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 objective of this study was to define the relationship between peroxyl radical-mediated cytotoxicity and lipid, protein and sulfhydryl oxidation using human erythrocytes as the target mammalian cell. We found that incubation of human erythrocytes with the peroxyl radical generator 2,2' azobis (2-amidinopropane) hydrochloride (AAPH) resulted in a time and dose-dependent increase in hemolysis such that at 50 mM AAPH maximum hemolysis was achieved at 120 min. Hemolysis was inhibited by hypoxia and by the addition of certain water soluble free radical scavengers such as 5-aminosalicylic acid (5-ASA), 4-ASA, N-acetyl-5-ASA and dimethyl thiourea. Peroxyl radical-mediated hemolysis did not appear to involve significant peroxidation of erythrocyte lipids nor did they enhance protein oxidation at times preceding hemolysis. Peroxyl radicals did however, significantly reduce by approximately 80% the intracellular levels of GSH and inhibit by approximately 90% erythrocyte Ca(2+)-Mg2+ ATPase activity at times preceding the hemolytic event. Our data as well as others suggest that extracellular oxidants promote the oxidation of intracellular compounds by interacting with certain redox active membrane components. Depletion of intracellular GSH stores using diamide did not result in hemolysis suggesting that oxidation of GSH alone does not promote hemolysis. Taken together, our data suggest that neither GSH oxidation, lipid peroxidation nor protein oxidation alone can account for peroxyl radical-mediated hemolysis. It remains to be determined whether free radical-mediated inactivation of Ca(2+)-Mg2+ ATPase is an important mechanism in this process.
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PMID:Peroxyl radical-mediated hemolysis: role of lipid, protein and sulfhydryl oxidation. 162 57

ESR spin trapping technique was used to detect and analyze free radical formation. When 6-hydroxydopamine (6-OHDA) was incubated alone or in the presence of a free radical generating system (H2O2 and FeSO4), hydroxyl free radicals were observed in a concentration-dependent manner. Glutathione was found to be the most effective scavenger of the ESR signal when compared with vitamin E or Mannitol. The addition of ethanol resulted in the formation of the pure hydroxyethyl free radicals. The amount of hydroxyethyl free radicals in the system was dependent upon the concentration of ethanol and the formation of hydroxyethyl free radicals correlated well with the extent of lipid peroxidation and the loss of enzymic activity of the membrane-bound (Na+,K+)-ATPase. We suggest that in the biological system ethanol may potentiate the neurotoxicity of 6-OHDA with the formation of hydroxyethyl free radicals, which are longer-lived and far more damaging to membranes than the hydroxyl radicals. These data lead us to further hypothesize that the neuronal degeneration caused by 6-OHDA and other compounds that generate free radicals could be potentiated in the presence of ethanol.
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PMID:The involvement of ethanol in the free radical reaction of 6-hydroxydopamine. 164 70

A substituted benzimidazole ([4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methylsulfinyl)- 1H-benzimidazole sodium salt (E3810), is a gastric proton pump (H+, K(+)-ATPase) inhibitor. E3810 and omeprazole inhibited acid accumulation dose dependently as measured with aminopyrine uptake in isolated rabbit gastric glands, their IC50 values being 0.16 and 0.36 microM, respectively. The addition of exogenous reduced glutathione (GSH) to the gland suspension reactivated dose dependently the acid secretion which had been inhibited by 2 microM E3810 or omeprazole as a function of the incubation time. Furthermore, GSH at 1 and 3 mM reversed the antisecretory effect of E3810 more quickly than it did that of omeprazole. The antisecretory effect of E3810 was slightly greater than that of omeprazole in histamine-stimulated fistula dogs in vivo. The duration of the antisecretory activity of E3810 at concentrations of 2 and 4 mg/kg was shorter than that of omeprazole at the same concentrations in pentagastrin-stimulated fistula dogs. The reversal of the antisecretory activity of the inhibitors in dogs is suggested to be due to the action of endogenous extracellular GSH, in addition to de novo synthesis of the proton pump, because bullfrog gastric mucosae were found in the present study to secrete GSH into the mucosal solution at the rate of about 0.25 nmol/min/g tissue.
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PMID:Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione. 165 Feb 10

The activities of Mg(2+)-dependent and Na(+)-K(+)-stimulated ATPase in homogenates of rat retina were measured in the presence of increasing concentrations of oxidized glutathione (GSSG). The Mg(2+)-ATPase was not inhibited by GSSG at any of the concentrations tested. The Na(+)-K(+)-stimulated ATPase was not inhibited by 1 mM GSSG, but its activity was decreased by 20 and 35%, respectively, in the presence of 5 and 10 mM GSSG. Other enzymatic measurements using supernatant fractions of rat retina showed that 1-10 mM GSSG did not inhibit the activities of hexokinase, glucose-6-phosphate dehydrogenase, or glyceraldehyde-3-phosphate dehydrogenase. These results suggest that GSSG is not likely to exert significant deleterious changes on cellular processes, at least in cells and tissues in which normal glutathione (GSH) concentration is 2 mM or lower.
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PMID:Effects of oxidized glutathione on ATPase activities in rat retina. 165 10

Lead (Pb) inhibited the activities of Na(+)-K+ ATPase (IC50 = 2.0 x 10(-6) M), K(+)-Para-Nitrophenyl phosphatase (PNPPase) (IC50 = 3.5 x 10(-6) M) and [3H]-ouabain binding (IC50 = 4.0 x 10(-5) M) in rat brain P2 fraction. A variable temperature or pH significantly elevated the inhibition of Na(+)-K+ ATPase by Pb in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation of Na(+)-K+ ATPase by ATP was indicated by a variation in Vmax values with no significant changes in Km values at any temperature studied. In the presence of Pb, for Na(+)-K+ ATPase at pH 6.5 and 8.5, Vmax was decreased with an increase in Km values suggesting a mixed type of inhibition. Sulfhydryl agents such as dithiothreitol (DTT) and cysteine (Cyst), but not glutathione (GSH) offered varied levels of protection against Pb-inhibition of Na(+)-K+ ATPase at pH 7.5 and 8.5. The present data suggest that inhibition of Na(+)-K+ ATPase by Pb is both temperature and pH-dependent. These results also indicate that Pb inhibited Na(+)-K+ ATPase by interfering with phosphorylation of enzyme molecule and dephosphorylation of the enzyme-phosphoryl complex and exerted an effect similar to that of SH-blocking agents.
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PMID:Effects of lead on pH and temperature-dependent substrate-activation kinetics of ATPase system and its protection by thiol compounds in rat brain. 166 9

Primary cultures of renal rabbit proximal tubule cells were initiated from a pure suspension of proximal tubule fragments. Proximal tubule cells were grown in a hormone-supplemented, serum-free medium containing low concentrations of antibiotics. Confluent monolayers exhibited multicellular dome formation, indicating the presence of transepithelial solute and water transport. Ultrastructural examination revealed a monolayer of polarized epithelial cells with tight junctions and sparse membraneous microvilli facing the culture medium. Time course biochemical characterization was performed using a palette of 12 enzymes, representative of important metabolic functions or pathways. Brush-border-associated enzymes (gamma-glutamyl transpeptidase and alanine aminopeptidase) were moderately reduced throughout the culture whereas alkaline phosphatase was markedly decreased at confluency. Mitochondrial and lysosomal marker enzymes were well preserved over the culture period. Glutathione-S-transferase activity remained stable during the 16-day culture period investigated. Glycolysis enzyme activities (lactate dehydrogenase and hexokinase) were enhanced, as a function of culture age. Na(+)-K(+)-ATPase activity rise was concomitant with the increase of glycolysis marker enzymes. In contrast, the gluconeogenesis marker enzyme, glucose-6-phosphatase, fell dramatically to reach a low level equivalent to 4% of the activity measured in isolated proximal tubules. Primary cultures exhibited several differentiated functions of the proximal tubule cell: (a) PTH alone was able to induce a significant stimulation of adenylate cyclase activity, unlike isoproterenol, thyrocalcitonin, and arginine vasopressin, and (b) sodium-dependent alpha-methylglucoside (AMG) transport was detected. This AMG uptake was selectively inhibited by phlorizin (5 X 10(-3) M), which is a competitive inhibitor of glucose uptake at the apical membrane. Complete characterization made it possible to investigate hitherto unexplored aspects of in vitro cultured proximal tubule cells. This primary culture model could provide a useful and reliable tool to investigate in vitro renal proximal tubule function, under normal conditions or after a drug-induced toxicity.
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PMID:Biochemical, functional, and morphological characterization of a primary culture of rabbit proximal tubule cells. 167

1. Organic xenobiotic metabolism often results in oxidative stress, involving GSH depletion, alteration of thiol/disulphide balance and peroxidation of membrane lipids. These events can lead to the disruption of Ca2+ homeostasis, through impairment of the Ca2+ translocases present in cellular membranes. Inhibition of the activity of Ca,Mg-ATPases due to oxidation of their SH groups would lead to uncontrolled rises in cytosolic Ca2+ levels resulting in loss of cell viability. 2. These observations seem to be of interest when interpreting the biochemical mechanisms of heavy metal cytotoxicity. Since these cations (such as Hg2+, Cu2+, Cd2+ and Zn2+) have an extremely high affinity for SH groups, they may affect the function of SH containing proteins, such as the Ca,Mg-ATPases, as in the case of oxidative stress. 3. Results are reported indicating that Hg2+ may stimulate Ca2+ influx through voltage-dependent channels in different experimental systems. Moreover, evidence is presented that heavy metals can inhibit Ca,Mg-ATPase activity and affect mitochondrial functions in the cells of different organisms. 4. The possibility that heavy metal cytotoxicity is mediated through disruption of Ca2+ homeostasis is discussed.
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PMID:Possible role of Ca2+ in heavy metal cytotoxicity. 167 78

These studies demonstrate that bilirubin-ditaurate (an analog of bilirubin-diglucuronide), lithocholic acid 3-O-sulfate, and lithocholic acid 3-O-glucuronide, which are believed to be transported from liver into bile through an active transport process stimulate ATP hydrolysis by purified dinitrophenylglutathione ATPase of human erythrocytes. The Km and Vmax values of the enzyme for these substrates are similar to those for dinitrophenylglutathione indicating the transport mechanisms for bilirubin conjugates, and anionic bile acid-conjugates from hepatocytes to bile and transport of GSH-conjugates from erythrocytes may be mediated by similar mechanisms.
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PMID:The anionic conjugates of bilirubin and bile acids stimulate ATP hydrolysis by S-(dinitrophenyl)glutathione ATPase of human erythrocyte. 182 61

Glyceraldehyde and other simple monosaccharides autoxidize under physiological conditions, forming dicarbonyl compounds and hydrogen peroxide via intermediate free radicals. These products may have deleterious effects on cell components. In this paper we study the effect of glyceraldehyde autoxidation on red-cell ATPase activities. The autoxidation of glyceraldehyde in imidazole-glycylglycine buffer, measured by oxygen consumption, depends on the buffer concentration and decreases in the presence of superoxide dismutase and catalase. The addition of DETAPAC inhibits the autoxidation almost completely. When human red-blood-cell membranes are incubated with glyceraldehyde, the red-blood-cell ATPase activities decrease significantly. The addition of DETAPAC, GSH and DTE (dithioerythritol) protects the enzyme from inactivation, but superoxide dismutase and catalase have no effect. Methylglyoxal (a dicarbonyl which is analogous to hydroxypyruvaldehyde derived from glyceraldehyde autoxidation) proved to have a powerful inhibitory action on ATPase activities. The addition of DTE completely protects the enzyme from inactivation, suggesting that the sulphydryl groups of the active site of the enzyme are the critical targets for dicarbonyl compounds.
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PMID:Oxidative inhibition of red blood cell ATPases by glyceraldehyde. 183 54

Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification.
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PMID:Glutathione and glutathione-related enzymes in busulfan treated rat lens. 191 43


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