol-pretreated rats in the alkylation pattern of cellular protein nor in the levels of the alkylation products 7-methylguanine and O6-methylguanine isolated from liver DNA. O6-Methylguanine-specific DNA repair was also unchanged. An increase in the number and size of foci staining negative for adenosine triphosphatase and/or positive for gamma-glutamyltranspeptidase was observed in rats treated intermittently with ethanol and N-nitrosomorpholine. The numbers of clear-cell and mixed-cell foci were also increased. An ethanol-mediated enhancement of DNA synthesis, which was ascertained by different methods, may be related to this cocarcinogenic action of the alcohol. Ethanol, however, failed to demonstrate promoting activity. Long-term treatment of carcinogen pretreated rats with ethanol, according to the classical initiation-promotion protocol, had no effect on the incidence of preneoplastic foci in liver.
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PMID:The mechanism of cocarcinogenic action of ethanol in rat liver. 653 12

In vivo ethanol exposure reduces in vitro Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) sensitivity to ethanol in some animal models, but very little is known about the effects of ethanol on human brain Na+,K(+)-ATPase. Cerebral cortex homogenates from 13 male alcoholic and 9 control subjects were assayed for K(+)-p-nitrophenylphosphatase (K(+)-pNPPase, a measure of Na+,K(+)-ATPase) and Mg(2+)-pNPPase activities at 37 degrees for 20 min in 75 mM imidazole-HCl (pH 7.4), 5 mM p-nitrophenylphosphate, 5 mM MgCl2, and 20 mM KCl, with or without 1 mM ouabain. Native K(+)-pNPPase activites were similar in control and alcoholic brains (61.5 +/- 3.5 vs 55.3 +/- 3.1 nmol/mg/min). In vitro exposure to a near lethal ethanol level (0.5%, or 110 mM) was without effect, whereas 5% ethanol inhibited K(+)-pNPPase activity by about 28% (P < 0.001) in both groups. Both 0.5 and 5% ethanol in vitro significantly stimulated Mg(2+)-pNPPase activity (1-2% and 19-20%, respectively). By comparison, mouse brain K(+)-pNPPase was inhibited significantly by in vitro ethanol, and Mg(2+)-pNPPase activity was unaffected. Ethanol levels attainable in humans may not be sufficient to alter significantly brain Na+,K(+)-ATPase activity.
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PMID:Effects of in vitro ethanol on the brain cation pump in alcoholics and controls. 805 41

The in vivo effect of the administration of extracts of Momordica charantia on certain biochemical parameters of Sprague-Dawley rats was investigated. It was observed that there was an increase in muscle and liver protein levels, while there was a reduction in the levels of brain protein, muscle and liver glycogen. The activities of plasma L-alanine transaminase and alkaline phosphatase were reduced. The L-aspartate transaminase and adenosine triphosphatase activities were slightly elevated in whole plant extract treated rats while the L-aspartate transaminase was unaffected by the ethanol extract but reduced the adenosine triphosphatase activity.
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PMID:Stimulation of protein biosynthesis in rat hepatocytes by extracts of Momordica charantia. 1126 4

Chronic ethanol exposure causes alterations in biologic membranes of different cell types. (Na + K) adenosine triphosphatase (ATPase), a membrane-bound enzyme inhibited by the acute presence of ethanol, increases its activity in rat kidney after chronic ethanol consumption. The aim of this investigation was to evaluate the effect of ethanol on the modulation of (Na + K)-ATPase by glucocorticoids and mineralocorticoids in renal papillary collecting duct cells. Cultured renal papillary collecting duct cells were exposed to a medium containing 150 mM ethanol plus either 100 nM aldosterone or 10 nM dexamethasone. Control groups were cultured in the absence of ethanol and/or the hormones. Mg(2+)-ATPase was used as control enzyme. The activity of ATPases was measured by ATP hydrolysis. Ethanol increased the activities of (Na + K)-ATPase and Mg(2+)- ATPase in 29 and 33% of controls, respectively; only (Na + K)-ATPase activity was elevated in the presence of aldosterone or dexamethasone, whereas Mg(2+)-ATPase was unaltered by these hormones. The effects of aldosterone and dexamethasone on (Na + K)-ATPase activity were augmented by ethanol in 50 and 19% of controls, respectively. These results suggest that ethanol treatment enhances the upregulation of (Na + K)-ATPase activity by both aldosterone and dexamethasone, in cultured renal papillary collecting duct cells.
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PMID:Effect of ethanol on regulation of (Na + K)-adenosine triphosphatase by aldosterone and dexamethasone in cultured renal papillary collecting duct cells. 1262 30

Alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion. It is one of the most prevalent skeletal muscle disorders in the Western hemisphere, affecting between 40% and 60% of all chronic alcohol misusers. However, the pathogenic mechanisms are unknown, although recent studies have suggested that membrane defects occur as a consequence of chronic alcohol exposure. It was our hypothesis that alcohol ingestion perturbs membrane-located proteins associated with intracellular signalling and contractility, in particular those relating to calcium homeostasis. To test this, we fed male Wistar rats nutritionally complete liquid diets containing ethanol as 35% of total dietary energy. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 6 weeks, rats were killed and skeletal muscles dissected. These were used to determine important ion-regulatory skeletal muscle proteins including sarcalumenin (SAR), sarcoplasmic-endoplasmic reticulum Ca(2+)-adenosine triphosphatase (ATPase) (SERCA1), the junctional face protein of 90 kd (90-JFP), alpha(1)- and alpha(2)-dihydropyridine receptor (alpha(1)-DHPR and alpha(2)-DHPR), and calsequestrin (CSQ) by immunoblotting. The relative abundance of microsomal proteins was determined by immunoblotting using the enhanced chemiluminescence (ECL) technique. The data showed that alcohol-feeding significantly reduced gastrocnemius and hind limb muscle weights (P <.05 in both instances). Concomitant changes included increases in the relative amounts of SERCA1 (P <.05) and Ca(2+)-ATPase activity (P <.025). However, there were no statistically significant changes in either SAR, 90-JFP, alpha(1)-DHPR or alpha(2)-DHPR (P >.2 in all instances). Reductions in CSQ were of marginal significance (P =.0950). We conclude that upregulation of SERCA1 protein and Ca(2+)-ATPase activity may be an adaptive mechanism and/or a contributory process in the pathology of alcohol-induced muscle disease.
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PMID:Ca2+-regulatory muscle proteins in the alcohol-fed rat. 1450 14

1. Administration of ethanol (14g/day per kg) for 21-26 days to rats increases the ability of the animals to metabolize ethanol, without concomitant changes in the activities of liver alcohol dehydrogenase or catalase. 2. Liver slices from rats chronically treated with ethanol showed a significant increase (40-60%) in the rate of O(2) consumption over that of slices from control animals. The effect of uncoupling agents such as dinitrophenol and arsenate was completely lost after chronic treatment with ethanol. 3. Isolated mitochondria prepared from animals chronically treated with ethanol showed no changes in state 3 or state 4 respiration, ADP/O ratio, respiratory control ratio or in the dinitrophenol effect when succinate was used as substrate. With beta-hydroxybutyrate as substrate a small but statistically significant decrease was found in the ADP/O ratio but not in the other parameters or in the dinitrophenol effect. Further, no changes in mitochondrial Mg(2+)-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg(2+)-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H(2)O(2)-producing system, was increased by 80-100% by chronic ethanol treatment. Oxidation of formate to CO(2)in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H(2)O(2) by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H(2)O(2) and oxidation of ethanol by the catalase system could not account for more than 10-20% of the increased ethanol metabolism in the animals chronically treated with ethanol. 5. Results presented indicate that chronic ethanol ingestion results in a faster mitochondrial O(2) consumption in situ suggesting a faster NADH reoxidation. Although only a minor change in mitochondrial coupling was observed with isolated mitochondria, the possibility of an uncoupling in the intact cell cannot be completely discarded. Regardless of the mechanism, these changes could lead to an increased metabolism of ethanol and of other endogenous substrates.
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PMID:Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity. 1674 11

1. Chronic ethanol administration to rats for 21-27 days increases the rate of O(2) consumption as measured in liver slices. The extra respiration can be abolished by inhibition of the active transport of Na(+) and K(+). Dinitrophenol activates the respiratory rate in the liver of the treated animals only in the presence of ouabain. 2. Active (ouabain-sensitive) transport of (86)Rb and (Na(+)+K(+))-stimulated adenosine triphosphatase activity were increased in the livers of the ethanol-treated animals. 3. Chronic ethanol administration also led to a decrease in the phosphorylation potential ([ATP]/[ADP][P(i)]) in the liver cell owing to a decrease in [ATP] and an increase in [P(i)]. 4. It is suggested that an increased sodium pump activity is responsible for the increased oxidative capacity and for the insensitivity to dinitrophenol observed in the livers of ethanol-treated animals.
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PMID:Metabolic alterations produced in the liver by chronic ethanol administration. Changes related to energetic parameters of the cell. 1674 12

1. Liver slices from rats treated with thyroxine show an increased rate of O(2) consumption. The extra consumption, but not the basal respiration, can be abolished by ouabain. 2. Dinitrophenol is not effective in increasing the rate of O(2) consumption of liver slices from thyroxine-treated animals but its effectiveness can be recovered in the presence of ouabain. 3. (Na(+)+K(+))-stimulated adenosine triphosphatase activity of liver was increased by administration of thyroxine in vivo. No changes were found in total Mg(2+)-stimulated adenosine triphosphatase activity. 4. Mitochondrial alpha-glycerophosphate dehydrogenase and microsomal NADPH oxidase activity were increased by both thyroxine and chronic ethanol treatment. 5. Liver slices from animals chronically treated with ethanol synthesize urea at an increased rate. 6. Mitochondrial size (section area) is markedly increased in the liver of animals chronically treated with ethanol. 7. Acute administration of ethanol in doses of 4 and 6g/kg significantly increases the uptake of (131)I-labelled thyroxine by the liver. 8. Work reported here, along with results from other investigators, indicates marked similarities between the effects produced in the liver by chronic administration of ethanol and by thyroid hormones.
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PMID:Metabolic alterations produced in the liver by chronic ethanol administration. Comparison between the effects produced by ethanol and by thyroid hormones. 1674 13


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