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)

The progress of chronic renal failure (CRF) is characterized by the development of glomerular and tubular lesions. However, little is known about the expression of organic anions renal transporters. The objective of this work was to study, in rats with experimental CRF (5/6 nephrectomy), the expression of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) and their contribution to the pharmacokinetics and renal excretion of p-aminohippurate (PAH). Two groups of animals were used: Sham and CRF. Six months after surgery, systolic blood pressure and plasma creatinine concentrations were significantly higher in CRF groups. CRF rats showed a diminution in: the filtered, secreted and excreted load of PAH; the systemic clearance of PAH; the renal OAT1 expression; and the renal Na-K-ATPase activity. No remarkable modifications were observed in the OAT3 expression from CRF kidneys. The diminution in the systemic depuration and renal excretion of PAH may be explained by the decrease in its filtered and secreted load. The lower OAT1 expression in remnant renal mass of CRF rats or/and the lower activity of Na-K-ATPase might justify, at least in part, the diminished secreted load of this organic anion.
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PMID:Altered renal elimination of organic anions in rats with chronic renal failure. 1587 38

Preeclampsia is a pregnancy-specific syndrome that is the leading cause of maternal death during pregnancy in the developed world. In preeclampsia, a combination of immunological, genetic and environmental factors can lead to altered cytotrophoblast (CTB) invasion of the uterine wall, a process that is critical for normal placental development and pregnancy maintenance. Marinobufagenin (MBG) is an endogenous inhibitor of the sodium pump Na(+)/K(+) ATPase, and increased plasma MBG is associated with hypertension, chronic renal failure and preeclampsia. In the present study, the effects of MBG on CTB differentiation and invasion were investigated utilizing the first trimester extravillous CTB cell line SGHPL-4. MBG significantly inhibited SGHPL-4 proliferation in a dose-dependent manner. In addition, growth factor-induced migration and invasion were significantly inhibited by MBG treatment. These findings demonstrate that MBG impairs CTB differentiation along the invasive pathway. Elucidating the mechanisms by which MBG impairs placental development may increase our understanding of fetal and maternal pathologies associated with preeclampsia.
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PMID:Marinobufagenin impairs first trimester cytotrophoblast differentiation. 1645 53

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl(3)) through oral administration at 0, 0.1, 2 and 40mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40mg/kg LaCl(3) significantly inhibited the activity of Ca(2+)-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.
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PMID:Neurotoxicological consequence of long-term exposure to lanthanum. 1716 62

The present work was designed to study Na+ K+ ATPase alpha1-subunit phosphorylation in rats with chronic renal failure (CRF) in comparison with normal rats. Na+ K+ ATPase alpha1-subunit phosphorylation degree was measured by binding the McK-1 antibody to dephosphorylated Ser-23 in microdissected medullary thick ascending limb of Henle (mTAL) segments. In addition, the total Na+ K+ ATPase alpha1-subunit expression and activity were also measured in the outer renal medulla homogenates and membranes. CRF rats showed a higher Na+ K+ ATPase activity, as compared with control rats (18.95 +/- 2.4 vs. 11.21 +/- 1.5 micromol Pi/mg prot/h, p < 0.05), accompanied by a higher total Na+ K+ ATPase expression (0.54 +/- 0.04 vs. 0.27 +/- 0.02 normalized arbitrary units (NU), p < 0.05). When McK-1 antibody was used, a higher immunosignal in mTAL of CRF rats was observed, as compared with controls (6.3 +/- 0.35 vs. 4.1 +/- 0.33 NU, p < 0.05). The ratio Na+ K+ ATPase alpha1-subunit phosphorylation/total Na+ K+ ATPase alpha1-subunit expression per microg protein showed a non-significant difference between CRF and control rats in microdissected mTAL segments (2.11 +/- 0.12 vs. 2.26 +/- 0.18 NU, p = NS). The PKC inhibitor RO-318220 10(-6) M increased immunosignal (lower phosphorylation degree) in mTAL of CRF rats to 128.43 +/- 7.08% (p < 0.05) but did not alter McK1 binding in control rats. Both phorbol 12-myristate 13-acetate (PMA) 10(-6) M and dopamine 10(-6) M decreased immunosignal in CRF rats, corresponding to a higher Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23 (55.26 +/- 11.17% and 53.27 +/- 7.12% compared with basal, p < 0.05). In mTAL of CRF rats, the calcineurin inhibitor FK-506 10(-6) M did not modify phosphorylation degree at Ser-23 of Na+ K+ ATPase alpha1-subunit (100.21 +/- 3.00% compared with basal CRF). In control rats, FK 506 10(-6) M decreased the immunosignal, which corresponds to a higher Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23. The data suggest that the regulation of basal Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23 in mTAL segments of CRF rats was primarily dependent on PKC activation rather than calcineurin dependent mechanisms.
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PMID:Mechanisms of PKC-dependent Na+ K+ ATPase phosphorylation in the rat kidney with chronic renal failure. 1736 5

Patients with chronic renal failure develop a "uremic" cardiomyopathy characterized by diastolic dysfunction, left ventricular hypertrophy, fibrosis, and systemic oxidant stress. Patients with chronic renal failure also are known to have increases in the circulating concentrations of endogenous cardiotonic steroids (also referred to as endogenous digitalis-like substances.) Endogenous cardiotonic steroids produce reactive oxygen species as part of the signal cascade induced by binding to the plasmalemmal Na/K-ATPase in patients, and this signal cascade appears capable of inducing several key pathophysiologic features of uremic cardiomyopathy. In addition, these patients develop both fibrosis and oxidant stress without a known mechanism. In this review we highlight data supporting the hypothesis that endogenous cardiotonic steroids are a key molecular component involved in the diastolic dysfunction, left ventricular hypertrophy, fibrosis, and systemic oxidant stress associated with chronic kidney disease.
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PMID:Molecular insights into uremic cardiomyopathy: cardiotonic steroids and Na/K ATPase signaling. 1753 29

Vanadium, a trace element, as vanadate (VO4(3-)) is known to interfere with a wide variety of enzymes including Ca2+ ATPase and Na+/+ ATPase. VO4(3-) is excreted mainly via the kidney. In renal insufficiency, the impaired VO4(3-) excretion leads to VO4(3-) accumulation in blood.The present study explored the effect of VO4(3-) on eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared from circulating blood. Stimulators of eryptosis include an increase of the cytosolic Ca2+ concentration. Erythrocyte Ca2+ activity was estimated from Fluo-3 fluorescence, phosphatidylserine exposure from annexin V-binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to VO4(3-) increased cytosolic Ca2+ concentration, enhanced the percentage of annexin V-binding erythrocytes, decreased erythrocyte forward scatter, and lowered the intracellular ATP concentration. In conclusion, VO4(3-) induces eryptosis at least partially through increase of cytosolic Ca2+ concentration, an effect presumably contributing to the development of anemia in chronic renal failure.
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PMID:Vanadate-induced suicidal erythrocyte death. 1831 5

To test the hypothesis that colonic Na(+) transport is altered in the 5/6 nephrectomized rat model of chronic renal failure (CRF), we measured Na(+) fluxes across distal colon from control (CON), CRF, and CRF rats treated with the angiotensin II (ANG II) receptor antagonist losartan (+LOS). We also evaluated overall fluid and Na(+) balance and compared colonic protein and mRNA expression profiles for electroneutral [sodium-hydrogen exchanger (NHE)] and electrogenic Na(+) transport [epithelial sodium channel (ENaC)] in these groups. Consistent with a 60% enhancement in colonic Na(+) absorption in CRF, urinary Na(+) excretion increased by about 50% while serum Na(+) homeostasis was maintained. These CRF-induced changes in Na(+) handling were normalized by treatment with LOS. Net Na(+) absorption was also stimulated in in vitro tissues from CON rats following acute serosal addition of ANG II (10(-7) M), and this increase was blocked by AT(1) antagonism but not by an AT(2) antagonist. In CRF, colonic protein and mRNA expression variably increased for apical NHE2, NHE3, and ENaC alpha-, beta-, gamma-subunits, whereas expression of basolateral NHE1 and Na(+)-K(+)-ATPase (alpha-isoform) remained unaltered. Upregulation of the ENaC subunit mRNA was attenuated somewhat by LOS treatment. Previously, we showed that colonic AT(1) receptor protein is upregulated twofold in CRF, and here we find that AT(1) and AT(2) mRNA and AT(2) protein abundance is unchanged in CRF. We conclude that Na(+) absorption in CRF rat distal colon is increased due to elevated expression of proteins mediating electroneutral and electrogenic uptake and that it is partially mediated by AT(1) receptors.
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PMID:Increased colonic sodium absorption in rats with chronic renal failure is partially mediated by AT1 receptor agonism. 1853 92

We recently demonstrated that the cardiotonic steroid marinobufagenin (MBG) induced fibrosis in rat hearts through direct stimulation of collagen I secretion by cardiac fibroblasts. This stimulation was also responsible for the cardiac fibrosis seen in experimental renal failure. In this study, the effect of MBG on the development of renal fibrosis in rats was investigated. Four weeks of MBG infusion triggered mild periglomerular and peritubular fibrosis in the cortex and the appearance of fibrotic scars in the corticomedullary junction of the kidney. MBG also significantly increased the protein levels and nuclear localization of the transcription factor Snail in the tubular epithelia. It is known that activation of Snail is associated with epithelial-to-mesenchymal transition (EMT) during renal fibrosis. To examine whether MBG alone can trigger EMT, we used the porcine proximal tubular cell line LLC-PK1. MBG (100 nM) caused LLC-PK1 cells grown to confluence to acquire a fibroblast-like shape and have an invasive motility. The expressions of the mesenchymal proteins collagen I, fibronectin, and vimentin were increased twofold. However, the total level of E-cadherin remained unchanged. These alterations in LLC-PK1 cells in the presence of MBG were accompanied by elevated expression and nuclear translocation of Snail. During the time course of EMT, MBG did not have measurable inhibitory effects on the ion pumping activity of its natural ligand, Na(+)-K(+)-ATPase. Our data suggest that the MBG may be an important factor in inducing EMT and, through this mechanism, elevated levels of MBG in chronic renal failure may play a role in the progressive fibrosis.
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PMID:The cardiotonic steroid hormone marinobufagenin induces renal fibrosis: implication of epithelial-to-mesenchymal transition. 1917 1

The Br/+ mutant mouse displays decreased embryological expression of the homeobox transcription factor Six2, resulting in hertitable renal hypoplasia. The purpose of this study was to characterize the renal physiological consequences of embryonic haploinsuffiency of Six2 by analyzing renal morphology and function in the adult Br heterozygous mutant. Adult Br/+ kidneys weighed 50% less than those from wild-type mice and displayed glomerulopathy. Stereological analysis of renal glomeruli showed that Br/+ kidneys had an average of 88% fewer glomeruli than +/+ kidneys, whereas individual glomeruli in Br/+ mice maintained an average volume increase of 180% compared with normal nephrons. Immunostaining revealed increased levels of endothelin-1 (ET-1), endothelin receptors A (ET(A)) and B (ET(B)), and Na-K-ATPase were present in the dilated renal tubules of mutant mice. Physiological features of chronic renal failure (CRF) including elevated mean arterial pressure, increased plasma creatinine, and dilute urine excretion were measured in Br/+ mutant mice. Electron microscopy of the Br/+ glomeruli revealed pathological alterations such as hypercellularity, extracellular matrix accumulation, and a thick irregular glomerular basement membrane. These results indicate that adult Br/+ mice suffer from CRF associated with reduced nephron number and renal hypoplasia, as well as glomerulopathy. Defects are associated with embryological deficiencies of Six2, suggesting that proper levels of this protein during nephrogenesis are critical for normal glomerular development and adult renal function.
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PMID:Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice. 1919 24

The immune-enzyme system of testing was developed to detect the level of Ca2+ ATPase of sarcoplasmic reticulum using monoclonal IgM and IgG antibodies to Ca2+ ATPase. The clinical approbation of the technique was carried out using the sample of 19 patients with acute cardiac infarction Q validated by the increase of content of such common markers of myocardium necrosis as troponin T and creatine phosphokinase MB. The increase of the level of Ca2+ ATPase of sarcoplasmic reticulum was detected in all patients. This occurrence is detected approximately in 4-6 hours after debut and it disappears in 144 hours (6 days). At the same time, Ca2+ ATPase was not detected in 10 Patients with acute traumatic damages of skeleton musculature, in 10 patients with chronic renal failure under hemodialysis and in 20 patients with acute coronary syndrome without rise of ST-segment of cardiogram. These facts testify rather high specificity and sensitivity of the developed technique of detection of the level of Ca2+ ATPase of sarcoplasmic reticulum in blood as biological marker of myocardium necrosis.
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PMID:[The immune-enzyme technique of detection of Ca2+ ATPase of sarcoplasmic reticulum--a new biologic marker of acute cardiac infarction]. 2400 43


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