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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously found that aged rats show decreased proximal acidification without changes in NHE3 or V-H(+) ATPase expression in brush border membrane vesicles. However, we did not identify any mechanism underlying these observations. The aim of the present work was to evaluate some of the regulatory systems of proximal acidification that could be affected by aging. We measured plasma concentrations of parathyroid hormone (PTH) and the amount of cAMP in the renal cortex of young and old Wistar rats. PTH plasma concentration was increased in old rats, whereas, although it showed a tendency to increase, the cAMP content in the renal cortex of old rats was not significantly different compared with the cortex of young rats. We measured the abundance of NHE8 isoforms of the Na(+)/H(+) exchanger in brush border membrane vesicles from proximal convoluted tubules (PCT) of young and old rats by western blot analysis. We performed RT-PCR experiments in renal cortex homogenates from both experimental groups to evaluate mRNA expression of NHE3, NHE8 and H(+)ATPase. In senile rats, we detected a decreased abundance (at both gene expression and protein level) of the NHE8 isoform. These results could explain previous observations in which proximal tubule acidification appears affected in aged rats through a decrease in the activity of ethylisopropyl amiloride (EIPA)- and Bafilomycin-sensitive components, without changes in the NHE3 and V-H(+)ATPase abundance in the apical membrane of the PCT.
...
PMID:Decreased NHE8 isoform expression and defective acidification in proximal convoluted tubules of senile rats. 1923 71

Although deoxycorticosterone acetate (DOCA)-salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA-salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of alpha-1 subunit of Na,K-ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA-salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.
...
PMID:Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA-salt hypertensive rats. 1942 59

Congenital obstructive nephropathy accounts for a major proportion of renal insufficiency in infancy and childhood. In an earlier investigation we demonstrated that bilateral complete ureteral obstruction (BUO) in rats is associated with inadequate urinary acidification [Am J Physiol Renal Physiol. 295(2):F497-506, 2008]. The aim of the study reported here was to determine whether this defect is also associated with unilateral ureteral obstruction (UUO), which is clinically more common than BUO. The time-course of the changes in protein expression levels of major renal acid-base transporters was examined at 7 and 14 weeks in rats with neonatally induced partial unilateral ureteral obstruction (PUUO), which was performed within the first 48 h of life. We observed that protein expression of the renal acid-base transporters NHE3, NBC1, NBCn1, pendrin and Na(+)-K(+)-ATPase was increased in both obstructed and non-obstructed kidneys 7 weeks after the induction of neonatal PUUO. This was confirmed by immunocytochemistry. In contrast, 14 weeks after the induction of PUUO, there was a significant downregulation of the renal acid-base transporters NBC1, NBCn1 and Na(+)-K(+)-ATPase in the obstructed kidneys. These time/age-dependent changes in protein expression were associated with parallel changes in renal function resulting in urine acidification in response to exogenous acid loading. In conclusion, these results show that downregulation of protein expression is a time/age-dependent response to PUUO, which could contribute to the decreased net acid excretion and development of metabolic acidosis in neonatal rats with PUUO.
...
PMID:Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction. 1949 7

Previous studies have shown that over time in culture opossum kidney (OK) cells are endowed with increased Na(+),K(+)-ATPase activity and expression (Silva et al., 2006, J Membr Biol 212:163-175; Silva and Soares-da-Silva, 2007, Am J Physiol Regul Integr Comp Physiol 293:R1764-R1770). The present work evaluated the cytoskeleton reorganization in OK cells at passages 40 and 80 in culture and its possible relationship with membrane transport proteins and cell morphology. It is shown that OK cells with 80 passages in culture have increased size, internal complexity, and total protein expression. In OK cells with 80 passages in culture the use of in-cell western showed that ezrin/radixin/moesin complex was increased by 20%. The most abundant ankyrin-G isoform in OK cells with 40 passages was the approximately 200/220 kDa isoform, whereas in OK cells with 80 passages the most abundant isoform was the approximately 170 kDa isoform. The spectrin-betaII approximately 240 kDa isoform, the predominant isoform in OK cells with 40 passages, was marginally detected in OK cells with 80 passages. Besides Na(+),K(+)-ATPase, GLUT2, and NHE3 expression was also significantly increased in OK cells with 80 passages. It is concluded that the prolonged cell passaging of OK cells results in an interesting and valuable experimental model to analyze the reorganization of the renal cell cytoskeleton proteins and its relationship with transporter and signaling membrane proteins.
...
PMID:Protein cytoskeleton and overexpression of Na(+),K(+)-ATPase in opossum kidney cells. 1958 74

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na(+)/H(+) exchanger isoform 3 (NHE3), Na(+)/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 microg/min for 20 min) that increased PT flow rate approximately 20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng x kg(-1) x min(-1) for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H(+)-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.
...
PMID:Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli. 1986 1

A mathematical model of ascending Henle limb (AHL) epithelium has been fashioned using kinetic representations of Na+-K+-2Cl- cotransporter (NKCC2), KCC4, and type 3 Na+/H+ exchanger (NHE3), with transporter densities selected to yield the reabsorptive Na+ flux expected for rat tubules in vivo. Of necessity, this model predicts fluxes that are higher than those measured in vitro. The kinetics of the NKCC and KCC are such that Na+ reabsorption by the model tubule is responsive to variation in luminal NaCl concentration over the range of 30 to 130 mM, with only minor changes in cell volume. Peritubular KCC accounts for about half the reabsorptive Cl- flux, with the remainder via peritubular Cl- channels. Transcellular Na+ flux is turned off by increasing peritubular KCl, which produces increased cytosolic Cl- and thus inhibits NKCC2 transport. In the presence of physiological concentrations of ammonia, there is a large acid challenge to the cell, due primarily to NH4+ entry via NKCC2, with diffusive NH3 exit to both lumen and peritubular solutions. When NHE3 density is adjusted to compensate this acid challenge, the model predicts luminal membrane proton secretion that is greater than the HCO3(-)-reabsorptive fluxes measured in vitro. The model also predicts luminal membrane ammonia cycling, with uptake via NKCC2 or K+ channel, and secretion either as NH4+ by NHE3 or as diffusive NH3 flux in parallel with a secreted proton. If such luminal ammonia cycling occurs in vivo, it could act in concert with luminal K+ cycling to facilitate AHL Na+ reabsorption via NKCC2. With physiological ammonia, peritubular KCl also blunts NHE3 activity by inhibiting NH4+ uptake on the Na-K-ATPase, and alkalinizing the cell.
...
PMID:A mathematical model of rat ascending Henle limb. II. Epithelial function. 2000 43

Reduced nephron endowment is associated with development of renal and cardiovascular disease. We hypothesized this may be attributable to impaired sodium homoeostasis by the remaining nephrons. The present study investigated whether a nephron deficit, induced by fetal uninephrectomy at 100 days gestation (term=150 days), resulted in (i) altered renal sodium handling both under basal conditions and in response to an acute 0.9% saline load (50 ml.kg-1 of body weight.30 min-1); (ii) hypertension and (iii) altered expression of renal channels/transporters in male sheep at 6 months of age. Uninephrectomized animals had significantly elevated arterial pressure (90.1+/-1.6 compared with 77.8+/-2.9 mmHg; P<0.001), while glomerular filtration rate and renal blood flow (per g of kidney weight) were 30% lower than that of the sham animals. Total kidney weight was similar between the groups. Renal gene expression of apical NHE3 (type 3 Na+/H+ exchanger), ENaC (epithelium Na+ channel) beta and gamma subunits and basolateral Na+/K+ ATPase beta and gamma subunits were significantly elevated in uninephrectomized animals, while ENaC alpha subunit expression was reduced. Urine flow rate and sodium excretion increased in both groups in response to salt loading, but this increase in sodium excretion was delayed by approximately 90 min in the uninephrectomized animals, while total sodium output was 12% in excess of the infused load (P<0.05). In conclusion, the present study shows that animals with a congenital nephron deficit have alterations in tubular sodium channels/transporters and cannot rapidly correct for variations in sodium intake probably contributing to the development of hypertension. This suggests that people born with a nephron deficit should be monitored for early signs of renal and cardiovascular disease.
...
PMID:Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep. 2006 44

Male mice deficient in ESR1 (ERalpha) (Esr1KO mice) are infertile, and sperm recovered from the cauda epididymis exhibit reduced motility and fail to fertilize eggs in vitro. These effects on sperm appear to result from defective epididymal function and not a direct effect on spermatogenesis, as Esr1KO germ cells transplanted into wild-type testes yield normal offspring. We hypothesized that the previously described defect in efferent duct fluid reabsorption would lead to alterations in the epididymal fluid milieu, which would negatively impact sperm function. Analysis of the epididymal fluid revealed that the Esr1KO maintains a higher luminal pH throughout the epididymis, confirming an inability of the efferent ducts and/or epididymis to properly acidify the luminal contents. Subsequent studies showed that these abnormalities were not the result of global defects in epididymal function since protein secretion by the Esr1KO epididymis appeared normal as judged by SDS-PAGE of total secreted proteins and by immunoblotting of candidate secreted proteins. To gain insight into the basis of the aberrant fluid homeostasis in the Esr1KO epididymis, the expression of several enzymes and transporters known to be involved in acid/base regulation were analyzed. The levels of SLC9A3 (NHE3) as well as carbonic anhydrase XIV and SLC4A4 (NBC1) were all reduced in the proximal portion of the Esr1KO epididymis, while other components appeared unaffected, including other ion transporters and ATP6V0A1 (V-ATPase). The altered luminal milieu of the Esr1KO epididymis was shown to lead to a corresponding increase in the intracellular pH of Esr1KO sperm, relative to sperm from control animals. Since pH and bicarbonate ions are critical regulators of sperm cAMP levels and motility, we attempted to bypass the abnormal luminal and intracellular environment by supplementing sperm with exogenous cAMP. This treatment rescued all defective motility parameters, as assayed by CASA, further showing that motility defects are not intrinsic to the sperm but, rather, result from the abnormal epididymal milieu.
...
PMID:Absence of estrogen receptor alpha leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. 2013 Feb 67

The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na(+) excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect of CTS on intracellular protein kinases and Ca(2+) signaling. Significantly, these CTS-provoked signaling events are capable of reducing the surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. These findings suggest that endogenous CTS may play an important role in regulation of tubular Na(+) excretion under physiological conditions; conversely, a defect at either the receptor level (Na/K-ATPase) or receptor-effector coupling would reduce the ability of renal proximal tubular cells to excrete Na(+), thus culminating/resulting in salt-sensitive hypertension.
...
PMID:The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking. 2014 8

Rhesus (Rh) protein involvement in ammonia transport processes in freshwater fish has received considerable attention; however, parallel investigations in seawater species are scant. We exposed pufferfish to high environmental ammonia (HEA; 1 and 5 mmol l(-1) NH(4)HCO(3)) and evaluated the patterns of ammonia excretion and gill Rh mRNA and protein expression. Gill H(+)-ATPase, NHE1, NHE2, NHE3, Na(+)/K(+)-ATPase (NKA), Na(+)/K(+)/2Cl(-) co-transporter (NKCC1) mRNA, H(+)-ATPase activity, NKA protein and activity, were also quantified. Activation of NKA by NH(4)(+) was demonstrated in vitro. The downregulation of Rhbg mRNA and simultaneous upregulations of Rhcg1, H(+)-ATPase, NHE3, NKA, NKCC1 mRNA, H(+)-ATPase activity, and NKA protein and activity levels suggested that during HEA, ammonia excretion was mediated mainly by mitochondria-rich cells (MRCs) driven by NKA with basolateral NH(4)(+) entry via NKA and/or NKCC1, and apical NH(3) extrusion via Rhcg1. Reprotonation of NH(3) by NHE3 and/or H(+)-ATPase would minimise back flux through the Rh channels. Downregulated Rhbg and Rhag mRNA observed in the gill during HEA suggests a coordinated protective response to minimise the influx of external ammonia via the pavement cells and pillar cells, respectively, while routing ammonia excretion through the MRCs. Exposure to hypercapnia (1% CO(2) in air) resulted in downregulated gill and erythrocyte Rhag mRNA. Surprisingly, Rhag, Rhbg, Rhcg1 and Rhcg2 proteins responded to both hypercapnia and HEA with changes in their apparent molecular masses. A dual NH(3)/CO(2) transport function of the pufferfish Rh proteins is therefore suggested. The results support and extend an earlier proposed model of pufferfish gill ammonia excretion that was based on immunolocalisation of the Rh proteins. Passive processes and/or Rhbg and Rhcg2 in the pavement cells may maintain basal levels of plasma ammonia but elevated levels may require active excretion via NKA and Rhcg1 in the MRCs.
...
PMID:Rh glycoprotein expression is modulated in pufferfish (Takifugu rubripes) during high environmental ammonia exposure. 2080 17


<< Previous 1 2 3 4 5 6 7 8 9 10

---