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)

We used metabolic, enzymatic, and functional end points to compare the protective properties of continuous warm and intermittent cold cardioplegic infusion in isolated, blood-perfused rat hearts. After excision, hearts (n = 12 per group) were preserved for 3 hours by one of the following cardioplegic procedures: (1) continuous infusion of warm (37 degrees C) blood cardioplegic solution prepared by mixing Fremes' solution with rat arterial blood in a ratio of 1:4, (2) continuous infusion of warm (37 degrees C) crystalloid cardioplegic solution prepared by mixing Fremes' solution with bicarbonate buffer solution in a ratio of 1:4, or (3) intermittent infusion of cold (20 degrees C) St. Thomas' Hospital cardioplegic solution number 2 infused for 3 minutes every 30 minutes during a 3-hour period of ischemia. In the continuous-infusion cardioplegic groups, the solution was infused through the aorta at a flow rate of 0.8 ml.min-1.gm-1 heart. At the end of the 3-hour preservation period, myocardial sodium-potassium adenosine triphosphatase activity (an index of ion-exchange activity) was assessed in six hearts in each group. The remaining hearts in each group were then aerobically perfused at 37 degrees C with arterial blood (from a support rat) for a further 50 minutes, during which time they were atrially paced at 320 beats/min. At the end of this period, left ventricular developed and end-diastolic pressures were assessed with an intraventricular balloon; the hearts were then freeze-clamped and taken for the measurement of tissue adenosine triphosphate and creatine phosphate content. Hearts (n = 6) aerobically perfused with blood for 50 minutes (no cardioplegic infusion) served as control preparations. At a balloon volume of 180 microliters, the mean final values for left ventricular developed pressure in the continuous warm blood, continuous warm crystalloid, and intermittent cold cardioplegic groups were 98 +/- 5 mm Hg (p < 0.05), 70 +/- 5 mm Hg, and 78 +/- 5 mm Hg, respectively. This was compared with 122 +/- 5 mm Hg in control hearts (p < 0.05 vs the rest). For left ventricular end-diastolic pressure, the corresponding values were 33 +/- 3 mm Hg, 32 +/- 6 mm Hg, and 14 +/- 4 mm Hg (p < 0.05), respectively. The control value was 16 +/- 3 mm Hg (p < 0.05 vs continuous warm blood and continuous warm crystalloid groups). Tissue content of adenosine triphosphate was similarly reduced to approximately 50% of control values in all groups, and creatine phosphate content fully recovered in all groups. Sodium-potassium adenosine triphosphatase activity was poorly preserved in continuous warm crystalloid-treated hearts (0.012 +/- 0.003 vs 0.030 +/- 0.008 mumol inorganic phosphate-mg-1.min-1.
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PMID:Continuous warm versus intermittent cold cardioplegic infusion: a comparison of energy metabolism, sodium-potassium adenosine triphosphatase activity, and postischemic functional recovery in the blood-perfused rat heart. 880 Jan 70

Motor and sensory nerve conduction velocities (MNCV and SNCV) were reduced in the sciatic nerve of rats after 4 weeks of untreated streptozotocin-induced diabetes, and declined further during the following 4 weeks. Treating diabetic rats with the novel peptide HP228 had no effect on the decline of MNCV after the first 4 weeks of diabetes but attenuated the decline in SNCV. HP228 treatment also prevented any further decline in MNCV or SNCV between weeks 4 and 8 of diabetes. Consequently, at the conclusion of the study, the nerve conduction velocities (NCVs) in treated rats were significantly (both P < .001) higher than in untreated diabetic rats. Reduced nerve homogenate Na+,K+-adenosine triphosphatase (ATPase) activity in diabetic rats was significantly (P < .05) increased by HP228 but remained significantly (P < .05) lower than in untreated controls. HP228 treatment also reduced nerve Na+,K+-ATPase activity of control rats compared with untreated controls (P < .05). There was no effect of HP228 on the hyperglycemia, nerve polyol accumulation, myo-inositol depletion, reduced nerve laser Doppler blood flow, thermal hypoalgesia, or reduced mean axonal caliber in diabetic rats or on any of these parameters in control rats. These data demonstrate that a novel peptide may protect against the slowing of nerve conduction in prolonged diabetes and that the mechanism of action is unrelated to aldose reductase inhibition, prevention of nerve ischemia, or axonal atrophy. HP228 may prove a potential therapeutic agent for the treatment of prolonged diabetic neuropathy.
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PMID:Effects of the peptide HP228 on nerve disorders in diabetic rats. 962 61

Intracellular-type electrolyte solutions were introduced into organ preservation to prevent K+ efflux and Na+ and Cl- influx into cells and cell swelling during cold ischemia. We studied cation accumulation in the interstitial space by microdialysis, during rat liver cold storage and after flush-out with high-K+ and low-K+ solutions. The effect of Na+ and K+ on graft function and survival was studied in an isolated perfused liver model and an orthotopic transplantation model after rat liver storage in iso-osmolar high-K+ and low-K+ solutions. After 24 hours of cold ischemia [Na+]o dropped from 136 +/- 2 mmol/L to 91.8 +/- 1.1 mmol/L, and [K+]o increased from 5.9 +/- 0.1 mmol/L to 12.2 +/- 1.6 mmol/L (P < .001 vs. control). [Na+]o and [K+]o after flush-out did not equilibrate with [Na+]sol and [K+]sol after 24 hours of cold storage. Rat livers preserved in low-K+ solutions produced significantly more bile during isolated reperfusion and released less alanine transaminase, aspartate transaminase, and lactate dehydrogenase into the reperfusion medium than high-K+ solutions. Rat liver survival after 14 hours of preservation was higher in low-K+ solutions (13 of 13) than in high-K+ solutions (7 of 13). Those studies indicate that during cold storage of rat livers, transmembraneous Na+-K+ sodium-potassium exchange might not follow the 3:2 stochiometry of a sole sodium-potassium exchange via Na+-K+ sodium-potassium adenosine triphosphatase (ATPase), and that low-K+ solutions might improve graft function and survival after rat liver preservation.
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PMID:Interstitial accumulation of Na+ and K+ during flush-out and cold storage of rat livers: implications for graft survival. 979 18

We clarified the role of K(ATP) channels in the mechanism of ischemic preconditioning by using K(ATP) channel opener, nicorandil, and K(ATP) channel inhibitor, glibenclamide. Forty anesthetized dogs were divided into five groups: (a) control (C), (b) ischemic preconditioning (PC), (c) intravenous infusion of nicorandil before PC (Ni), (d) glibenclamide pretreated with PC (Gl + PC), and (e) glibenclamide pretreated with Ni (Gl + Ni). All groups were followed by 60-min ischemia and 60-min reperfusion and analyzed by the biochemical procedures. At the end of 60-min reperfusion, percentage of segment shortening in C indicated paradoxic bulging. This value was significantly recovered in PC and Ni, but it was still negative in Gl + PC and Gl + Ni. Ca2+ -adenosine triphosphatase (ATPase) activity of sarcoplasmic reticulum (SR) was significantly decreased in C. In PC and Ni, this activity was significantly maintained; however, in Gl + PC and Gl + Ni, it was similar to that in C. State III respiration of mitochondria showed similarity to the changes in SR. These results indicated that the K(ATP) channel opener enhanced the effects of ischemic preconditioning, and its blockade abolished these phenomena. We conclude that the ATP-sensitive potassium channel may play one of key roles in the mechanisms of ischemic preconditioning in the dog model.
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PMID:The role of ATP-sensitive potassium channels in the mechanism of ischemic preconditioning. 1047 Oct 6

BACKGROUND: Hydrogen peroxide (H(2)O(2)) in high concentrations has been implicated in heart dysfunction attributable to ischemia-reperfusion. Although H(2)O(2) is also known to increase the intracellular concentration of Ca(2+) ([Ca(2+)](i)) in cardiomyocytes, the mechanisms for such a change are not clear. In this study, the sources and mechanisms of increase in [Ca(2+)](i) caused by high concentrations of H(2)O(2) in cardiomyocytes were explored. METHODS AND RESULTS: Cardiomyocytes were isolated from adult male Sprague-Dawley rats. Cell viability was examined by trypan blue exclusion test. [Ca(2+)](i) was measured by employing cell suspension at room temperature and Fura-2 fluorescence technique. Incubation of cells with 0.25-l mmol/L H(2)O(2) increased [Ca(2+)](i) in a time- and concentration-dependent manner. Catalase attenuated the H(2)O(2)-induced increase in [Ca(2+)](i) significantly, whereas mannitol showed no effect. Neither the presence of verapamil, a sarcolemmal Ca(2+) channel blocker, nor the removal of Ca(2+) from the medium produced any significant reduction in the H(2)O(2)-induced increase in [Ca(2+)](i). Conversely, treatment of cardiomyoctes with staurosporin, a protein kinase C inhibitor, thapsigargin, a sarcoplasmic reticulum Ca(2+)-pump adenosine triphosphatase inhibitor, as well as ryanodine, a sarcoplasmic reticulum Ca(2+)-release channel blocker, markedly prevented the 0.5-mmol/L H(2)O(2)-induced increase in [Ca(2+)](i). The responses of cardiomyoctes to H(2)O(2) and other Ca(2+)-mobilizing agents, such as KCl or adenosine triphosphate, were additive. No changes in cardiomyocyte viability were seen on incubation with 0.5 and 1 mmol/L H(2)O(2). Perfusion of the isolated heart with H(2)O(2) (0.1-0.5 mmol/L) depressed the left ventricular developed pressure, rate of contraction, and rate of relaxation, whereas the left ventricular end-diastolic pressure was increased. CONCLUSIONS: These results indicate that formation of H(2)O(2) under pathophysiological conditions such as ischemic heart disease may induce changes in Ca(2+) homeostasis in cardiomyocytes and may induce contractile dysfunction. Furthermore, the sarcoplasmic reticulum involving a protein kinase C-mediated mechanism appears to be the main site of action of H(2)O(2) in cardiomyocytes.
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PMID:Mechanisms of Hydrogen Peroxide-Induced Increase in Intracellular Calcium in Cardiomyocytes. 1068 23

We tested the hypothesis that ischemia alters sarcoplasmic reticulum (SR) Ca2+ transport by oxidizing regulatory thiols on ryanodine receptors (RyRs), and that membrane-permeable sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitors protect against ischemia-induced oxidation and explain in part, the therapeutic actions of captopril. Ca2+ uptake and adenosine triphosphatase (ATPase) activity was measured from SR vesicles isolated from control or ischemic dog and human ventricles and compared with or without sulfhydryl reductants. The rate and amount of Ca2+ uptake was lower for canine ischemic SR compared with control (6.5 +/- 0.2 --> 18.5 +/- 1.1 nmol Ca2+/mg/min and 123.1 +/- 4.7 --> 235.0 +/- 17.3 nmol Ca2+/mg; n = 8 each). Captopril, dithiothreitol (DTT), glutathione (GSH), and L-cysteine increased the rate and amount of Ca2+ uptake by canine and human ischemic SR vesicles by approximately 50%. Reducing agents had no effect on Ca2+- ATPase activity in either canine control or ischemic (approximately 40% less than control) SR. Captopril was as potent as DTT at reversing the oxidation of skeletal and cardiac RyRs induced by reactive disulfides (RDSs) or nitric oxide (NO). In neonatal rat myocytes, RDSs or NO triggered SR Ca2+ release and increased cytosolic Ca2+, an effect reversed by captopril and DTT but not GSH or cysteine. Pretreatment of myocytes with captopril (exposure and then wash) inhibited Ca2+ elevation elicited by RDSs or NO, indicating that captopril is an effective, membrane-permeable intracellular reducing agent. Thus, net SR Ca2+ accumulation is reduced by ischemia in part due to the oxidation of thiols that gate RyRs, an effect reversed by captopril.
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PMID:Cardiac ischemia oxidizes regulatory thiols on ryanodine receptors: captopril acts as a reducing agent to improve Ca2+ uptake by ischemic sarcoplasmic reticulum. 1106 27

The aim of our work was to study the changes in activity, abundance and distribution of sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) in membranes of cortical tubular cells in an in vivo model of ischemic injury without reperfusion. Na+,K+-ATPase, alkaline phosphatase (AP) activities and their distribution in membranes isolated from renal cortex using a Percoll gradient were studied after different ischemic periods. Na+,K+-ATPase alpha-subunit protein abundance was analysed by Western-blot. Plasma urea and cortical adenosine 5' triphosphate (ATP) were also measured. In cortical homogenates 5 min of ischemia promoted a diminution in ATP content. Na+,K+-ATPase activity diminished after 40 min and AP after 100 min of ischemia. Na+,K+-ATPase activity in the Percoll gradient fractions after 5 min peaked at a higher density and was significantly decreased after 40 min. AP activity was decreased in typically enriched apical membranes after both times of ischemia. At each time studied Na+,K+-ATPase abundance was increased in cortical homogenates and membranes. Our results showed opposite effects of ischemia on Na+,K+-ATPase activity and abundance. Increased levels of Na+,K+-ATPase protein were observed. The enzyme would be rapidly delivered to membrane domains and become inactivated as ischemia persists.
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PMID:Cortical Na+,K+-ATPase activity, abundance and distribution after in vivo renal ischemia without reperfusion in rats. 1152 37

Glucocorticoids have been reported to aggravate ischemic neuronal damage. Because energy failure is a crucial factor in the development of ischemic neuronal injury, the effects of dexamethasone on histologic outcome and energy metabolism were investigated in gerbil brain. Dexamethasone (3 microg, i.c.v.) was administered 1 h prior to ischemia, and its effect on delayed neuronal death caused by 2 min of bilateral common carotid artery occlusion was observed in hippocampal CA1 pyramidal neurons. The brain concentration of ATP after various durations of decapitation ischemia was determined, and the effect of dexamethasone (3 microg, i.c.v.) was examined. Na+,K+-activated adenosine triphosphatase (Na+,K+-ATPase) activity was evaluated after the administration of the agent. Forebrain ischemia for 2 min produced neuronal damage in animals pretreated with dexamethasone, although neuronal damage was not observed in vehicle-injected animals. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP concentration to 44% and 15% of the basal level, respectively. Dexamethasone attenuated the ischemia-induced reduction in ATP, and the values were 58% and 25% of the basal level, respectively. Na+,K+-ATPase activity at pH 6.7 was suppressed to 47% by dexamethasone treatment (3 microg, i.c.v.), whereas the activity at pH 7.4 was not influenced by the agent. The results show that a contributing factor to the aggravation of ischemic neuronal damage may be a disturbance in Na+,K+-ATPase despite adequate levels of ATP.
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PMID:Dexamethasone reduces energy utilization in ischemic gerbil brain. 1155 63

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of septic shock and ischemia and reperfusion. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na /K adenosine triphosphatase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of reactive oxygen species. In addition, reactive oxygen species are potent triggers of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-adenosine 5'-diphosphate ribosyl synthetase, and eventual severe energy depletion of the cells. Pharmacologic evidence suggests that the peroxynitrite-poly-adenosine 5'-diphosphate ribosyl polymerase pathway contributes to the cellular injury in shock and endothelial injury. Treatment with superoxide dismutase mimetics, which selectively mimic the catalytic activity of the human superoxide dismutase enzymes, has been shown to prevent the cellular energetic failure associated with shock and ischemia-reperfusion and to prevent tissue damage associated with these conditions. In this article, we will briefly review the role of superoxide in septic shock and ischemia-reperfusion injury. We hope to present evidence to support the potential development of superoxide dismutase mimetics as novel and effective agents in the area of critical care medicine.
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PMID:Therapeutic potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine. 1254 74

In the present study to evaluate the effects of ischemia on sodium-potassium adenosine triphosphatase (Na(+)-K+ ATPase) alpha1 subunit (alpha6F) expression in the glia, the immunodensities of both Na(+)-K+ ATPase and the glial fibrillary acidic protein in the hippocampus were measured and analyzed. In the sham hippocampus, alpha6F immunoreactivity was mainly observed in the both the molecular layer and the polymorphic layer of dentate gyrus. At 30 min after ischemic insult, the alpha6F immunoreactivity was markedly decreased in the molecular layer of the dentate gyrus, in contrast to the appearance of this immunoreactivity in the hilar neurons. Up to 12 h after ischemic insult, the alpha6F immunoreactivity was re-enhanced in the molecular layer of dentate gyrus. In addition, the alpha6F immunoreactivity appeared slightly in the glial components in the hippocampal region. Four days after ischemia-reperfusion, the intensity of alpha6F immunoreactivity in the glial cells was highest. At this time point, strong alpha6F immunoreactivity was colocalized with GFAP immunoreactivity in the strata radiatum of the CA1 and the molecular layer of the dentate gyrus. These results suggest that the enhancement of alpha6F immunoreactivity may be a compensatory response to regulate the ion homeostasis in the brain. In addition, the maintenance of Na(+)-K+ ATPase activity in the astrocytes may explain the resistant characteristics of these cells to ischemic insults.
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PMID:Changes of glial Na+-K+ ATPase (alpha 1 subunit) immunoreactivity in the gerbil hippocampus after transient forebrain ischemia. 1449 68


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