Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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)
 ...
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.
 ...
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.
 ...
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

Rabbit corneas were isolated, denuded of epithelium, and perfused on the anterior and posterior surfaces with Krebs Ringer-bicarbonate with additions of 50 microM H2O2, 125 microM BCNU, or 100 microM ouabain. The permeability of the corneal endothelium to labelled mannitol and inulin was determined by adding these compounds to the endothelial perfusate and measuring the rate of appearance of radioactivity in the anterior perfusate. Both H2O2 and BCNU increased the flux of mannitol and inulin across the endothelium in a time dependent manner, but ouabain had no effect. Additions of glucose with H2O2 or of GSH with BCNU prevented the observed changes in permeability. ATPase activities in the endothelia of intact, isolated corneas were also determined following incubation in the same media. The only observable effects of H2O2 and BCNU were slight reductions in the activity of Na+ + K+ ATPase. It is concluded that permeability changes, the leak, are more critical than active transport processes, the pump, in determining the rate and extent of swelling that results from exposure of the cornea to these agents.
 ...
PMID:Pump and leak in regulation of fluid transport in rabbit cornea. 316 May 43

The protective effect of geraniin (tannin from Geranium thunbergii) against oxidative damage was examined in the mouse ocular lens. Oxidative damage in the lens was induced by diamide, diazene dicarboxylic acid bis (N,N-dimethylamide); diamide oxidized the sulfhydryl groups in both the membrane and cytoplasm but did not increase lipid peroxide. Geraniin showed protective effects on the changes in the Na+/K+ ratio, GSH level, Na,K-ATPase activity, GSH reductase activity and the sulfhydryl level of the membranous protein in the diamide-treated lens, but such protective effects of geraniin were not observed in the cell-free system of the lens. In addition, geraniin itself was unable to reduce GSSG to GSH and also unable to inhibit the oxidative reaction of the sulfhydryl group to diamide. These results suggest that in the intact lens geraniin would act primarily on the lens cell membrane surface to inhibit an influx of diamide into the inner part of the plasma membrane and the cytoplasm, and consequently that geraniin may protect sulfhydryl groups in the cell membrane and cytoplasm from their oxidation by diamide and keep the redox system of the lens in a normal state.
 ...
PMID:Effect of tannin on oxidative damage of ocular lens. 318 50

The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70-90% led to a decrease in uptake and increase in efflux of 86Rb. ATP levels and Na+/K+-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na+/K+-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H2O2 showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na+/K+ pump, thus leading to ionic changes and cataract development.
 ...
PMID:Effect of glutathione depletion on cation transport and metabolism in the rabbit lens. 318 92

The effects of the SH-groups binding agent p-chloromercurybenzoate (rho CMB) and the SH-containing compounds dithiothreitol (DTT), beta-mercaptoethanol (ME) and reduced glutathione (GSH) on activation by Mg2+ and K+ of ATPase in plasma membrane preparations from corn sprout root cells were studied. Rho CMB inhibited the ATPase activity, the degree of inhibition being directly dependent on the increase of the inhibitor concentration (from 10(-6) up to 10(-4) M); the inhibition was eliminated by the SH-containing agents (25 mM). DTT and ME added to the homogenization medium and ME added to the reaction mixture produced different effects on the ATPase activity of the membranes depending on the nature of the cations added. In the absence of the additives the ATPase activity was somewhat decreased, showing a sharp rise in the presence of Mg2+; an addition of K+ to a Mg2+-containing medium further increased the enzyme activity. GSH had no effect on the ATPase activation by the cations.
 ...
PMID:[The role of SH-groups in the development sensitivity of ATPase in plasma membranes of plant cells to ions]. 621 85

Intoxication of rats with paracetamol (2.0 g/kg, b. wt.,os) is not followed by peroxidative decomposition of liver microsomal lipids "in vivo" but seems to interfere with ATPase and 5'-Nucleotidase activity in isolated plasmamembranes. Treatment with reduced glutathione, cys=teine and 2. mercaptopropionylglycine results in partial protection against liver injury provoked by the toxin. However, these sulphydryl compounds are not able to prevent the fall of liver GSH content occurring after paracetamol.
 ...
PMID:[Susceptibility of the liver to lipid peroxidation after treatment with paracetamol]. 626 99

The mammalian lens contains an unusually high concentration of glutathione (GSH), the highest level being in the epithelium. GSH is present largely in the reduced state. The high concentration of GSH in a normal lens and the decreased concentration in most types of cataracts have led to many hypotheses on its role in cataract formation. These hypotheses are considered in the light of current evidence. GSH is synthesized and degraded in the lens. Both processes require ATP, derived largely from glycolysis. Carbohydrate metabolism is also involved in the maintenance of GSH in the reduced state. There is a direct link between the rate of formation of oxidized glutathione (GSSG) and the stimulation of the hexose monophosphate shunt through the generation of NADPH. One possible function of GSH in the lens is to maintain the thiol (SH) groups of proteins in the reduced state, thus preventing formation of high molecular weight (HMW) protein aggregates. The formation of HMW proteins in X-ray-induced cataracts through disulphide bond formation and the involvement of SH oxidation in HMW proteins isolated from human cataractous lenses suggest a role for GSH in protecting protein SH groups. GSH in the lens may also protect critical SH groups involved in regulating cation transport and permeability. Studies with mammalian lenses indicate that lowering the lens GSH concentration leads to increased permeability to cations and inactivation of Na+,K+-ATPase. A consequence of the changes in ion distribution is the inhibition of protein synthesis, which may explain the cessation of growth in cataractous lenses. GSH may also protect against oxidative damage to the lens. GSH metabolism is intimately involved in detoxification of H2O2, normally present in the aqueous humour. Lenses with impaired shunt activity or inhibited glutathione reductase are more susceptible to oxidative damage by peroxide. This may contribute to the formation of cataract.
 ...
PMID:Metabolism and function of glutathione in the lens. 656 81


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