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)

The effect of acrylonitrile (VCN) on erythrocyte lipid metabolism was investigated in vitro in metabolically active red cells from male Sprague-Dawley rats containing three types of hemoglobins: oxyhemoglobin, methemoglobin, and carbon monoxyhemoglobin. VCN at the concentration of 10 mM rapidly depleted erythrocyte glutathione (GSH) (75% of control) and induced lipid peroxidation (274% of control). Degradation of oxy- and methemoglobin was directly proportional to the extent of lipid peroxidation (r = 0.89). Addition of glucose to the incubation medium decreased hemoglobin degradation while it slightly increased VCN-induced lipid peroxidation. The highest amount of lipid peroxidation occurred in erythrocytes containing carbon monoxyhemoglobin and glucose. In the isolated red cell membranes incubated with 10 mM VCN, the lipid peroxidation was 400% of controls. VCN (25 mM) noncompetitively inhibited erythrocyte membrane Na+/K(+)-ATPase activity and the degree of inhibition was inversely proportional to the reaction temperature (r = -0.88). These findings indicate that the VCN induced hemoglobin degradation and lipid peroxidation are two extremes of a spectrum of oxidative damage in red cells leading to a change in physical state of membrane structure causing inhibition of adenosine triphosphate (ATPase) activity.
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PMID:Hemoglobin degradation, lipid peroxidation, and inhibition of Na+/K(+)-ATPase in rat erythrocytes exposed to acrylonitrile. 196 27

Treatment of washed erythrocytes with tert-butyl hydroperoxide (0.5 mM, 10 min) inhibited basal Ca2+ + Mg2+-ATPase activity by 40% and calmodulin-stimulated activity by 54%. The inhibition was accompanied by the formation of methemoglobin and the aggregation of some membrane proteins into a high-molecular-weight polymer. Membranes, isolated from washed erythrocytes, showed a similar pattern of inhibition. Basal Ca2+ + Mg2+-ATPase activity was inhibited 50% at 10 min and 70% at 30 min while calmodulin-stimulated activity was inhibited 70% at 10 min and 84% at 30 min. Thiobarbituric acid-reactive products formed slowly during the first 10 min and then increased sharply between 10 and 30 min. The polymerization of membrane proteins was also observed during the tert-butyl hydroperoxide exposure. Inhibition of erythrocyte membrane enzymes was selective. The Na+ + K+-stimulated Mg2+ ATPase, like the Ca2+ + Mg2+-ATPase, was sensitive to membrane oxidation but the activities of Mg2+-ATPase and acetylcholinesterase were less inhibited by tert-butyl hydroperoxide. Acetylcholinterase was found to be very resistant to hydroperoxide treatment with less than 10% loss of activity. The effects of two other hyproperoxides on enzyme inhibition were studied also. Cumene hydroperoxide (0.5 mM) was found to be as potent as tert-butyl hydroperoxide but hydrogen peroxide at 10 mM did not produce thiobarbituric acid-reactive products or inhibit Ca2+ + Mg2+-ATPase activity until after 20 min. The selective effects of peroxides on these enzyme activities are discussed.
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PMID:Hydroperoxides selectively inhibit human erythrocyte membrane enzymes. 252 25

Methemoglobin formation and reduction in canine erythrocytes with inherited high Na,K-ATPase activity (HK cells) were compared with those in normal canine cells (LK cells). Nitrite-induced methemoglobin formation in hemoglobin solutions indicated that the hemoglobin from HK cells was oxidized at essentially the same rate as that of LK cells. However, methemoglobin formation in HK cells was slower due to the inhibition by high glutathione (GSH) concentration. Methemoglobin reduction was allowed to take place on nitrite-treated and washed erythrocytes in a glucose medium and was reduced more rapidly in HK cells than in LK cells. During the reduction, the amounts of lactate and pyruvate increased more rapidly in HK cells, indicating enhanced glycolysis in HK cells. It is thus evident that the hemoglobin of HK cells is more securely protected from nitrite-induced oxidation by the GSH presence in great excess and by the increase in glycolysis.
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PMID:Methemoglobin formation and reduction in canine erythrocytes with inherited high Na,K-ATPase activity. 255 75

Hemorrhage within the central nervous system (CNS) may be associated with subsequent development of seizure states or paralysis. Prior investigations indicate that hemoglobin, released from extravasated erythrocytes, may be toxic to the CNS by promoting peroxidation of lipids and inhibition of Na,K-ATPase. These deleterious effects are blocked both in vitro and in vivo by the Fe3+ chelator, desferrioxamine, indicating the involvement of free iron derived from hemoglobin. We now report that the Fe2+ chelator, ferene, also inhibits methemoglobin- and ferric iron-mediated CNS lipid oxidation, reflecting the reduction of Fe3+ by some component of the CNS. This reduction is apparent in the accumulation of the highly chromophoric ferene: Fe2+ chelate after the addition of Fe3+ salts to supernatants of murine brain homogenates. Because large amounts of ascorbic acid occur in mammalian CNS, we suspected that this reducing substance might be responsible. Indeed, the peroxidative effects of hemoglobin and iron on murine brain are blocked by washing of CNS membranes or by preincubation of crude homogenates with ascorbate oxidase. Furthermore, the addition of ascorbate to washed CNS membranes fully restores hemoglobin/iron-driven peroxidation. We conclude that posthemorrhagic CNS dysfunction may stem from damaging redox reactions between hemoglobin iron, ascorbic acid, and oxidizable components of the nervous system.
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PMID:Hemoglobin-mediated oxidant damage to the central nervous system requires endogenous ascorbate. 284 56

Effect of potassium gluconate (K-GL) on K+ uptake of rat erythrocytes was investigated. K-GL produced a significant increase in active K+ transport of Na+-rich erythrocytes, while Na+,K+-ATPase activity of hemoglobin-free ghosts without a glycolytic system was unaffected. When the experiment was carried out in intact erythrocytes, K-GL increased the lactate production and ATP content, and it promoted the methemoglobin reduction rate. In Na+-rich erythrocytes, the glycolysis inhibitors which produced a marked reduction in lactate content abolished the K-GL-induced increase in K+ and ATP content without affecting the KCl-induced increase. These results suggest that K-GL enhances K+ transport of erythrocytes through acceleration of glycolytic process.
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PMID:Effect of potassium gluconate on potassium transport of rat erythrocytes. 293 46

This study on erythrocytes in hemoglobin H (Hb H) disease reveals that unstable Hb H is bound to membranes to a greater extent, especially when it forms methemoglobin or is precipitated as inclusion body. The methemoglobin content of these erythrocytes is elevated in spite of a higher activity of NADH-methemoglobin reductase. The ATPase activity is doubled, and the ATP is presumably used for phosphorylation of membrane proteins, which leads to cross-linking of membrane proteins. This assumption could be supported by the observed decrease in non-electrolyte permeability, by increased binding of hemoglobin to the membrane and by polymerisation of membrane proteins detected by SDS-polyacrylamide gel electrophoresis. By means of electron microscopy, it could also be shown that the inclusion bodies are bound to the inner surface of membrane and cause its protrusion. This linkage might be responsible for the observed inhibition of the lateral movement of intramembrane particles.
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PMID:Erythrocyte alterations in hemoglobin H disease. 627 17

Copper(II) complexes were encapsulated in human red blood cells in order to test their possible use as antioxidant drugs by virtue of their labile character. ESR spectroscopy was used to verify whether encapsulation in red blood cells leads to the modification of such complexes. With copper(II) complexes bound to dipeptides or tripeptides, an interaction with hemoglobin was found to be present, the hemoglobin having a strong coordinative site formed by four nitrogen donor atoms. Instead, with copper(II) complexes with TAD or PheANN3, which have the greatest stability. ESR spectra always showed the original species. Only the copper(II) complex with GHL gave rise to a complicated behavior, which contained signals from iron(III) species probably coming from oxidative processes. Encapsulation of all copper(II) complexes in erythrocytes caused a slight oxidative stress, compared to the unloaded and to the native cells. However, no significant differences were observed in the major metabolic properties (GSH, glycolytic rate, hexose monophosphate shunt, Ca(2+)-ATPase) of erythrocytes loaded with different copper(II) complexes, with the exception of methemoglobin levels, which were markedly increased in the case of [Cu(GHL)H-1] compared to [Cu(TAD)]. This latter finding suggests that methemoglobin formation can be affected by the type of complex used for encapsulation, depending on the direct interaction of the copper(II) complex with hemoglobin.
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PMID:Copper(II) complexes encapsulated in human red blood cells. 759 66

It is established that acetaminophen exhibits oxidative behaviour. The effects of acetaminophen (0.3-14.5 microM) on methemoglobin levels, superoxide dismutase and Na(+)-K+ ATPase activities of normal and vitamin E or vitamin C pretreated erythrocytes were investigated. In acetaminophen incubated erythrocytes, methemoglobin concentration and superoxide dismutase activity were increased in a dose and incubation-time dependent manner, the activity of Na(+)-K+ ATPase was decreased by acetaminophen treatment. Vitamin E (1mg/dl of erythrocyte suspension) or vitamin C (1mg/dl of erythrocyte suspension) provided partial protection of hemoglobin, superoxide dismutase and Na(+)-K+ ATPase against acetaminophen action. Vitamin E was more effective than vitamin C.
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PMID:Effects of acetaminophen on methemoglobin, superoxide dismutase and Na(+)-K+ ATPase activities of human erythrocytes. 762 22

Human neutrophils, activated by phorbol myristate acetate in the presence of intact red blood cells (RBCs), caused inhibition of the Ca2+ pump ATPase of the RBCs and fragmentation of the enzyme as well as other membrane proteins. Inhibition of the Ca2+ pump ATPase of intact RBCs was directly related to the neutrophil concentration and the time of incubation. Ca2+ pump ATPase activity was partially protected by the addition of exogenous glutathione-glutathione peroxidase, but not by superoxide dismutase. The addition of sodium azide, a potent inhibitor of endogenous RBC catalase, enhanced inhibition of the Ca2+ pump ATPase of intact RBCs. Examination by SDS-polyacrylamide gel electrophoresis of membrane proteins isolated from RBCs preincubated with activated neutrophils showed gross changes in banding patterns as compared to controls. Thus, a significant amount of methemoglobin appeared to be associated with the membrane proteins, and, in general, protein bands appeared to be more diffuse and less defined than proteins in control lanes. In addition, there was an increase in the low molecular weight protein bands. Using a monoclonal antibody to the Ca2+ pump ATPase, it was shown that the 140 kDa band representing the Ca2+ pump ATPase decreased, with concomitant appearance of two low molecular weight bands running at 8.2 and 6.8 kDa in the membrane proteins from RBCs preincubated with activated neutrophils. The data are interpreted to suggest that inhibition of the Ca2+ pump ATPase in intact RBCs under these conditions occurred as a result of: neutrophil-derived superoxide, dismutation of superoxide, to H2O2, diffusion of H2O2 into RBCs, a Fenton type reaction between oxyhemoglobin, and H2O2 producing hydroxyl radical and/or a ferryl radical capable of promoting protein fragmentation of RBC membrane proteins, including the plasma membrane Ca2+ pump ATPase.
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PMID:Inhibition by activated neutrophils of the Ca2+ pump ATPase of intact red blood cells. 775 Jul 90

Incubation of human red blood cells (RBCs) with t-butyl hydroperoxide (tBHP) resulted in inhibition of the Ca-pump ATPase. This was demonstrated using an assay of the Ca-pump ATPase activity in intact RBCs. In this assay, activity of the Ca-pump ATPase is expressed as the rate constant of the initial loss of ATP in RBCs exposed to Ca and A23187. Pseudo-first-order rate constants (Ca-pump ATPase rate constants) were lower in the presence of tBHP versus controls. Incubation of RBCs with tBHP resulted in both a time- and concentration-dependent inhibition of the Ca-pump ATPase (IC50 approximately 1 mM). Incubation of RBCs with tBHP also resulted in decreased oxyhemoglobin, increased methemoglobin and increased thiobarbituric acid reactive substances (TBARS). GSH levels were significantly lower in the presence of tBHP. GSH fell from a control value of 2.2 mmol/l RBC to 0.46 mmol/l RBC after incubation with 0.25 mM tBHP for 15 min. Both butylated hydroxytoluene and stobadine prevented the formation of TBARS and were partially effective in protecting the Ca-pump ATPase from tBHP-induced inhibition. Dithiothreitol was completely effective in preventing the tBHP-induced formation of TBARS as well as inhibition of the Ca-pump ATPase. However, when added after exposure to tBHP, dithiothreitol was unable to restore Ca-pump ATPase activity completely. An activity of dithiothreitol independent of enzymic thiol group reduction was apparent. In the presence of mercaptosuccinate, a potent inhibitor of glutathione peroxidase, the ability of dithiothreitol to protect the Ca-pump ATPase from tBHP-induced inhibition was abolished. Therefore, protection by dithiothreitol may be afforded by its ability to replenish GSH from oxidized glutathione, thus allowing glutathione peroxidase to metabolize tBHP. These results may be interpreted to suggest that inhibition of the Ca-pump ATPase in intact RBCs occurs as a result of tBHP-induced oxidant stress and subsequent lipid peroxidation which can be prevented by certain antioxidants including butylated hydroxytoluene, stobadine, and thiol-containing compounds such as dithiothreitol. These findings provide further insight into the mode of action of hydroperoxides and certain reactive oxygen species that have been implicated in oxidative stress associated with various pathological conditions. The importance of the GSH/glutathione peroxidase system in metabolizing organic hydroperoxides is also demonstrated.
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PMID:Inhibition of the Ca pump of intact red blood cells by t-butyl hydroperoxide: importance of glutathione peroxidase. 824 Dec 52


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