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)

We have studied a female mongrel dog found in Kanagawa Prefecture, Japan. This dog was selected and examined thoroughly because she naturally maintained a high glutathione (GSH) concentration in her erythrocytes and did not exhibit any clinical signs or hematologic disorders. Erythrocytes from this animal demonstrated high K and low Na concentrations, as well as accumulation of the amino acids, glutamic acid, aspartic acid and glutamine. The Na, K-ATPase activity was also markedly elevated and the osmotic fragility of the dog's erythrocytes was found to be significantly increased. Crossbreeding of our dog with a normal dog and also with a heterozygous carrier dog revealed that the genetic abnormality possessed by our dog is transmitted as an autosomal recessive trait. All of the clinical data obtained from studying this animal strongly suggest that it possesses a genetic trait similar to that of the HK dogs previously described by Maede.
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PMID:A dog possessing high glutathione (GSH) and K concentrations with an increased Na, K-ATPase activity in its erythrocytes. 284 Mar 4

The effects of HgCl2, CH3HgCl, p-chloromercuribenzene sulfonate (PCMBS), and CdCl2 on plasma membrane and cell metabolic functions of skate (Raja erinacea) hepatocytes in suspension culture were assessed by measuring (a) the rates of Na+-dependent and -independent L-[14C]alanine uptake, (b) Na+-dependent 86Rb+ uptake, a measure of Na-K-ATPase activity, (c) 86Rb+ efflux, a measure of K+ permeability, (d) the difference between the 3H2O and [14C]inulin distribution spaces, a measure of intracellular water volume, (e) cellular ATP concentrations, and (f) glutathione (GSH) and glutathione disulfide (GSSG) levels. The initial rates of L-alanine and 86Rb+ uptake were inhibited by each of these metals in the following order: HgCl2 greater than CH3HgCl greater than PCMBS greater than CdCl2. Inorganic mercury significantly inhibited the initial rates of Na+-dependent L-alanine and 86Rb uptakes at a concentration of 10 microM, whereas 100 microM produced nearly complete inhibition. These effects were dose-dependent, immediate (observed after less than 5 min of incubation with the metal), and persistent. Mercuric chloride also impaired volume regulatory mechanisms in skate hepatocytes: cells treated with 50 microM HgCl2 swelled slowly over a 60-min interval to volumes nearly double those of control cells. In addition, HgCl2 prevented the normal volume regulatory decrease observed after swelling the hepatocytes in hypotonic media. Mercuric chloride (5-50 microM) produced a rapid initial loss of a large fraction of intracellular 86Rb, followed by a slower rate of release of the remaining isotope. These effects were prevented if GSH was added with, but not following HgCl2. In contrast, dithiothreitol, a more permeable thiol, both prevented and even partially reversed the effects of mercury. Mercuric chloride (10 microM) had no effect on cellular ATP, GSH, or GSSG levels for up to 4 hr incubation. These findings indicate that 86Rb+ (K+) efflux is a sensitive indicator of mercury toxicity, and are consistent with the hypothesis that the plasma membrane is a primary target for mercury's effects. A change in membrane permeability to K+ would dissipate transmembrane electrochemical gradients, and may contribute to the apparent inhibition of transport processes energized by these gradients, such as Na+-alanine cotransport, and volume regulatory mechanisms.
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PMID:Altered plasma membrane ion permeability in mercury-induced cell injury: studies in hepatocytes of elasmobranch Raja erinacea. 284 8

The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.
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PMID:Effects of tannins on the oxidative damage of mouse ocular lens. I. Using the oxidative damage model induced by the xanthine-xanthine oxidase system. 284 23

The mechanisms of inhibition of rat brain Na+-K+-ATPase by cadmium chloride (CdCl2) and methylmercuric chloride (CH3HgCl) were studied in vitro by assessing the effects of these heavy metals on this enzyme and associated component parameters. Both the heavy metals significantly inhibited the overall Na+-K+-ATPase in a concentration-dependent manner with an estimated median inhibitory concentration (IC-50) of 3.2 X 10(-5) M for CdCl2 and 6 X 10(-6) M for CH3HgCl. Protection of enzyme against heavy metal inhibition by 5 X 10(-5) M to 1 X 10(-4) M dithiothreitol (DTT) and glutathione (GSH) or cysteine (CST) indicates that both monothiols and dithiols have the same ability in regenerating sulfhydryl (-SH) groups or chelating the metals. Inhibition of K+-p-nitrophenyl phosphatase (K+-PNPPase), the component enzyme catalyzing the K+-dependent dephosphorylation in the overall Na+-K+-ATPase reaction by these heavy metals, indicates that the mechanism of inhibition involves binding to this phosphatase. Reversal of K+-PNPPase inhibition by DTT, GSH, and CST suggests sulfhydryl groups as binding sites. Binding of 3H-ouabain, a cardiac glycocide and inhibitor of both phosphorylation and dephosphorylation, to brain fraction was significantly decreased by CH3HgCl, and this inhibition was reversed by the three thiol compounds, suggesting presence of -SH group(s) in the ouabain receptor site. Cadmium chloride failed to inhibit the binding of this receptor, indicating that the mechanics of inhibition of ATPase by CH3HgCl and CdCl2 are different from each other. The results suggest that the critical conformational property of enzyme common to both kinase (E1) and phosphatase (E2) is susceptible to CH3HgCl whereas only phosphatase is sensitive to CdCl2.
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PMID:Mechanism of inhibition of rat brain (Na+-K+)-stimulated adenosine triphosphatase reaction by cadmium and methyl mercury. 285 66

Acetaminophen is activated metabolically to yield reactive species that bind covalently to liver cell macromolecules. The extent of covalent binding correlates with the occurrence and severity of hepatic necrosis. We reported previously [J. O. Tsokos-Kuhn, E. L. Todd, J. B. McMillin-Wood and J. R. Mitchell, Molec. Pharmac. 28, 56 (1985)] that active Ca2+ accumulation of isolated liver plasma membranes is decreased 60-75% after a hepatotoxic dose of acetaminophen in vivo. We now report that the protein of isolated liver plasma membranes was substantially labeled with drug metabolites after administration of [3H]acetaminophen. There was no increase in passive membrane permeability that might cause diminished Ca2+ accumulation. Intravesicular volume and relative purity of the vesicle preparations after acetaminophen were not different from controls. However, (Ca2+,Mg2+)-ATPase, a possible biochemical expression of the Ca2+ pump, was decreased 31% (P less than 0.025) after acetaminophen treatment. ATPase activity in both control and treated groups was enhanced by isolating membranes in the presence of 5 mM reduced glutathione (GSH), but the effects of drug treatment were not reversed. A similar effect of GSH on Ca2+ accumulation was observed previously [J. O. Tsokos-Kuhn, E. L. Todd, J. B. McMillin-Wood and J. R. Mitchell, Molec. Pharmac. 28, 56 (1985)]. These data are consistent with a hypothesis wherein alkylation of membrane proteins by reactive acetaminophen metabolites is a factor in the onset of hepatic necrosis after acetaminophen. They are not consistent with an oxidative stress hypothesis where thiol S-thiolation of membrane components is postulated to produce altered membrane permeability or thiol-reversible alterations in membrane protein structure and enzymatic function.
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PMID:Alkylation of the liver plasma membrane and inhibition of the Ca2+ ATPase by acetaminophen. 296 3

Extracellular reduction of ferricyanide was exhibited by isolated Cuscuta protoplasts. A larger decrease in NADH than NADPH levels of the ferricyanide-treated protoplasts pointed to the major involvement of the former as an electron donor. Glutathione levels were also found to be lowered in similarly treated tissue. The time-dependent variation in intracellular ATP levels in presence of ferricyanide supported the concept of plasma membrane ATPase activation during transplasma membrane electron transport in eukaryotes.
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PMID:Changes in intracellular redox and energy status during induced transplasma membrane electron transport in Cuscuta protoplasts. 297 17

Brain (Na+ + K+)-ATPase was protected by low concentrations of GSH from the inhibitory effect of pyrithiamin. The possible involvement of sulfhydryl groups in the inhibition was then studied by comparing the effect of pyrithiamin with that of N-ethylmaleimide on the enzyme. The treatment of rat brain (Na+ + K+)-ATPase with thesee inhibitors caused a significant decrease in reactivity of the enzyme to N-ethyl[3H]maleimide. N-Ethylmaleimide, like pyrithiamin, inhibited the partial reactions of (Na+ + K+)-ATPase system in parallel with the inhibition of the overall reaction. An SDS-polyacrylamide gel electrophoresis procedure indicated that pyrithiamin and N-ethylmaleimide inhibited Na+-dependent phosphorylation of the alpha(+) form of rat brain (Na+ + K+)-ATPase more than that of alpha, though the selectivity for the alpha(+) seemed to be higher with the former inhibitor than in the latter. The treatment also decreased sensitivity of the enzyme to ouabain inhibition. However, pyrithiamin- and N-ethylmaleimide-induced inactivations of the enzyme differed in the efficacy of GSH for protection and in the effect of the kind of ligands present during the reaction. Furthermore, pyrithiamin did not appear to interact directly with sulfhydryl groups, but caused the formation of disulfide in bovine brain (Na+ + K+)-ATPase. In contrast to N-ethylmaleimide, pyrithiamin did not affect the sulfhydryl-enzymes such as alcohol dehydrogenase and L-alanine dehydrogenase. It is concluded that pyrithiamin modifies the functional sulfhydryl groups of brain (Na+ + K+)-ATPase in a way different from N-ethylmaleimide and causes a structural change and inactivation of the enzyme.
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PMID:Involvement of sulfhydryl groups in the inhibition of brain (Na+ + K+)-ATPase by pyrithiamin. 298 20

This study focused on whether changes in lens levels of glutathione and calcium, early events associated with cataract formation, were related or that one might cause the other. The first part of the investigation was concerned with the extent to which an increase in levels of intracellular calcium might alter GSH levels in lens fiber and epithelial cells. The results demonstrate that calcium accumulation, either at 19 degrees C or 37 degrees C, did not diminish the concentration of GSH. More importantly, GSH levels did not decline in opaque regions of a calcium-loaded lens. The reciprocal part of the problem focused on whether a decline in lens thiol might lead to an increase in levels of calcium and subsequent opacification. In particular, it was shown that treatment of lenses with parachloromercuribenzene sulphonic acid (PCMBS), a nonpenetrating sulphydryl probe, resulted in a 10-30% loss of membrane SH groups in the epithelium. Diminished numbers of SH groups was accompanied by chloride fluxes and an increase in membrane permeability to sodium and calcium with an influx of sodium and calcium leading to opacities. It is important to note that these changes occurred in the absence of any change in cellular levels of soluble protein-SH or GSH. Additional experiments suggest that calcium transport was not impaired, as evidenced by lack of inhibition of Ca-ATPase activity in lenses treated with PCMBS. The results suggest that one explanation for opacification is that oxidative insults, which diminish GSH levels, leads to a loss of important membrane SH groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The importance of membrane sulfhydryl groups to calcium homeostasis in the lens. 299 53

The response of the poikilothermal lens to various incubation temperatures in vitro was compared with that of the homothermal lens. The rainbow trout lens was used as the poikilothermal lens and the rat lens as the homothermal lens. In contrast to rat lenses, cataract developed at 37 degrees C in rainbow trout lenses, which was called 'warm cataract'. Warm cataract developed not only when lenses were incubated in vitro but also when rainbow trout were kept in water at 37 degrees C. Water, Na+, Ca2+ and insoluble protein increased and K+ and Mg2+ decreased in warm cataract lenses, but GSH and soluble protein sulfhydryl levels did not change. This cataract was irreversible after only 5 min incubation at 37 degrees C. On the other hand, rainbow trout lenses remained transparent without the change of cation balance at 0-25 degrees C while cold cataract developed in rat lenses. Na,K-ATPase activity was detected at 0 degrees C in rainbow trout lens homogenates, but not in rat lens homogenates. Na+-K+ ratio (Na+/K+) increased when the rainbow trout lens was treated with ouabain at 0 degrees C. In the rainbow trout lens, lactic acid was produced continuously for 30 days at 0 degrees C while it was not in the rat lens between 1 hr and 10 days after. These results strongly suggest that Na,K-ATPase acts as a cation pump at 0 degrees C and that ATP is supplied by glycolysis in the rainbow trout lens in order to maintain the transparency. The above results also suggest that enzymes and membrane structures in rainbow trout lens are adapted to a cold-temperature habitat and that Na,K-ATPase and anaerobic glycolysis are important for the maintenance of lens transparency at low temperatures.
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PMID:Studies on the eye lens in poikilothermal animals. I. Comparative studies on cation maintenance systems in rainbow trout and rat lenses. 299 50

Decreased glutathione levels in the ocular lens have been invoked as a possible cause for the decreased lenticular Na+-K+-ATPase in diabetes because both are corrected by aldose reductase inhibitors, and the Na+-K+-ATPase is known to be susceptible to oxidation inactivation. Because an analogous Na+-K+-ATPase defect that is prevented by aldose reductase inhibitors has been described in diabetic peripheral nerve, we examined the effect of streptozocin (STZ) diabetes and aldose reductase inhibition on reduced (GSH) and oxidized (GSSG) glutathione levels in crude homogenates of rat sciatic nerve. Neither GSSG nor GSH levels were altered by 2 or 8 wk of untreated diabetes or by aldose reductase inhibition. Because the defect in Na+-K+-ATPase is fully expressed by 4 wk of STZ diabetes, we conclude that altered glutathione redox state plays no detectable role in the pathogenesis of this defect in diabetic peripheral nerve.
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PMID:Glutathione redox state is not the link between polyol pathway activity and myo-inositol-related Na+-K+-ATPase defect in experimental diabetic neuropathy. 301 9


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