Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the uptake of labeled dexamethasone (3H-Dex) or methylprednisolone (3H-MP) in isolated perfused cat hearts during the first hour of acute myocardial ischemia. Considerable amounts of 3H-Dex and 3H-MP were taken up by the plasma membrane (F1) fraction in control, border zone, and ischemic myocardial tissue. Lesser amounts were incorporated into the remaining cell fractions. A gradient of glucocorticoid uptake was observed that decreased from control tissue to ischemic tissue in all subcellular fractions (i.e., F1 to F5). Accordingly, supernatant fraction (S) to particulate (P) ratios of labeled glucocorticoid uptake increased from control to ischemic tissue, indicating that myocardial cell damage resulted in a decrease in glucocorticoid-binding capacity in subcellular fractions obtained from ischemic tissue. The activity of 5'-nucleotidase (5'ND), a plasma membrane marker in myocardial cells, also decreased from normal to ischemic tissue. Furthermore, we found that uptake of 3H-MP and 3H-Dex was associated with the retention of 5'ND activity in F1 fractions of both border zone and ischemic tissue. Similar protection of plasma membrane integritg occurred in the supernatant fraction as determined by changes in S/P ratios of 5'ND activity. These data provide support for the concepts that (1) plasma membrane changes occur soon after acute myocardial ischemia, and (2) the mechanism by which glucocorticoids exert a protective effect in myocardial ischemia may be related to membrane stabilization.
...
PMID:Localization of glucocorticoid uptake in normal and ischemic myocardial tissue of isolated perfused cat hearts. 97 52

Myocardial uptake of dexamethasone (Dex) or methylprednisolone (MP) was studied using tritiated tracers in isolated perfused cat hearts during acute myocardial ischemia. Considerable amounts of Dex and MP were incorported into the plasma membranes in control, border-zone, and ischemic myocardium. Lesser amounts were bound to the remaining subcellular organelles. A gradient of the glucocorticoid uptake was observed decreasing from control myocardium to ischemic myocardium in all subcellular fractions. By the first hour of ischemia, the myocardial plasma membranes underwent marked depletion of activity of 5'-nucleotidase, a plasma membrane marker enzyme, indicating early loss of plasma membrane integrity in acute myocardial ischemia. The incorporation of Dex or MP into the plasma membranes resulted in a significant decrease in loww of 5'-nucleotidase activity of the plasma membranes in the border-zone and ischemic myocardium. The data provide direct evidence 1) to support a membrane stabilizing action of glucocorticoids, and 2) to focus on the plasma membranes as a potentially important site of protection during the early phase of acute myocardial ischemia.
...
PMID:Preservation of myocardial membrane integrity in the early phase of acute myocardial ischemia. 103 5

The present study was undertaken to determine whether significant breakdown of adenine nucleotides to purine bases and oxypurines occurred in mitochondria following myocardial ischemia and ischemia followed by reperfusion, and whether allopurinol prevented this effect. The adenine nucleotides adenosine, hypoxanthine, xanthine and uric acid were measured in the mitochondria and the results suggest that breakdown did occur. Malondialdehyde concentration was determined to gauge lipid peroxidation. This substance did not increase during ischemia or reperfusion, but did so in the presence of allopurinol. Xanthine dehydrogenase was converted to xanthine oxidase during reperfusion and the activity of both enzymes were inhibited by allopurinol. The results also suggested the presence of a mitochondrial 5'-nucleotidase. We conclude that significant breakdown of adenine nucleotide took place in myocardial mitochondria during ischemia and ischemia followed by reperfusion and that allopurinol may have a protective effect.
...
PMID:Purine and oxypurine production in mitochondria of ischemic and reperfused myocardium. 261 53

To investigate whether slow Ca2+ channel blockers protect against development of changes in properties of the sarcolemma and in the tissue ultrastructure during myocardial ischemia, nifedipine was administered prior to occlusion (up to 3 hours) of the left anterior descending coronary artery in anesthetized pigs. Intravenous doses which reduced arterial blood pressure by 20-25%, had no effect on the time-dependent reduction of Ca2+-calmodulin and cyclic AMP-dependent 32P incorporation into sarcolemmal phospholamban-like protein. Nifedipine blocked the reduction in the activity of sarcolemmal 5'-nucleotidase. Nifedipine had no significant effect on the long-chain fatty acylcarnitine accumulation in sarcolemma. A marked delay in the appearance of ultrastructural indicators of irreversible tissue injury in subepicardial myocardium was observed, when nifedipine was infused. Particularly the reduced appearance of electron-dense bodies in mitochondria suggested a reducing effect of nifedipine on cellular net gain of Ca2+. Apparently, ischemia-induced loss of the ability of the proteinkinases to incorporate phosphate into sarcolemmal phospholamban-like protein is not a process secondary to Ca2+ overload of the myocardium. The involvement of accumulation of long-chain fatty acylcarnitine within the sarcolemma may also be excluded. The membrane defect as indicated by a change in phosphorylation-mediated control of Ca2+ transport may itself be associated with the development of ischemia (-reperfusion)-induced Ca2+ overload.
...
PMID:The effect of nifedipine on ischemia-induced changes in the biochemical properties of isolated sarcolemmal vesicles and the ultrastructure of myocardium. 303 May 20

The enhancement of ATP regeneration following global myocardial ischemia in dogs by both ATP catabolic enzyme blockade and precursor infusion was investigated. The breakdown of AMP to adenosine is catalyzed by 5'-nucleotidase and this enzyme was inhibited during the ischemic period with either concanavalin A (Con A, 3 mg/kg) or alpha, beta-methyleneadenosine 5'-diphosphate (AMP-CP, 250 microM). To provide additional ATP precursors, adenine (30 mg/kg) and ribose (25 mg/kg) (A/R) were also infused into the coronary vasculature during ischemia and recovery on cardiopulmonary bypass. Left ventricular myocardial ATP levels in control animals decreased to 52% of preischemic values during aortic cross clamping, but ATP levels in dogs treated with AMP-CP + A/R fell to only 67% of preischemic values (P less than 0.05). During reperfusion, ATP levels in Con A + A/R (3.43 +/- 0.26 mumol/g wet wt) and AMP-CP + A/R (3.77 +/- 0.42) treated animals were higher than values found in control dogs (2.73 +/- 0.16, P less than 0.05). Infusions of A/R alone without enzyme inhibition did not increase ATP regeneration. The adenine nucleotide energy charge ratio was also increased by enzyme blockade with either inhibitor when combined with precursor infusion. On bypass, left ventricular myocardial blood flow (measured by the microsphere technique) was increased by 140% (P less than 0.01) over control values in all groups receiving A/R; therefore, enhanced ATP levels were not merely the result of increased flow. Renal blood flow was not adversely affected by this combination of drugs as has been previously found with adenosine infusion and inhibition of adenosine catabolism.
...
PMID:Prevention of ATP catabolism during myocardial ischemia: a preliminary report. 683 14

Recent research has shown that repeated brief myocardial ischemia (RBMI) can increase the tolerance of myocardium to a subsequent sustained ischemia and have protective effects on myocardial cells. With the isolated rat heart Langendorff model, we investigated the effects of RBMI on myocardial morphology, systolic function, coronary flow rates (CFR), myocardial membrane phospholipid (PL) content and its marker enzyme's activity (5'-AMPase). The results showed: After ischemia-reflow, the HR, LVP and CFR in control and experimental groups had no significant difference (P > 0.05). But the PL content and specific activity of 5'-AMPase were significantly higher in the experimental group than that in control group (P < 0.01, P < 0.05). And the observations of ultrastructure suggested that the myocardium of the experimental group was preserved better than that in control group. It was also shown that RBMI had protective effects on myocardial membrane structure, and however effective had no relation to CFR.
...
PMID:[Experimental studies of protective effects of ischemic myocardium preconditioning and its mechanism]. 765 38

Adenosine methylene diphosphate (AMPCP), a 5'-nucleotidase inhibitor, was evaluated as an adjunct to cold crystalloid cardioplegic myocardial protection. Cardiopulmonary bypass (CPB) was instituted at 28 degrees C in two groups of mongrel dogs (each, n = 6). Myocardial ischemia was induced for 150 min by aortic cross clamping. Crystalloid cardioplegia (4 degrees C) was infused into the aortic root at 15 ml/kg/20 min in the control group (CP). The experimental group (CP + AMPCP) received identical doses of cardioplegia supplemented with 250 microM AMPCP. While on CPB, the mean arterial pressure was 70 mm Hg and the myocardial temperature ranged from 16 to 22 degrees C. Hemodynamic parameters were recorded prior to institution of CPB and at 15 and 45 min following the termination of CPB. Starling curves were constructed for cardiac index (CI), mean arterial pressure (MAP), mean left ventricular pressure (LVP), +dP/dt and -dP/dt at each time point for left atrial pressures between 5 and 12.5 mm Hg. The area under each curve was calculated and expressed as a percentage of prebypass values. Statistical analysis was performed with Student's two-tailed t test. The data demonstrate that although recovery of CI, MAP, heart rate, and LVP was similar in both groups, statistically significant improvement in recovery of myocardial compliance (-dP/dt) and systolic function (+dP/dt) was seen with AMPCP. The addition of the 5'-nucleotidase inhibitor, AMPCP, to cold crystalloid cardioplegia enhances postischemic myocardial performance in vivo and may be useful during prolonged periods of global myocardial ischemia.
...
PMID:5'-Nucleotidase inhibition enhances postischemic myocardial performance. 815 30

Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible for conversion of high-energy phosphates to their the diffusible precursors, may help to explain age-related differences in tolerance of global myocardial ischemia. Postischemic function and high-energy phosphate content were measured in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month), and 6 to 12 months old (adult). Hearts in each age group were subjected to 60 minutes of ischemia at 34 degrees C either with no cardioplegia, with unmodified St. Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibitor. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pentoxifylline to St. Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total nondiffusible nucleotide levels to control values and improved recovery of cardiac output and developed pressure compared with results with unmodified St. Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the older age groups. In 1-month-old hearts, St. Thomas' Hospital cardioplegia improved recovery compared with recovery after unprotected ischemia, but no incremental improvement in function or high-energy stores was seen with addition of pentoxifylline. The lack of effect of pentoxifylline on neonatal hearts suggest that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the improved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benefits of low 5'-nucleotidase activity occurring naturally in the neonate.
...
PMID:Developmental differences in myocardial protection in response to 5'-nucleotidase inhibition. 830 72

The effect of 5'-nucleotidase inhibitor (AMP-C) and xanthine oxidase inhibitor (Allopurinol: ALLO) on myocardial functional recovery and the restoration of myocardial high energy phosphates after 15 min of normothermic global ischemic insult, was studied in the isolated isovolemic Langendorff rat heart model. Fifty nine rats were divided into 4 groups: Group I; saline, Group II; AMP-C plus ALLO, Group III; AMP-C, Group IV; ALLO. Intermittent infusion of drugs was delivered in 3 ml of solution at 5 min intervals during ischemia. Percent recovery of left ventricular systolic function was as follows: Group I; 74.2 +/- 3.6%, Group II; 87.7 +/- 1.7%, Group III; 83.5 +/- 3.1%, Group IV; 86.4 +/- 2.6%. Improved recovery was statistically significant only in Group II (p < 0.05 vs Group I). Suppression of reactive hyperemia was seen with reperfusion in the groups which had been treated with AMP-C (i.e., Groups II and III). Myocardial adenine nucleotides and purines were measured in 6 hearts in each group using high performance liquid chromatography. Myocardial ATP levels was 0.89 +/- 0.16 nmol/mg left ventricular wet weight in Group I, 1.37 +/- 0.12 in Group II (p < 0.05 vs Group I), 1.42 +/- 0.17 in Group III (p < 0.05) and 1.17 +/- 0.15 in Group IV. This study demonstrates that intermittent infusion of AMP-C plus ALLO during global myocardial ischemia results in improved myocardial functional recovery and improved preservation of high energy phosphates.
...
PMID:Evaluation of the effectiveness of 5'-nucleotidase inhibitor and allopurinol in myocardial ischemia. 835 99

The purpose of this study was to determine the roles of cytosolic and ecto 5'-nucleotidase in myocardial ischemia-induced increases in interstitial fluid (ISF) adenosine. Pentobarbital anesthetized, open chest pigs were instrumented with two microdialysis fibers in the distally perfused bed of the left anterior descending (LAD) coronary artery to estimate ISF metabolites. Fibers in control hearts were perfused with standard Krebs buffer. In two additional groups, after collecting one dialysate sample with normal Krebs, fibers were perfused with buffer supplemented with either L-homocysteine thiolactone (5 mM) or the ecto 5'-nucleotidase inhibitor alpha, beta-methylene adenosine 5'-diphosphate (AOPCP, 5 mM). Hearts were then submitted to 60 minutes LAD occlusion and two hours reperfusion. Dialysate nucleosides and AMP were measured by high performance liquid chromatography. The local delivery of homocysteine did not alter preischemic dialysate adenosine concentration (0.30 +/- 0.04 microM) compared to pre-homocysteine infusion (0.39 +/- 0.04 microM) or control hearts (0.36 +/- 0.04 microM), but AOPCP significantly decreased preischemic dialysate adenosine levels (from 0.36 +/- 0.02 to 0.14 +/- 0.03 microM). During LAD occlusion both homocysteine and AOPCP reduced dialysate levels by approximately 50%. At 30 minutes ischemia dialysate adenosine concentrations were 19.47 +/- 2.72, 11.41 +/- 2.44, and 7.93 +/- 1.01 microM in control, homocysteine, and AOPCP hearts, respectively. AOPCP significantly increased dialysate AMP levels; at 60 minutes ischemia AMP levels were 6.22 +/- 2.97 microM in control hearts and 38.60 +/- 5.69 microM in AOPCP treated hearts. These results suggest that both cytosolic and ecto 5'-nucleotidase contribute to ischemia-induced increases in ISF adenosine in porcine myocardium.
...
PMID:Evidence that cytosolic and ecto 5'-nucleotidases contribute equally to increased interstitial adenosine concentration during porcine myocardial ischemia. 1042 38


1 2 Next >>

---