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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify the damage site of complicated oxidative phosphorylation function after hemorrhagic shock in jaundiced liver mitochondria, the proton adenosine triphosphatase complex (H(+)-ATPase) activity of inside-out submitochondrial particles, mitochondrial membrane potential, and oxygen consumption in the presence of uncoupler were studied as indices of phosphorylation, membrane intactness, and oxidation, respectively. Hemorrhagic shock was induced according to the Wiggers' model (mean arterial blood pressure = 40 mm Hg) in rats made jaundiced by common bile duct ligation; rats that had undergone sham operations served as controls. After reinfusion of the shed blood, all of the control rats survived, but all of the jaundiced rats died. Liver mitochondria from jaundiced rats after 1 hour of hypotension demonstrated a 48% decrease in mitochondrial ATPase activity without remarkable changes in either oxidative activity or membrane potential of liver mitochondria. The reduction of ATPase activity appeared to be due to its release in the supernatants obtained from submitochondrial particles, because the ATPase activity of supernatants in jaundiced rats was significantly (p less than 0.001) higher than that of the controls. It is suggested that this enzyme plays a key role in energy restoration in recovery from shock.
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PMID:Alterations in the proton ATPase activity of rat liver mitochondria after hemorrhagic shock. 138 75

The effects of three tetrachlorobiphenylols [2',3',4',5'-tetrachloro-2-biphenylol (1); 2',3',4',5'-tetrachloro-4- biphenylol (2); and 2',3',4',5'-tetrachloro-3-biphenylol (3)]; three monochlorobiphenylols [5-chloro-2-biphenylol (5), 3-chloro-2-biphenylol (6); and 2-chloro-4-biphenylol (7)] and a tetrachlorobiphenyldiol [3,3',5,5'-tetrachloro-4,4'-biphenyldiol (4) on respiration, adenosine triphosphatase (ATPase) activity, and swelling in isolated mouse liver mitochondria have been investigated. Tetrachlorobiphenylols (1-3) and the tetrachlorobiphenyldiol (4) inhibited state-3 respiration in a concentration-dependent manner with succinate as substrate (flavin adenine dinucleotide [FAD]-linked) and the tetrachlorobiphenyldiol (4) caused a more pronounced inhibitory effect on state-3 respiration than the other congeners. The monochlorobiphenylols 5-7 were less active as inhibitors of state-3 mitochondrial respiration and significant effects were observed only at higher concentration (greater than or equal to 0.4 microM). However, in the presence of the nicotinamide adenine dinucleotide (NAD)-linked substrates (glutamate plus malate), hydroxylated PCBs (1-7) significantly inhibited mitochondrial state-3 respiration in a concentration-dependent manner. Compounds 5, 6, and 7 uncoupled mitochondrial oxidative phosphorylation only in the presence of FAD-linked substrate as evidenced by increased oxygen consumption during state-4 respiratory transition, stimulating ATPase activity, releasing oligomycin-inhibited respiration, and inducing mitochondrial swelling (5, 6, and 7). Tetrachlorobiphenylols 1, 2, and 3 had no effect on mitochondrial ATPase activity while the tetrachlorobiphenyldiol, 4, decreased the enzyme activity. The possible inhibitory site of electron transport by these compounds and their toxicologic significance is discussed.
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PMID:Effects of hydroxylated polychlorinated biphenyls on mouse liver mitochondrial oxidative phosphorylation. 183 67

The effect of the plant alkaloid ryanodine on the cardiac sarcoplasmic reticulum (SR) function, which plays a major role in the regulation of intracellular calcium and thereby in the generation of force, was studied by determining oxalate-supported calcium uptake, steady-state calcium load, calcium permeability, intravesicular-free calcium and Ca,Mg-adenosine triphosphatase (ATPase) activity of "heavy" vesicles in the presence or absence of the oxygen-free radical-generating system. In vitro generation of oxygen-free radicals by xanthine oxidase (0.09 u/ml), acting on xanthine (25 microM) as a substrate, increased the permeability of the vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased oxalate-supported calcium uptake and steady-state calcium load with no effect on Ca,Mg-ATPase activity. This effect of oxygen-free radicals was inhibited completely by superoxide dismutase, which eliminated completely superoxide anion radical production and caused an anticipated increase in hydrogen peroxide from the xanthine-xanthine oxidase reaction in our system. The xanthine-xanthine oxidase reaction decreased intravesicular-free calcium. The diminished level of intravesicular-free calcium, which was reflected by the decreased steady-state calcium load induced by oxygen-free radicals, was prevented by specific closure of the SR calcium release channel by ryanodine under established optimal conditions; under the same conditions, ryanodine also prevented superoxide dismutase-inhibitable reduction of calcium uptake induced by oxygen-free radicals in the presence or absence of oxalate. Ryanodine was without effect on Ca,Mg-ATPase activity by itself and had no effect on any of the changes in calcium permeability mediated by the generation of oxygen-free radicals under the experimental conditions used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ryanodine on oxygen free radical-induced dysfunction of cardiac sarcoplasmic reticulum. 184 30

Prostacyclin (PGI2) did not alter the basal perfusion pressure in the isolated rat mesenteric arteries perfused with Krebs' solution, but produced a biphasic effect in arteries preconstricted with norepinephrine or arginine vasopressin: constriction, then prolonged dilation. Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM). The present study elucidates the mechanism of these PGI2 actions. Indomethacin (0.28 microM) SQ 29548 (1 microM, thromboxane A2 receptor antagonist), saralasin (1 microM, angiotensin II receptor antagonist) or the free radical scavengers, superoxide dismutase (60 U/ml) and catalase (40 U/ml) did not inhibit the initial vasoconstriction, suggesting it was not mediated through endothelially generated thromboxane A2, angiotensin II or oxygen-derived free radicals. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (50 microM; Ca++ chelating agent), 8-(diethyl-amino)octyl 3,4,5-trimethoxy benzoate (10 microM; intracellular Ca++ antagonist), or neomycin (5 mM; phospholipase-C inhibitor) abolished the vasoconstriction. Ouabain (0.5 mM) did not affect the vasodilation, but perfusion with excess (50 mM) or 0 K+ Krebs' solution abolished it, suggesting this PGI2 action involves changes in membrane K+ conductance via a mechanism independent of Na+/K+ adenosine triphosphatase. Vasodilation evoked by BRL 34915 (K+ channel activator) was similarly attenuated under these conditions, but not by ouabain. Furthermore, procaine (1 mM; nonspecific K+ channel inhibitor), but not apamin (0.5 microM) or tetraethylammonium (10 mM) blocked PGI2- and BRL 34915-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries. 210 93

1. The kidney taken from a rat rendered nephrotic by exposure to puromycin aminonucleoside retains sodium abnormally when perfused in isolation and has an abnormally low vascular resistance (J. D. Firth et al., Clin. Sci. 1989; 76, 387-95). In this study the relation of oxygen consumption to sodium reabsorption has been examined in the isolated nephrotic organ, which has also been exposed to a variety of natriuretic agents and to the effect of inhibition of metabolism by cooling, in an attempt to discern the transport process, or processes, responsible for abnormal tubular handling of sodium. In addition, the effects of three endogenous vasoconstrictors, noradrenaline, angiotensin II and endothelin, on the function of the isolated nephrotic kidney have been examined. 2. The ratio of mol of sodium reabsorbed by the tubules of the isolated nephrotic kidney to mol of oxygen consumed was reduced in comparison with the control kidney (means +/- SEM): 9.22 +/- 0.97 versus 15.43 +/- 1.55 (P less than 0.002). 3. In the presence of ouabain (1 mmol/l), acetazolamide (1 mmol/l), frusemide (200 mumol/l), the combination of these three agents together, hydroflumethiazide (100 mumol/l), benzamil (100 nmol/l) or atrial natriuretic peptide (1000 pmol/l), a lesser increment in sodium excretion was induced in the isolated nephrotic kidney than in the control kidney and the nephrotic organ continued to excrete less sodium in both absolute and fractional terms. 4. This suggests that enhanced tubular sodium reabsorption in the isolated nephrotic kidney does not depend upon abnormally increased activity of the Na+/K(+)-adenosine triphosphatase, bicarbonate-dependent sodium transport, Na+/K+/2Cl- co-transport, electrically neutral proportionate reabsorption of sodium and chloride (distal tubule), epithelial sodium channel (distal tubule) or atrial natriuretic peptide-sensitive sodium transport processes. 5. When isolated nephrotic kidneys and normal kidneys were cooled to 8-10 degrees C the handling of sodium became virtually identical in the two groups. On re-warming to 37 degrees C, the original differences in sodium handling between nephrotic and control kidneys were restored. This implies that the mechanism responsible for the abnormal tendency to retain sodium is temperature-sensitive; as yet it remains otherwise undefined. 6. The sensitivity of the renal vessels to noradrenaline, angiotension II and endothelin, as judged by the percentage reduction in perfusate flow rate produced by a given concentration of any of these agents, was not substantially altered in the nephrotic kidney compared with the control kidney. Increase in vascular tone was not associated with amelioration of the tendency of the isolated nephrotic organ to retain sodium. Increasing concentrations of angiotensin II caused the filtration rate to increase in the nephrotic kidney. This effect was unexpected: in the control preparation, as anticipated, angiotensin II caused the filtration rate to decrease.
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PMID:Effect of natriuretic agents, vasoactive agents and of the inhibition of metabolism on sodium handling in the isolated perfused kidney of the nephrotic rat. 217 43

Isolated adult rat hearts perfused in an isovolumic mode were used to study the effects of sodium-potassium pump inhibition and sodium-calcium exchange alterations on the tissue content of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH, all measured by phosphorus-31 nuclear magnetic resonance spectroscopy. Rates of oxygen consumption, contractile function, and the cell contents of calcium, sodium, and potassium also were determined. The inhibition of sodium-potassium adenosine triphosphatase, either by the reduction in perfusate potassium from 5.9 to 1 millimolar or less, or by the addition of 10(-4) molar ouabain, transiently increased systolic pressure. This was followed by a decrease in systolic pressure, an increase in diastolic pressure, and eventual inexcitability. This contractile profile was accompanied by a persistent increase in oxygen consumption, a monotonic decline in cellular adenosine triphosphate and phosphocreatine content, the development of marked intracellular acidosis, a gain in cell sodium and calcium content, and a reduction in cell potassium. Quite similar metabolic changes were also observed when cell calcium was increased after a reduction in perfusate sodium. These metabolic and contractile effects could be prevented or reversed by decreasing perfusate calcium. The results emphasize the profound role of calcium in modulating cell oxygen consumption, energy balance, pH, excitability, and force production. These data are discussed in light of changes in the myocardial energy supply/demand balance, as well as from the viewpoint of the known competition between mechanisms for mitochondrial calcium transport vs. high-energy phosphate production.
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PMID:A phosphorus-31 nuclear magnetic resonance study of the metabolic, contractile, and ionic consequences of induced calcium alterations in the isovolumic rat heart. 242 40

The generation of free oxygen radicals from the xanthine-xanthine oxidase system produced a decrease in the steady-state calcium load of canine cardiac sarcoplasmic reticulum (SR) vesicles and an increase in the SR passive calcium permeability. This effect of free oxygen radicals was completely inhibited by superoxide dismutase, a scavenger of superoxide anion radical (.O2-). Treatment of intact SR with a specific calmodulin antagonist, compound 48/80 or W-7, lead to the enhancement of the free oxygen radical-mediated reduction of steady-state calcium accumulation with little effect on passive calcium permeability and Ca,Mg-adenosine triphosphatase activity. The effects of free oxygen radicals and the calmodulin antagonists on steady-state calcium accumulation, but not on passive calcium permeability, were only observed in the presence of the endogenous calmodulin of SR vesicles. These results indicate that stimulation by .O2- and/or a closely related species of free oxygen radical of the passive calcium leak pathway is not calmodulin-dependent and is not a potent way of changing the steady-state calcium accumulation. Hence, we propose that calmodulin-dependent component of calcium fluxes in cardiac SR vesicles is modified directly by free oxygen radicals, and that free oxygen radicals can reduce steady-state calcium accumulation due to increased calcium release through a calcium efflux pathway which is inhibited by calmodulin, but not due to reduced catalytic activity of the pump.
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PMID:Calmodulin and free oxygen radicals interaction with steady-state calcium accumulation and passive calcium permeability of cardiac sarcoplasmic reticulum. 252 16

New light microscopic visualization methods were developed for the histochemical detection of non-specific alkaline and acid phosphatase, Mg-, Ca- and Na, K-dependent adenosine triphosphatase, myosin adenosine triphosphatase, glucose-6-phosphatase, 5'-nucleotidase and thiamine pyrophosphatase with cerium ions as trapping agents in cryostat and plastic sections. The techniques are based on the conversion of cerium phosphate into cerium perhydroxide by H2O2 which decomposes at 55 degrees-60 degrees C into cerium hydroxide and oxygen radicals. These radicals are able to oxidize diaminobenzidine (DAB) to DAB brown. Addition of nickel ions to the DAB-H2O2 mixture generates bluish-black stained nickel-DAB complexes. Compared with the classical metal precipitation, azo, azoindoxyl and tetrazolium procedures the H2O2-DAB and especially the H2O2-DAB-nickel methods provided identical or superior results in catalytic phosphatase histochemistry and immunohistochemistry when using non-specific alkaline phosphatase as the enzyme label.
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PMID:The cerium perhydroxide-diaminobenzidine (Ce-H2O2-DAB) procedure. New methods for light microscopic phosphatase histochemistry and immunohistochemistry. 285 63

A mutant strain of Escherichia coli was isolated in which Gly-48 of the mature epsilon-subunit of the energy-transducing adenosine triphosphatase was replaced by Asp. This amino acid substitution caused inhibition of ATPase activity (about 70%), loss of ATP-dependent proton translocation and lowered oxidative phosphorylation, but did not affect proton translocation through the F0. Purified F1-ATPase from the mutant strain bound to stripped membranes with the same affinity as the normal F1-ATPase. Partial revertant strains were isolated in which Pro-47 of the epsilon-subunit was replaced by Ser or Thr. Pro-47 and Gly-48 are predicted to be residues 2 and 3 in a Type II beta-turn and the Gly-48 to Asp substitution is predicted to cause a change from a Type II to a Type I or III beta-turn. Space-filling models of the beta-turn (residues 46-49) in the normal, mutant and partial revertant epsilon-subunits indicate that the peptide oxygen between Pro-47 and Gly-48 is in a different position to the peptide oxygen between Pro-47 and Asp-48 and that the substitution of Pro-47 by either Ser or Thr restores an oxygen close to the original position. It is suggested that the peptide oxygen between Pro-47 and Gly-48 of the epsilon-subunit is involved either structurally in inter-subunit H-bonding or directly in proton movements through the F1-ATPase.
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PMID:Amino acid substitutions in the epsilon-subunit of the F1F0-ATPase of Escherichia coli. 287 66

We have examined intermediate Pi-water oxygen exchange during [gamma-18O]ATP hydrolysis by the F1 adenosine triphosphatase from Escherichia coli K-12. Water oxygen incorporation into each Pi released was increased as ATP concentration was lowered as observed previously for the same reaction catalyzed by the enzyme from eukaryotic sources. Heterogeneous distributions of 18O in product Pi were produced by coexisting epsilon subunit-replete and epsilon subunit-depleted enzyme molecules. The epsilon-replete enzyme showed a much higher probability for oxygen exchange. These data imply that the epsilon subunit inhibits net ATP hydrolysis by imposing conformational constraints which reduce the cooperative conformational interactions that promote ADP and Pi release. Four enzyme variants altered in alpha or beta subunit structure with reduced net hydrolytic activity showed sharply increased oxygen exchange during ATP hydrolysis. Heterogeneity was apparent in the 18O distribution of the product Pi, however. That behavior could reflect hindered conformational interactions and/or increased affinity of the alpha 3 beta 3 gamma delta complex for the epsilon subunit. In contrast, enzyme from mutant uncA401 showed very little oxygen exchange accompanying hydrolysis of 20 microM ATP. This is the only enzyme so far reported with this unusual property. Its rate limitation appears to be in the hydrolytic rather than the product release step of the catalytic sequence.
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PMID:Catalytic properties of the F1-adenosine triphosphatase from Escherichia coli K-12 and its genetic variants as revealed by 18O exchanges. 288 Aug 43


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