Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors have previously shown that atrial natriuretic peptide (ANP) mediates its cellular effects in part by changes in Ca2+ homeostasis in kidney cortex and that Ca2+ + Mg2+ ATPase is linked to ANP receptors, being reciprocally modulated by the guanylate cyclase system. The present study was designed to examine the status of this coupling in diabetes-induced congestive heart failure and the effect of its alterations on the functional integrity of the renal cell. Ca2+ + Mg2+ ATPase and guanylate cyclase were tested in hypertensive-diabetic rats (D + H), which develop congestive heart failure (CHF) at ten weeks following streptozotocin (65 mg/kg) injection and abdominal aortic constriction. The ATPase activity was measured by the release of 32P from [gamma-32P]ATP in the medium. While the guanylate cyclase activity was decreased very rapidly in the hypertensive-diabetic group, the sensitivity of the Ca2+ pump to ANP was increased at an early stage (three weeks) and decreased at a late stage (ten weeks) of CHF. The authors conclude that a defect in coupling between the Ca2+ pump and the ANP-receptor system as observed in the D + H group may contribute to the development of nephropathy and CHF.
 ...
PMID:Renal Ca2+ + Mg2+ ATPase in congestive heart failure due to diabetes. 810 29

To characterize the sodium transport defect responsible for salt wasting in obstructive nephropathy, the major sodium transporters in the medullary thick ascending limb (mTAL), the apical Na-K-2Cl cotransporter and the basolateral Na-K-ATPase, were studied in fresh suspensions of mTAL cells and outer medulla plasma membranes prepared from obstructed and untreated kidneys. Oxygen consumption (QO2) studies in intact cells revealed marked reductions in the inhibitory effects of both furosemide and ouabain on QO2 in cells from obstructed, as compared with control animals, indicating a reduction in activities of both the Na-K-2Cl cotransporter and the Na-K-ATPase. Saturable [3H]bumetanide binding was reduced in membranes isolated from obstructed kidneys, but the Kd for [3H]bumetanide was unchanged, indicating a decrease in the number of functional luminal Na-K-2Cl cotransporters in obstructed mTAL. Ouabain sensitive Na-K-ATPase activity in plasma membranes was also reduced, and immunoblots using specific monoclonal antibodies directed against the alpha and beta subunits of rabbit Na-K-ATPase showed decreased amounts of both subunits in outer medullas of obstructed kidney. A significant decrease in [3H]bumetanide binding was detected after 4 h of ureteral obstruction, whereas Na-K-ATPase activity at this time was still not different from control. We conclude that ureteral obstruction reduces the amounts of both luminal Na-K-2Cl cotransporter and basolateral Na-K-ATPase in mTAL of obstructed kidney and that these reductions contribute to the salt wasting observed after release of obstruction.
 ...
PMID:Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy. 838 Aug 11

Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
 ...
PMID:Aldose reductase and its inhibition in the control of diabetic complications. 845 42

Hypertension is a complication of reflux nephropathy commonly occurring during adolescence and young adult life. We studied cellular sodium transport in an adolescent cohort with this condition as abnormal sodium transport is a feature of human hypertension. Thirty males and 52 females with reflux nephropathy, (median age 20.3 years) had erythrocyte ouabain sensitive sodium-potassium ATPase (Na/K ATPase) pump site number (Bmax) and red cell sodium concentration (RBC Na+) measured in 1988. Six years later, 55 of those had red cell sodium-lithium counter transport (LCT) measured. On both occasions, their renal function and blood pressure (BP) were determined. Bmax in the study group (median 10.3 nmol/l) was significantly less than that of controls (median 11.45 nmol/l). Nine patients who were diagnosed as having hypertension during the 6 year study period appeared to have a lower Bmax compared with that of normotensives in the group. RBC Na+ and LCT of the study group were not significantly different from that of controls. The Na/K ATPase activity is diminished, and sodium-lithium counter transport is unchanged in reflux nephropathy. Further study is needed to ascertain the link between these observations and the onset of high BP.
 ...
PMID:Abnormalities of erythrocyte sodium transport in reflux nephropathy. 888 May 62

The frequency of cardiovascular diseases in patients with end-stage renal disease (ESRD) is high, since hypotension, hyperlipidemia, advanced age, diabetes and other systemic diseases that may affect the heart are common in such patients. In addition to the pre-existing factors for cardiovascular disease, there are also predisposing factors that relate specifically to life on hemodialysis (HD). These include myocardial stress related to recurrent volume expansion and contraction, anemia, secondary hyperparathyroidism, excess or deficit of certain trace metals that may act as enzyme cofactors, and factors that inhibit myocardial ATPase. The prevalence, pathogenesis, and significance of these factors in ESRD patients are examined, and the potential roles of management are reviewed.
 ...
PMID:Cardiovascular complications in end-stage renal disease and hemodialysis patients. 904 18

A form of autosomal dominant polycystic kidney disease (ADPKD) similar in clinical features to human ADPKD occurs in the Persian cat. We characterized the morphologic and immunohistochemical features of this disease in a colony of affected cats. Complete postmortem examinations were performed on 11 normal and 22 affected cats ranging in age from 3 months to 10 years. Kidneys were evaluated by gross and histologic examinations, ultrastructure, lectin staining, bromodeoxyuridine immunochemistry for labeling index and immunochemistry for distribution of Na/K ATPase. Feline ADPKD was characterized by variable numbers of cysts in the renal cortex and medullar. Ultrastructural examination and lectin staining suggested that cysts arose from proximal and distal nephron segments. Bromodeoxyuridine labeling demonstrated increased proliferation of epithelium lining some cysts in young cats. Immunohistochemical staining showed variable translocation of Na/K ATPase from the basolateral membranes of cyst-lining cells to the cytoplasm or luminal membranes. Cystic renal disease commonly was associated with chronic tubulointerstitial nephritis and hepatobiliary hyperplasia and fibrosis. Focal hyperplasia of renal tubular epithelium, hepatic cysts, and cardiac lesions were present in some cats. Feline ADPKD shares many morphologic and pathogenetic features with human ADPKD.
 ...
PMID:Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats. 906 78

A series of experiments were conducted to determine whether the feeding of beef tallow compared with menhaden oil would affect renal cortex membrane composition, Na,K-ATPase activity, renal cholesterol uptake, and plasma lipoprotein cholesterol profile. BHE/cdb rats were used because they carry a genetic trait for non-insulin-dependent diabetes mellitus and are prone to develop diabetic nephropathy. Beef tallow feeding resulted in an increase in HDL cholesterol and an increase in Na,K-ATPase activity. The different fats also affected the arachidonic acid content of the membrane but not the membrane cholesterol content. These diet effects may explain why the development of renal disease in beef tallow-fed rats is delayed when compared with rats fed an equivalent amount of menhaden oil.
 ...
PMID:Differential hepatic and renal cholesterol levels in diabetes-prone BHE/cdb rats fed menhaden oil or beef tallow. 911 25

Diabetes mellitus induces a decrease in Na/K ATPase activity in man and animals, and this decrease plays a role in the development of diabetic neuropathy. Na/K ATPase is encoded by various genes, of which the ATP1 A1 gene is expressed predominantly in peripheral nerves and in erythrocytes. To investigate whether a polymorphism in the Na/K ATPase genes could explain the predisposition of some patients with insulin-dependent diabetes mellitus (IDDM) to develop polyneuropathy, a restriction fragment length polymorphism (RFLP) of the ATP1 A1 gene was studied together with erythrocyte Na/K ATPase activity in 81 Caucasian patients with more than 10 years' duration of IDDM. Associations with diabetic neuropathy, retinopathy and nephropathy were sought. Digestion of the first intron of the ATP1 A1 gene by the Bgl II restriction enzyme revealed a dimorphic allelism. Frequency of the restricted allele was 0.18 in this selected series (however, it was 0.10 in representative samples of IDDM patients and of normal subjects in our area). Mean erythrocyte Na/K ATPase activity was lower in diabetic patients than in 42 control subjects (292 +/- 10, vs 402 +/- 13 nmol Pi.mg protein-1.h-1, p < 0.0001) and was not related to HbA1c value or to diabetes duration. It was lower in the group of the 28 patients bearing the restricted allele (241 +/- 10 vs 319 +/- 11 nmol Pi.mg protein-1.h-1, p < 0.0001). Neuropathy was absent in 50 patients, mild in 15 and severe in 16. When classified accordingly the three groups of patients did not differ with respect to sex, age and duration of diabetes. The respective frequency of the restricted allele among the groups was 10, 73 and 81%, (p < 0.0001) and mean erythrocyte Na/K ATPase activity was respectively: 322 +/- 10.7 nmol Pi.mg protein-1.h-1, 268 +/- 15 and 229 +/- 17, (p < 0.001). A borderline association between renal status or retinal status and repartition of polymorphism and a borderline correlation between renal status and Na/K ATPase activity were found, but significance disappeared after checking for the presence or absence of neuropathy. IDDM patients bearing the ATP1 A1 variant detected by Bgl II RFLP are much more frequently affected by neuropathy (relative risk 6.5, with 95% CI 3.3-13). Identification of this risk factor may help to prevent this complication. It is suggested that the restricted allele is in linkage disequilibrium with a genomic mutation allowing diabetes to induce a greater impairment of Na/K ATPase activity which could in turn favour the development of neuropathy.
 ...
PMID:Association of diabetic neuropathy with Na/K ATPase gene polymorphism. 916 17

Long-term prospective studies comparing the effects of conventional and intensive insulin therapy have linked diabetic hyperglycemia to the development of diabetic retinopathy, nephropathy, and neuropathy. The mechanisms through which glucose metabolism leads to the development of these secondary complications, however, are incompletely understood. In animal models of diabetic neuropathy, the loss of nerve function in myelinated nerve fibers has been related to a series of biochemical changes. Nerve glucose, which is in equilibrium with plasma glucose levels, rapidly increases during diabetic hyperglycemia because glucose entry is independent of insulin. This excess glucose is metabolized in large part by the polyol pathway. Increased flux through this pathway is accompanied by the depletion of myo-inositol, a loss of Na/K ATPase activity and the accumulation of sodium. Supportive evidence linking these biochemical changes to the loss of nerve function has come from studies in which aldose reductase inhibitors block polyol pathway activity, prevent the depletion of myo-inositol and the accumulation of sodium and preserve Na/K ATPase activity, as well as nerve function. The kidney and red blood cells (RBCs) are two additional sites of diabetic lesions that have been reported to develop biochemical changes similar to those in the nerve. We observed that polyol levels in the kidney cortex, medulla, and RBCs increased two- to ninefold in rats following 10 weeks of untreated diabetes. Polyol accumulation was accompanied by a 30% decrease in myo-inositol levels in the kidney cortex, but no change in RBCs or the kidney medulla. Na/K ATPase activity was decreased by 59% in RBCs but was unaffected in the kidney cortex or medulla. Aldose reductase inhibitor treatment that preserved myo-inositol levels, Na/K ATPase, and conduction velocity in the sciatic nerve also preserved Na/K ATPase activity in RBCs. Our results suggest that the pathophysiologic mechanisms underlying diabetic neuropathy are different from those of diabetic nephropathy. Our results also suggest that RBCs maybe a surrogate tissue for the assessment of diabetes-induced changes in nerve Na/K ATPase activity.
 ...
PMID:Effect of the aldose reductase inhibitor tolrestat on nerve conduction velocity, Na/K ATPase activity, and polyols in red blood cells, sciatic nerve, kidney cortex, and kidney medulla of diabetic rats. 961 71

Despite the prevalence of essential hypertension, its underlying genetic basis has not been elucidated due to the complexities of its determinants. To identify a hypertension susceptibility gene, we used an approach that integrates molecular, transgenic, and genetic analysis using Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats ascertained for genotype and phenotype. To determine the role of the Dahl S Q276L alpha1 Na,K-ATPase gene variant, we developed transgenic Dahl S rats bearing the Dahl R wild-type (wt) alpha1 Na, K-ATPase cDNA directed by the cognate wt promoter region, Tg[wtalpha1]. Transgenic Dahl S rats exhibited less salt-sensitive hypertension, less hypertensive renal disease, and longer life span when compared with non-transgenic Dahl S controls. Total chromosome 2 linkage analysis of F2(SxR) male rats detects cosegregation of the alpha1 Na,K-ATPase locus with salt-sensitive hypertension. These data support the alpha1 Na,K-ATPase gene as a susceptibility gene for salt-sensitive hypertension in the Dahl S rat model, and provide the basis for the study of the alpha1 Na,K-ATPase locus in human hypertension.
 ...
PMID:The alpha1 Na,K-ATPase gene is a susceptibility hypertension gene in the Dahl salt-sensitiveHSD rat. 973 44


<< Previous 1 2 3 4 5 6 7 8 9 Next >>