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)

Major mitochondrial phospholipids were examined in rat brain after 30 minutes of reperfusion following 30- or 60-minute periods of ischemia to examine their changes and explore their relationship to mitochondrial dysfunction during postischemic reperfusion. The amount of phospholipids and the percentage of polyunsaturated fatty acid chains, which tended to decrease during 30 minutes of ischemia, recovered after reperfusion. However, after ischemia lasting for 60 minutes, these parameters did not recover but decreased further, suggesting progressive disruption of phospholipids by phospholipase A2 after reperfusion. These changes were particularly notable in cardiolipin, which is contained specifically in mitochondria. The changes were also closely associated with mitochondrial respiration and respiratory enzyme (cytochrome c oxidase and F0F1-adenosine triphosphatase) activities, which have been known to correlate with the amount of cardiolipin. These results suggest that phospholipid metabolism in mitochondrial membranes is an important factor bearing on the integrity of energy metabolism during postischemic reperfusion.
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PMID:Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain. 130 64

Peroxidative stress, exerted by oxygen free radicals, seems to be an important mechanism of the ischemia-reperfusion myocardial damage. In the present study we evaluated the modifications of sarcoplasmic reticulum function subjected to peroxidation by ferric ions. A subcellular fraction enriched in sarcoplasmic reticulum was obtained from rabbit hearts by homogenization and differential centrifugations. Sarcoplasmic reticulum vesicles were peroxidated through incubation for 5 min at 37 degrees C in presence of ferric cloride (FeCl3) ranging in concentration between 0.3 and 0.9 mM. Peroxidation of sarcoplasmic reticulum vesicles determined a dose-dependent reduction of Ca-uptake (39.2 +/- 10.3, 36.5 +/- 9.9, 28.9 +/- 8.4 and 18.8 +/- 8.2 nmol/min/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; NS, p less than 0.05 and less than 0.01, respectively) which was paralleled by an increase in the production of malondialdehyde, an index of lipid peroxidation (1.0 +/- 1.0, 7.0 +/- 3.2, 14.1 +/- 3.9 and 27.0 +/- 4.7 nmol/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; p less than 0.05, less than 0.01 and less than 0.01, respectively). Depression of Ca-uptake was not accounted for by modifications of Ca-ATPase activity or membrane aspecific permeability to Ca++ ions, since these parameters were not affected by exposure to 0.3-0.9 mM FeCl3. On the contrary, the responsiveness of Ca-release channels to the specific inhibitor ryanodine was greatly altered, even at lower FeCl3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of oxygen free radicals on the function of the cardiac sarcoplasmic reticulum]. 132 20

Severity of renal injury and recovery of function in acute renal failure (ARF) are strongly related not only to the magnitude and nature of ARF insult but also to numerous factors in the host which govern renal susceptibility to the insult and repair of renal lesion. Prior ARF affords resistance to a rechallenge with the same or different ARF insult. The mechanisms for this acquired resistance to ARF have not been well established, but suggested mechanisms include (a) increased resistance of regenerated tubular epithelial cells to a rechallenge, (b) glomerular refractoriness to vasoactive substances, (c) failure of damaged kidney to concentrate the toxic substance, (d) enhanced antioxidant enzyme activity in glomeruli, and (e) increased Na(+)-K(+)-ATPase activity in regenerated tubular epithelial cells. Controversy still exists regarding roles of these factors in the resistance to renal failure. Functional and morphologic recovery of postischemic kidney is enhanced by antecedent unilateral nephrectomy but delayed in the presence of the contralateral kidney. The mechanisms for the effect of uninephrectomy remain unsettled. Recent studies suggest contributions of changes in preglomerular vascular resistance; alterations in the environment which follow ischemia to all functioning excretory renal tissues; and altered production and release of vasoactive substances such as angiotensin, endothelin, thromboxane, and atrial natriuretic peptide.
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PMID:Factors affecting severity of renal injury and recovery of function in acute renal failure. 132 11

Alterations in cellular membrane structure and the subsequent failure of its function after CNS ischemia were monitored by analyzing changes in the plasma membrane marker enzyme (Na(+) + K(+)-ATPase. The levels of two isozymes of (Na(+) + K(+)-ATPase, alpha+ and alpha, which have distinct cellular and anatomical distributions, were studied to determine if differential cellular damage occurs in primary and peri-ischemic injury areas. The efficacy of monosialoganglioside (GM1) treatment was assessed, since this glycosphingolipid has been shown to reduce ischemic injury by protecting cell membrane structure/function. Using a rat model of cortical focal ischemia, levels of both ATPase isozyme activities were assayed in total membrane fractions from primary ischemic tissue (parietal cortex) and three peri-ischemic tissue areas (frontal, occipital, and temporal cortex) at 1, 3, 5, 7, and 14 days after ischemia. No significant loss of either isozyme's activity occurred in any tissue area at 1 day after ischemia. At 5 days, in the primary ischemic area, both isozyme activity levels decreased by 70-75%. The alpha+ enzyme activity loss persisted up to 14 days, while a 17% recovery in alpha activity occurred. In the three peri-ischemic tissue areas, enzyme activity losses ranged from 42%-59% at 3 days after ischemia. A complete restoration of both isozyme activities was seen at 14 days. After three days of GM1 ganglioside treatment there was no loss of total (Na*+) + K(+)-ATPase activity in the three peri-ischemic areas, and a significantly reduced loss in the primary infarct tissue. An autoradiographic analysis of brain coronal sections using 3H-ouabain supports the enzymatic data and GM1 effects. Reductions in 3H-ouabain binding in all cortical layers at 3 days after ischemia were visualized. GM1 treatment significantly reduced these 3H-ouabain binding losses. In summary, time-dependent quantitative changes in activity levels of ATPase isozymes (alpha+ and alpha) reflect the different degree of membrane damage that occurs in primary vs. peri-ischemic tissues (e.g., irreversible vs. reversible membrane damage), and that ischemia affects cell membranes of all neural elements in a largely similar fashion. GM1 ganglioside was found to reduce plasma membrane damage in all CNS cell types.
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PMID:Loss and recovery of activities of alpha+ and alpha isozymes of (Na(+) + K+)-ATPase in cortical focal ischemia: GM1 ganglioside protects plasma membrane structure and function. 132 61

The polar distribution of Na(+)-K(+)-ATPase to the basolateral membrane of proximal tubule cells is essential for the efficient and vectorial reabsorption of Na+ and may be dependent on the formation of a metabolically stable, detergent-insoluble complex of Na(+)-K(+)-ATPase with the actin membrane cytoskeleton. The present studies utilized immunocytochemical techniques to demonstrate and quantify the apical redistribution of Na(+)-K(+)-ATPase during mild ischemia (15 min) that occurred in proximal (1.3 +/- 0.9 vs. 4.5 +/- 1.1 particles/100 microns surface membrane, P less than 0.01) but not distal tubule cells. Treatment of control apical membranes with 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C), a fluidizing agent, markedly increased membrane fluidity without any effect on Na(+)-K(+)-ATPase activity. In brush-border membrane vesicles isolated after ischemia, however, A2C further increased an already elevated Na(+)-K(+)-ATPase activity. During ischemia, total cellular Na(+)-K(+)-ATPase activity remained unaltered, but the Triton X-100-soluble (noncytoskeleton associated) fraction of Na(+)-K(+)-ATPase increased significantly following 15 and 30 min. There was a corresponding decrease in the Triton X-100-insoluble fraction of Na(+)-K(+)-ATPase, with the ratio of detergent-soluble to -insoluble Na(+)-K(+)-ATPase increasing from 13 +/- 2 to 32 +/- 5% (P less than 0.01) during 30 min of ischemia. Western blot analysis of the Triton X-100-soluble fraction, following 30 min of ischemic injury, revealed the presence of Na(+)-K(+)-ATPase, actin, fodrin, and uvomorulin. However, in a fraction highly enriched for Na(+)-K(+)-ATPase, neither actin, fodrin, nor uvomorulin was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)-K(+)-ATPase during ischemia. 132 35

High potassium solution is one of the most commonly used cardioplegic solution, but the mechanism of action is still poorly defined. In the present study, isolated rat hearts were utilized to investigate the protective effects and mechanism of action of high potassium against ischemia/reperfusion injury. The results showed that high potassium (22 mmol/L) apparently improved the recovery of contraction amplitude (P < 0.01), inhibited the rise of resting tension (P < 0.01) and abolished ventricular fibrillation during reperfusion after global ischemia for 40 minutes. Moreover, high potassium could preserve myocardial Na+, K(+)-ATPase activity (P < 0.01) and inhibit sodium and calcium overload (P < 0.01) during reperfusion. The results indicate that small amount of high potassium solution (5 ml) administered even after ischemic arrest of rat heart has remarkable protective effects against ischemia/reperfusion injury at 37 degrees C. Its mechanism of action is at least partially by preserving Na+,K(+)-ATPase activity and inhibiting sodium and calcium overload.
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PMID:[Protective effects of high potassium administered after ischemic arrest against reperfusion injury in isolated rat hearts]. 133 40

Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were significantly injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na,K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. Results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to: 1) preserved myocardial Na,K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and 2) reduction of oxygen free radical generation during reperfusion.
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PMID:Mechanisms of protective effects of berbamine on ischemia/reperfusion injury in isolated rat heart. 133 20

We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.
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PMID:Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. 133 23

Bepridil is an antianginal agent with multiple therapeutic actions. It decreases calcium influx through potential-dependent and receptor-operated sarcolemmic calcium channels and acts intracellularly as a calmodulin antagonist and calcium sensitizer. Thus, in cardiac muscle it enhances the sensitivity of troponin C to calcium, stimulates myofibrillar adenosine triphosphatase activity, removes calmodulin's inhibitory effect on sarcoplasmic reticulum calcium release, and inhibits sodium-calcium exchange--actions that tend to offset the effects of calcium influx blockade on cardiac contractile force. However, in vascular smooth muscle where the calcium-calmodulin complex promotes muscle contraction by activating myosin light-chain kinase phosphorylation of contractile proteins, calmodulin antagonism, coupled with bepridil's blockade of calcium influx, leads to vasorelaxation. In animal models of ischemia, bepridil and other calmodulin inhibitors show antiarrhythmic efficacy following reperfusion. Additionally, interfering with calmodulin's role in sympathetic nerve terminal function may help to limit the ischemia-induced catecholamine release that contributes to arrhythmogenesis. Bepridil shows a lidocaine-like fast kinetic block of inward sodium current (as distinct from the slow or intermediate kinetic inhibition expressed by encainide or quinidine, respectively). This inhibition is pH-dependent; activity is expressed to a greater degree at lower pH levels. This, this potentially antiarrhythmic mechanism is activated by conditions of ischemia. Bepridil's blockade of outward potassium currents and its inhibition of sodium-calcium exchange increase action potential duration and ventricular refractoriness, prolong the QT interval, and form the basis for a class III antiarrhythmic mechanism. Because hypokalemia also prolongs the QT interval, the addition of bepridil in the presence of hypokalemia can lead to excessive prolongation. Bepridil both increases myocardial oxygen supply through coronary vasodilation and decreases myocardial oxygen demand through mild heart rate and afterload reduction, and shows potential antiarrhythmic activity through class IB, III, and IV mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology of bepridil. 137 85

We examined the anti-infarct effect of ischemic preconditioning in the rat heart. All hearts were subjected to 30 min of regional coronary ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium. The control group had an average infarct size of 31% of the risk zone. Three 5-min cycles of preconditioning ischemia limited the infarct size to 3.7%. Neither the adenosine receptor blocker PD 115,199 nor the ATP-sensitive potassium channel blocker, glibenclamide, could block this protection. Intracoronary adenosine A1-receptor agonist 2-chloro-N6-cyclopentyladenosine offered a significant anti-infarct protection to the isolated rat heart, however. Although one 5-min cycle of preconditioning did not protect the rat heart from infarction (31% infarction in risk zone), it did attenuate arrhythmias. We conclude that 1) the rat heart can be preconditioned, which argues against mitochondrial adenosinetriphosphatase being the mechanism of preconditioning; 2) the threshold for preconditioning is higher in rat than rabbit or dog; 3) a role for adenosine in preconditioning was only partially supported; and 4) a role for ATP-sensitive potassium channels was not supported.
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PMID:Ischemic preconditioning protects against infarction in rat heart. 141 59


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