Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of short- or long-term complete cerebral ischemia were studied in the gerbil brain using a multi-parameter monitoring system. Metabolic (NADH redox state) and hemodynamic responses were monitored by surface fluorometry-reflectometry. Ionic activities (K+ and pH) were measured by surface macroelectrodes. Electrical activity was evaluated by monitoring the general electrocorticogram (ECoG) as well as local DC steady potential (two sites). Two groups of gerbils were studied to compare the effects of 4-5 min occlusions with those of 30 min complete ischemia. During bilateral carotid artery occlusion the cortex is exposed to complete ischemia resulting in the complete depletion of O2 with attendant maximal reduction of NADH. Extracellular K+ began to increase as soon as energy reserves were decreased with a time course suggesting two different kinetic areas. Surface pH decreased very shortly after the occlusion. During the recovery phase, NADH was reoxidized soon after recirculation, whereas the pH and K+ recovery showed a short delay. ECoG did not recover even when all other parameters reached base-line levels. The recovery of all the measured parameters was correlated to the duration of the ischemic insult; i.e., the recovery from 30 min of ischemia took significantly longer than after 5 min of ischemia. We conclude that pH recovery depends on recirculation and adequate O2 supply to the tissue, whereas K+ recovery required not only an adequate O2 supply but also the integrity of the adenosine triphosphatase system.
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PMID:Metabolic, ionic, and electrical responses of gerbil brain to ischemia. 397 Jan 91

Glucose, insulin, potassium (GIK: 300 g glucose + 50 U insulin + 80 mEq KC1/L) was administered to anesthetized dogs as a 30-ml bolus followed by 1.5 ml/kg/h for 2 h. Five populations were studied: control (C, n = 6); 60 min hypothermic arrest both without (I, n = 6) and with pretreatment (I + GIK, n = 6); 60 min hypothermic arrest followed by reperfusion without (R, n = 6) and with pretreatment (R + GIK, n = 6). Glycogen content declined during the ischemic and reperfusion periods whether or not GIK pretreatment was utilized. Glycogen values did not differ significantly among the four groups. GIK pretreatment significantly protected sarcoplasmic reticulum (SR) calcium uptake rates. SR Ca2+ + Mg2+ adenosine triphosphatase (ATPase) activity was unaffected in the I group, depressed in the R group, but protected by GIK pretreatment. Myofibrillar pCa-ATPase activity was significantly depressed in the I group and unaffected by GIK pretreatment. In the R + GIK group, myofibrillar pCa-ATPase activity was identical to controls at all calcium concentrations except for Vmax. In vitro, generation of the superoxide anion by a xanthine-xanthine oxidase system at pH 7.0 significantly depressed both SR calcium uptake and ATPase activity, and this depression was partially reversible by glucose. Generation of the hydroxyl free radical and pH 6.4 significantly depressed calcium uptake but not ATPase activity, and this depression was reversible with glucose + superoxide dismutase. GIK pretreatment exerts a protective effect on the excitation-contraction coupling system during hypothermic global ischemia and reperfusion. Glycogen augmentation after short-term GIK infusion was not significantly different. It is hypothesized that an additional mechanism by which GIK may protect subcellular function is by serving as a scavenger of free radicals generated during the ischemic/reperfusion process.
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PMID:Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: a new proposed mechanism by the scavenging of free radicals. 618 57

Previous studies have identified a cellular energy deficit in gastric mucosa after ischemia. We studied the processes of energy generation (mitochondrial function) and energy utilization (microsomal adenosine triphosphatase [ATPase] activity) in an experimental model of stress. Rabbits were divided into four groups: I, fed controls (n = 7); II, 24-hour fasted controls (n = 7); III, fasted, anesthetized, and cannulated controls (n = 7); and IV, fasted, anesthetized, cannulated, and bled rabbits. Bleeding consisted of 25 ml blood/kg into a reservoir for 60 minutes; the blood was then reinfused. Animals were killed 30 minutes after reinfusion; antral, corpus, and fundus mucosae were dissected; each region of mucosa was homogenized; and mitochondrial and microsomal fractions were isolated by differential centrifugation. No animals in group I or II had gastric ulcerations. Three of seven animals in group III and all group IV animals had corpus and fundus ulcers. No antral ulcers were seen in any group. The respiratory control index (RCI) of antral mitochondria was increased in groups II, III, and IV but was unchanged in all groups of corpus and fundus mitochondria. Studies of microsomal ATPase activity indicated increased activity of potassium-stimulated ATPase in the corpus mucosa. In the corpus mucosa, total ATPase activity was increased primarily as a consequence of increased potassium-stimulated ATPase. These data indicate that increased RCI is associated with gastric mucosal integrity in the antrum. Accelerated utilization of available adenosine triphosphate by corpus membrane ATPases may further compromise energy homeostasis during stress.
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PMID:Bioenergy metabolism of gastric mucosa during stress. 621 53

Digitalis sensitivity of the heart is increased in patients with ischemic heart disease. Whether this elevation of digitalis sensitivity occurs as the result of ischemia-induced changes in the cardiac tissue and whether changes in the sarcolemmal Na,K-adenosine triphosphatase (ATPase) or reserve capacity of the sodium pump are responsible for the increased digitalis sensitivity were examined using isolated heart preparations obtained from guinea pigs. Ligation of the left anterior descending coronary artery (LAD) in Langendorff preparations 40 min before perfusion with a toxic concentration (either 1.8 or 2.5 microM) of digoxin decreased the time to the onset of arrhythmias. LAD-ligation by itself did not cause arrhythmias. The time to the onset of arrhythmias during digoxin perfusion was slightly longer in preparations obtained from reserpine-treated animals; however, the reserpine pretreatment failed to alter the effect of LAD ligation on digitalis sensitivity, indicating that the release of catecholamines is not involved in the sensitization. The effects of ischemia on Na,K-ATPase and sodium pump activities, glycoside binding to the enzyme and reserve capacity of the sodium pump were examined in globally ischemic Langendorff preparations. The preparations were perfused with a Krebs-Henseleit bicarbonate buffer solution (pH 7.4) saturated with a 95% O2-5% CO2 gas mixture at a control flow rate of 2.5 ml/g of tissue per min or at 5 or 0% of the control flow rate. After 6 hr of zero perfusion, Na,K-ATPase activity and the number of specific ouabain binding sites were reduced in ventricular muscle homogenates. However, the remaining Na,K-ATPase was not altered in its sensitivity to dihydrodigoxin-induced inhibition or affinity of binding sites for ouabain, sodium or potassium. Similar results were observed after reperfusion following 2 or 5 hr of zero perfusion. A 5% perfusion for 2 or 6 hr, or zero perfusion for 2 hr failed to affect Na,K-ATPase activity in muscle homogenates. Sodium pump activity in ventricular slices, estimated from the ouabain-sensitive 86Rb+ uptake, was unchanged after 5% perfusion or zero perfusion for 2 hr, but was significantly reduced after a 20-min reperfusion following 2 hr of zero perfusion. Reserve capacity of the sodium pump, as estimated from the differences in 42K+ uptake by right ventricular strips under 1.5 and 7 Hz stimulation, was unaffected by 2 hr of 5% perfusion. These results indicate that coronary artery occlusion enhances the arrhythmogenic action of digitalis in isolated heart preparations. This change in digitalis sensitivity produced by 40 min of occlusion cannot be explained by reductions in Na,K-ATPase activity or sodium pump reserve capacity as 2 hr of zero perfusion does not alter Na,K-ATPase or sodium pump activity in ventricular tissue.
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PMID:Ischemia-induced enhancement of digitalis sensitivity in isolated guinea-pig heart. 630 6

Acute myocardial ischemia reduces tolerance of the heart to arrhythmogenic actions of digitalis glycosides. Because both ischemia and the glycoside produce profound changes in activity of the autonomic nervous system and because sympathetic discharge or catecholamines enhance toxic actions of the cardiac glycosides, the possibility that alterations in digitalis sensitivity of ischemic heart involve changes in sympathetic nerve activity was examined using alpha-chloralose-anesthetized cats. Left anterior descending coronary artery (LAD) was completely occluded by ligation and, 40 min later, a slow i.v. infusion of digoxin was started at a rate of 1 microgram/kg/min. LAD ligation alone did not produce arrhythmias in that condition, but shortened the time to onset of digoxin-induced arrhythmias and thereby reduced the amount of digoxin required to produce the toxic manifestation. Concomitantly, digoxin concentration in plasma and nonischemic areas of the heart were lower in LAD-ligated cats at the onset of arrhythmias than those in sham-operated cats. Myocardial digoxin content in the ischemic area of the LAD-occluded heart was lower than that in nonischemic areas of the same heart. At the onset of digoxin-induced arrhythmias, Na,K-adenosine triphosphatase activity of ischemic myocardium was significantly higher than that in the nonischemic area, reflecting a lower digoxin occupancy of the glycoside binding sites on the sodium pump. Spinal cord (C1) transection or propranolol treatment prolonged the time to arrhythmias in both control and LAD-ligated cats, but failed to abolish the effect of LAD ligation to augment digoxin toxicity. Bilateral vagotomy also did not alter the enhancement of digoxin toxicity caused by ligation of LAD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of sympathetic nervous system in ischemia-induced reduction of digoxin tolerance in anesthetized cats. 632 71

Recent experimental work implicates oxygen free radicals as mediators of ischemia/reperfusion injury. A simple cardioplegic solution was designed to scavenge superoxide anion and hydroxyl free radical with superoxide dismutase (10 micrograms/ml), mannitol (325 mOsm/L), and KCl 25 mEq/L (FRS). Hemodynamic and subcellular functions were studied in seven in situ canine models of hypothermic global ischemia receiving FRS, compared to a group (n = 7) receiving hyperosmolar, hyperkalemic saline (HSK) and to a standard model of topical hypothermia (TH, n = 5). Following 60 minutes of ischemia (10 degrees to 15 degrees C), hearts were reperfused and rewarmed. After 45 minutes of reperfusion, left ventricular peak systolic pressure (LVPSP), developed pressure (LVDP), dP/dt max, -dP/dt max, compliance, and elastic stiffness constant (K) were improved in the FRS group and not significantly different from control. Sarcoplasmic reticulum (SR) calcium transport in the FRS group was significantly improved (control = 1.077 +/- 0.022, TH = 0.754 +/- 0.018, HSK = 0.725 +/- 0.05, and FRS = 0.966 +/- 0.05 mumol/mg-min). Calcium adenosine triphosphatase (ATPase) activity did not differ significantly from control at pH 7.0. In this model of hypothermic global ischemia and reperfusion, free radical scavengers provide significant protection of mechanical and subcellular function. These findings support the hypothesis that oxygen free radicals are important mediators of myocardial ischemia and reperfusion injury.
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PMID:Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers. 687 62

Progressive cell injury occurs with shock and ischemia, beginning with functional changes in the cell and cell membrane. Membrane transport and potential decrease, Na+ enters and K+ leaves cells; N+-K+ adenosine triphosphatase is activated, adenosine triphosphate (ATP) is used, and mitochondria are stimulated as increased lactate produces acidosis. Energy and cyclic adenosine monophosphate levels decrease, Ca2+ regulation is compromised, and nuclear function and protein synthesis are depressed. The cell swells, and further membrane changes occur with altered hormonal effects and mitochondrial uncoupling. Finally, lysosomes leak, intracellular and mitochondria disruption occurs, and the cell is destroyed. Based on these changes, attempts were made to directly support cell function during low-flow states. After volume replacement and vasoactive agents, other modalities, eg, substrates, membrane-stabilizing solutions, osmotic agents, and energy compounds were used. The use of ATP-MgCl2 was helpful in many experimental low-flow states, with an improvement in cell function mediated by micro-circulatory, cell membrane, or energy-recycling effects. Clinical examples of altered cell and organ function with ischemia and shock are numerous and play a critical role in the development of multiple systems failure. The potential for biochemical support and correction of these problems is now recognized. Benefits have already been achieved in myocardial preservation during cardiac operations, kidney preservation for transplantation, and circulatory and metabolic support of the injured and septic patient.
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PMID:Alterations in cell function with ischemia and shock and their correction. 702

Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad-spectrum mitogenic and non-mitogenic activities of FGFs inspired us to study its protecting effects on tissue injuries in ischemia reperfusion condition. We found that systemic administration of aFGF after reperfusion onset prevented severe skeletal muscle injuries. In rats treated with aFGF, the tissue edema was reduced significantly, the tissue viability was increased, and the muscle fibers contained more succinate dehydrogenase (SDH) and adenosine triphosphatase (ATPase). The pathological results supported the concept of improved prevention with aFGF treatment. The possible tissue protection by aFGF may come from its ability to regulate the concentration of extra- and intracellular calcium ion. Besides, it may moderate other Ca2+ dependent enzyme conversion processes. Also, it may take part in the vascular tone regulation under ischemia and reperfusion conditions. These results suggest further study of tissue ischemia prevention with FGF and its possible mechanisms in the future.
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PMID:Acidic fibroblast growth factor reduces rat skeletal muscle damage caused by ischemia and reperfusion. 754 Sep 68

The effects of phenytoin, carbamazepine and valproic acid on alterations in sodium-potassium-adenosine triphosphatase activity during ischemia were studied in the rat brain. Pretreatment with phenytoin and carbamazepine prevented a reduction of this activity, which, without either treatment, was observed in the cerebral hemisphere exposed to 30-minute ischemia resulting from unilateral middle cerebral artery occlusion. Valproic acid, on the other hand, did not principally affect the ischemic impairment of this membrane-bound enzyme activity. These results lend support to the previously proposed use of phenytoin in cerebral ischemia, but also suggest the therapeutic availability of another common anticonvulsant, carbamazepine, for treatment of the insult.
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PMID:Effects of the conventional anticonvulsants, phenytoin, carbamazepine, and valproic acid, on sodium-potassium-adenosine triphosphatase in acute ischemic brain. 808 89

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracellular Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca(2+)-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca(2+)-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca(2+)-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequenstration and plasma membrane Ca(2+)-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.
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PMID:Calcium movement in ischemia-tolerant hippocampal CA1 neurons after transient forebrain ischemia in gerbils. 878 35


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