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)

Basolateral membranes from rabbit proximal colon were prepared from isolated colonocytes throughout postnatal maturation, using a modification of published techniques. In suckling (14-20 day) and post-weaning/mature (35-49 day) animals, membranes were purified approx. 10-fold, based upon the enrichment of ouabain-sensitive, sodium-potassium dependent adenosine triphosphatase activity. Membrane lipid analyses demonstrated age-dependent increases in total cholesterol and the cholesterol/phospholipid molar ratio, as well as decreases in phosphatidylethanolamine content and the fatty acid unsaturation index. Fluidity of basolateral membranes and membrane liposomes, determined from fluorescence anisotropy measurements using the lipid probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, demonstrated significant, ontogenic decreases in fluidity; and, additional studies showed that fluidity changes occurred early in the weaning period (by day 24 postnatally). Arrhenius plots of liposome anisotropies suggested a bilayer lipid thermotropic transition temperature of 22 degrees C in sucklings 26 degrees C in mature rabbits. These findings demonstrate that ontogeny of colonic basolateral membranes is associated with significant modulations in lipid composition and fluidity.
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PMID:Ontogeny of proximal colon basolateral membrane lipid composition and fluidity in the rabbit. 161 27

Rats were maintained on nutritionally complete diets enriched in unsaturated (corn oil) or saturated (butter fat) triacylglycerols. After 6 weeks, significant differences in the lipid composition and fluidity of a number of intestinal membranes were observed. The corn oil diet (enriched mainly in linoleic acid) increased the overall unsaturation of the acyl chains and enhanced the lipid fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, of enterocyte microvillus and basolateral membranes and of colonocyte basolateral membranes. Concomitantly, the cholesterol content and the cholesterol/phospholipid molar ratio were increased in the microvillus but not in the basolateral membranes. The increased cholesterol in ileal microvillus membranes can result from enhanced cellular biosynthesis, since ileal slices from rats fed the unsaturated diet incorporated [14C]octanoate more rapidly into digitonin-precipitable sterol. Increased fluidity of the enterocyte microvillus and basolateral membranes, respectively, enhanced the enzyme specific activities of p-nitrophenylphosphatase and (Na+ + K+)-dependent adenosine triphosphatase. The results indicate that the lipid composition, fluidity and enzyme activities of intestinal plasma membranes can be altered by dietary means. Moreover, rat enterocytes possess regulatory mechanisms which modulate the cholesterol content of the microvillus membranes so as to mitigate changes in lipid fluidity.
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PMID:Variations in dietary triacylglycerol saturation alter the lipid composition and fluidity of rat intestinal plasma membranes. 396 22

Inhibition of renal Na+,K+-adenosine triphosphatase is an early biochemical manifestation of gentamicin treatment in rats. Studies with isolated, perfused rat kidneys in filtering and nonfiltering modes indicate that gentamicin is transported across the brush border membrane before enzyme inhibition. The drug caused enzyme inhibition (42%) only in filtering kidneys, and this inhibition was blocked by spermine, an inhibitor of gentamicin binding. In purified rat renal basolateral membranes, bound [3H]gentamicin was displaced 88% by unlabeled gentamicin. After in vivo exposure to [3H]gentamicin, the radioactivity associated with the isolated basolateral membranes was displaced only 46% by unlabeled drug. These results suggest that inhibition of renal Na+,K+-adenosine triphosphatase by gentamicin is probably due to an interaction at the cytoplasmic face of the basolateral membrane. Scatchard plots of [3H]gentamicin binding to basolateral and brush border membranes revealed a single class of noninteracting sites in each membrane. Gentamicin did not change the bulk membrane lipid fluidity, as estimated by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene.
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PMID:Inhibition of renal Na+, K+-adenosine triphosphatase by gentamicin. 609 9

The effects of modifications in the cholesterol and fatty acid contents of membranes on the transport of potassium have been studied in Mycoplasma mycoides subspecies capri. A decrease in the cholesterol content from 110 micrograms/mg of membrane protein to less than 10 micrograms/mg of membrane protein is associated with a decrease in the level of intracellular potassium from 40 micrograms of K/mg of protein to 23 micrograms of K/mg of cell protein. Replacement of oleate plus palmitate by elaidate alone in the growth medium has only limited effects on the intracellular K content. In metabolizing cells, 42K influxes were 0.42, 0.65, and 0.69 micrograms of K/mg of cell protein per min for cholesterol-rich cells supplemented with elaidate or with oleate plus palmitate and for cells adapted to low cholesterol and supplemented with elaidate, respectively. This increase in influx was associated with an increase in membrane fluidity as determined by fluorescence polarization experiments in which 1,6-diphenyl-1,3,5-hexatriene was used as a probe. For elaidate-supplemented cells, examination of the temperature dependence of 43K influx revealed the existence of a break or a discontinuity at temperatures corresponding to modifications in the physical state of the membrane. The lack of correspondence between the patterns of K+ influx and the Mg++-adenosine triphosphatase (ATPase) activity indicates that the sensitivity of this influx to the physical state of the membrane is not attributable to the Mg++-ATPase but likely reflects an effect of membrane lipids on the K+ carrier itself.
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PMID:Recent developments in the study of potassium transport in Mycoplasma mycoides subspecies capri. 612 24

The lipid composition and fluidity of basolateral membranes prepared from the mucosa of the proximal, middle and distal thirds of the rat small intestine were determined. Fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and a series of anthroyloxy fatty acid derivatives, is decreased in the distal third as compared to the proximal segments. This pattern is similar to that described previously for microvillus membranes. The decrease in fluidity of the distal as compared to the proximal membranes results from an increase in cholesterol content, cholesterol/phospholipid molar ratio and degree of saturation of the fatty acid residues. In the middle and distal thirds of the gut, the degree of saturation of the fatty acid residues is higher in microvillus as compared to basolateral membranes, accounting in part for the characteristically lower fluidity of the luminal membranes. The specific activity of the basolateral membrane (Na+ + K+)-dependent adenosine triphosphatase is significantly lower in the distal as compared to the proximal and middle thirds of the intestinal mucosa. Studies of the binding of [3H]ouabain indicate that this pattern results from fewer enzyme sites in the distal membranes.
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PMID:Lipid composition and fluidity of rat enterocyte basolateral membranes. Regional differences. 632 92

The isolation of basolateral membranes from rat proximal colonic epithelial cells is described. Cells were harvested using a technique combining chelation of divalent cations with mechanical dissociation. After homogenization, differential centrifugation yielded a 'crude' membrane fraction which was further purified using sucrose density centrifugation. The final membrane fraction was enriched 10-14-fold over homogenate in ouabain-sensitive sodium-potassium dependent adenosine triphosphatase and ouabain-sensitive potassium-dependent phosphatase specific activities. SDS-polyacrylamide gel electrophoresis of this membrane revealed at least 18 protein bands with molecular weights of 14600-200000. Phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, free cholesterol and fatty acids were the major lipid components of this membrane. The predominant fatty acids were palmitic (16:0), oleic (18:1), stearic (18:0) and linoleic (18:2) acid. Membranes and their liposomes were studied, using the lipid soluble fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH), by steady-state fluorescence polarization. The fluorescence anisotropy was greater in the intact membranes compared to their liposomes, indicating greater fluidity in the liposomes. Compositional studies suggested that the high fluidity of this membrane was due to its low ratios of protein/lipid (w/w), cholesterol/phospholipid (mol/mol), and sphingomyelin/phosphatidylcholine (mol/mol).
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PMID:Isolation and partial characterization of basolateral membranes from rat proximal colonic epithelial cells. 683 Jul 71

Physical-chemical-activity relationship of aromatic hydrocarbons (n = 10) and alkyl acetates (n = 16) with respect to their in vitro effects on synaptosomal membranes was studied. Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity and membrane fluidity, which was determined using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene, were used as potential indicators of neuronal cell toxicity. The potency of inhibition for the enzyme (IC50), the potency of increasing membrane fluidity (IC12.5), and n-octanol/water partition coefficient (P) were all determined experimentally for 26 solvents. Correlation analyses were made on aromatic hydrocarbons and on alkyl acetates. There were linear relationships between log P and pIC50 (log1/IC50) values, and between log P and pIC12.5 (log1/IC12.5) values, indicating that the hydrophobicity of the solvents determines their toxic ability to affect membrane environment; the more hydrophobic the solvents are, the more toxic they are. A direct linear relationship between Na(+)-K(+)-ATPase activity pIC50 and membrane fluidity pIC12.5 values was also shown. This predictive correlation suggests a similar mechanism of membrane surface interaction govering both processes that are common to the test solvents. The present results confirm the importance of the lipid environment of neuronal membranes in maintaining the normal function of membrane-bound protein.
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PMID:Physical-chemical-activity relationship of organic solvents: effects on Na(+)-K(+)-ATPase activity and membrane fluidity in mouse synaptosomes. 786 56

The structure-toxicity relationship of monoketones, a class of organic solvents widely used in industry, was investigated with respect to their in vitro effects on synaptosomal membrane proteins. The toxic parameters used were Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase), a well-known marker enzyme often used as a membrane toxicity model, and 3H-dihydroalprenolol (3H-DHA)-labeled beta-adrenergic receptor binding that has been shown to be vulnerable to solvent-induced changes in membrane fluidity. In vitro treatments with 12 kinds of monoketones (carbon chain length from 3-10) dose-dependently inhibited both 3H-DHA binding to mouse synaptosomes and Na(+)-K(+)-ATPase activity. The potency of inhibition (IC50) for both the two parameters was linearly related to n-octanol/water partition coefficient and synaptosome/buffer partition coefficient of the test compounds. Additions of monoketones did not significantly alter the number of 3H-DHA binding sites but markedly decreased their affinity. In each monoketone, the IC50 values for 3H-DHA binding and Na(+)-K(+)-ATPase activity were generally within the same range. The anisotropy of fluorescence probe 1,6-diphenyl-1,3,5-hexatriene-labeled synaptosomal membranes was dose-dependently decreased by the monoketones, implying increased membrane fluidity. These results indicate that increasing lipophilicity of monoketones results in increased solvent penetration of synaptic membrane preparations, leading to conformational changes in membrane structure and increased ability to inhibit both neuroreceptor binding and enzyme activity. The present data confirm the importance of the lipid micro-environment of membranes in maintaining the normal functions of membrane-bound proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure-toxicity relationship of monoketones: in vitro effects on beta-adrenergic receptor binding and Na(+)-K(+)-ATPase activity in mouse synaptosomes. 827 28

The in vivo anesthetic activity of monoketones in mice was examined in relation to their hydrophobicity and to the in vivo effects on Na+/K+ -adenosine triphosphatase (Na+/K+ -ATPase) activity and membrane fluidity. Anesthetic potency (AD50) of monoketones was determined; AD50 implys the dose required to anesthetize 50% of the animals from the treated group. The n-octanol/water partition coefficient (P) was used as an index of hydrophobicity. Membrane fluidity was determined by using 1,6-diphenyl-1,3,5-hexatriene (DPH) or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH as fluorescence probes. Log (1/AD50) was the parabolic function of log P, log ((1/AD50) = -0.167(log P)2 + 0.698 log P - 1.365, and the log P that corresponds to the minimum AD50 was estimated to be 2.09. Brain synaptosomes were prepared from mice that were considered anesthetized with each of the 4 monoketones (1.5-fold AD50), methyl n-propyl, methyl n-amyl, methyl 3-methylhexyl and methyl n-octyl ketone. The Na+/K+ -ATPase activity was inhibited by methyl n-propyl ketone alone, membrane DPH fluidity was decreased by each of the 4 monoketones, and membrane TMA-DPH fluidity was decreased by methyl n-propylketone alone. These results suggest an involvement of the decreased DPH fluidity in monoketone-induced anesthesia.
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PMID:Anesthetic activity of monoketones in mice: relationship to hydrophobicity and in vivo effects on Na+/K+ -ATPase activity and membrane fluidity. 861 59

The causes of the reduced activity of Na+/K+-adenosine triphosphatase (ATPase) in human diabetes are still the object of controversy. The aim of this work was to investigate the mechanisms of inhibition by means of the study of the Na+/K+-ATPase purified from human placenta. We purified Na+/K+-ATPase from term placentas of six healthy women and six age-matched women with insulin-dependent diabetes mellitus (IDDM) in good metabolic control. The enzymatic activity was reduced in both the microsomal fraction and the purified Na+/K+-ATPase obtained from diabetic women, whereas no difference was found in the number of active molecules determined by anthroyl ouabain binding. The Na+/K+-ATPase purified from women with IDDM did not show any modification in the ouabain affinity or changes in the physicochemical structure of the ouabain binding site investigated by dynamic fluorescence or alterations in lateral diffusion. The activation energy of the enzyme was increased, whereas the tryptophan accessibility of the enzyme was lower in women with IDDM. The fluidity of the lipid anulus of the enzyme was higher in women with IDDM than in control women, as suggested by fluorescence polarization of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene. The adenosine triphosphate-binding site, investigated by anisotropy decay studies of the fluorescent probe pyrene isothiocyanate, was modified in women with IDDM. It appears that the Na+/K+-ATPase of human placenta is altered in its disposition in IDDM.
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PMID:Modifications induced by insulin-dependent diabetes mellitus on human placental Na+/K+-adenosine triphosphatase. 935 71


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