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)

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/tonicity of the renal medullary interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.
...
PMID:Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A. 1720 15

Release of bilateral ureteral obstruction (BUO) is associated with reduced expression of renal aquaporins (AQPs), polyuria, and impairment of urine-concentrating capacity. Recently, we demonstrated that 24 h of BUO is associated with increased cyclooxygenase (COX)-2 expression in the inner medulla (IM) and that selective COX-2 inhibition prevents downregulation of AQP2. In the present study, we tested the hypothesis that COX-2 activity increases in the postobstructive phase and that this increase in COX-2 activity contributes to polyuria and impaired urine-concentrating capacity. We examined the effect of the selective COX-2 inhibitor parecoxib (5 mg.kg(-1).day(-1) via osmotic minipumps) on renal functions and protein abundance of AQP2, AQP3, Na-K-2Cl cotransporter type 2 (NKCC2), and Na-K-ATPase 3 days after release of BUO. At 3 days after release of BUO, rats exhibited polyuria, dehydration and urine and IM tissue osmolality were decreased. There were inverse changes of COX-1 and COX-2 in the IM: COX-2 mRNA, protein, and activity increased, while COX-1 mRNA and protein decreased. Parecoxib reduced urine output 1 day after release of BUO, but sodium excretion and glomerular filtration rate were unchanged. Parecoxib normalized urinary PGE(2) and PGI(2) excretion and attenuated downregulation of AQP2 and AQP3, while phosphorylated AQP2 and NKCC2 remained suppressed. Parecoxib did not improve urine-concentrating capacity in response to 24 h of water deprivation. We conclude that decreased NKCC2 and collapse of the IM osmotic gradient, together with suppressed phosphorylated AQP2, are likely causes for the impaired urine-concentrating capacity and that COX-2 activity is not likely to mediate these changes in the chronic postobstructive phase after ureteral obstruction.
...
PMID:COX-2 activity transiently contributes to increased water and NaCl excretion in the polyuric phase after release of ureteral obstruction. 1722 76

This review focuses on using the knowledge on volume-sensitive transport systems in Ehrlich ascites tumour cells and NIH-3T3 cells to elucidate osmotic regulation of salt transport in epithelia. Using the intestine of the European eel (Anguilla anguilla) (an absorptive epithelium of the type described in the renal cortex thick ascending limb (cTAL)) we have focused on the role of swelling-activated K+- and anion-conductive pathways in response to hypotonicity, and on the role of the apical (luminal) Na+-K+-2Cl- cotransporter (NKCC2) in the response to hypertonicity. The shrinkage-induced activation of NKCC2 involves an interaction between the cytoskeleton and protein phosphorylation events via PKC and myosin light chain kinase (MLCK). Killifish (Fundulus heteroclitus) opercular epithelium is a Cl(-)-secreting epithelium of the type described in exocrine glands, having a CFTR channel on the apical side and the Na+/K+ ATPase, NKCC1 and a K+ channel on the basolateral side. Osmotic control of Cl- secretion across the operculum epithelium includes: (i) hyperosmotic shrinkage activation of NKCC1 via PKC, MLCK, p38, OSR1 and SPAK; (ii) deactivation of NKCC by hypotonic cell swelling and a protein phosphatase, and (iii) a protein tyrosine kinase acting on the focal adhesion kinase (FAK) to set levels of NKCC activity.
...
PMID:The role of volume-sensitive ion transport systems in regulation of epithelial transport. 1728 11

A medullary thick ascending limb (mTAL) cell line, termed raTAL, has been established from freshly isolated rat mTAL tubules and cultured continuously for up to 75 passages; it retains characteristics of mTAL cells even after retrieval from storage in liquid nitrogen for several months. The cells express Tamm-Horsfall glycoprotein (THP), a TAL-specific marker, grow to confluence, exhibit a polygonal morphology characteristic of epithelial cells, and form "domes." Detection of THP, Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), Na(+)-K(+)-ATPase, and renal outer medullary K(+) channel (ROMK) was achieved using indirect immunofluorescence and confocal microscopy. Western blot analysis of NKCC2 expression using two different antibodies revealed a band of approximately 160 kDa, and RT-PCR analysis demonstrated the presence of NKCC2 isoforms A and F, which was confirmed by DNA sequencing; transport of Cl(-) into raTAL cells was inhibited by furosemide. Ouabain- and bumetanide-sensitive oxygen consumption, an index of ion transport activity in the mTAL, was observed in raTAL cells, and the number of domes present was reduced significantly when cells were incubated in the presence of ouabain or bumetanide. The specific activity of Na(+)-K(+)-ATPase activity was determined in raTAL cells (0.67 +/- 0.18 nmol P(i).microg protein(-1).min(-1)), primary cultures of mTAL cells (0.39 +/- 0.08 nmol P(i).microg protein(-1).min(-1)), and freshly isolated mTAL tubules (1.10 +/- 0.29 nmol P(i).microg protein(-1).min(-1)), and approximately 30-50% of total cellular ATPase activity was inhibited by ouabain, in accord with other mTAL preparations. This cell line will be used in studies that address biochemical, molecular, and physiological mechanisms in the mTAL.
...
PMID:Characterization of a long-term rat mTAL cell line. 1767 Aug 98

We investigated whether alpha-lipoic acid (alpha-LA), an antioxidant, attenuates the ischemia-reperfusion (I/R)-induced dysregulation of these transporters. Both renal pedicles of male Sprague-Dawley rats were clamped for 40 min. alpha-LA (80 mg/kg) was administered intraperitoneally before and immediately after induction of ischemia. After 2 days, the expression of aquaporins (AQPs), sodium transporters, and nitric oxide synthases (NOS) was determined in the kidney by immunoblotting and immunohistochemistry. The expression of endothelin-1 (ET-1) mRNA was determined by real-time PCR. Activities of adenylyl cyclase and guanylyl cyclase were measured by stimulated generation of cAMP and cGMP, respectively. The expression of AQP1-3 as well as that of the alpha(1)-subunit of Na-K-ATPase, type 3 Na/H exchanger, Na-K-2Cl cotransporter, and Na-Cl cotransporter was markedly decreased in response to I/R. The expression of type VI adenylyl cyclase was decreased in I/R-injured rats, which was counteracted by the treatment of alpha-LA. AVP-stimulated cAMP generation was blunted in I/R rats and was then ameliorated by alpha-LA treatment. alpha-LA treatment attenuated the downregulation of AQPs and sodium transporters. The expression of endothelial NOS was decreased in I/R rats, which was prevented by alpha-LA. The cGMP generation in response to sodium nitroprusside was blunted in I/R rats, which was also significantly prevented by alpha-LA. The mRNA expression of ET-1 was increased, which was recovered to the control level by alpha-LA treatment. In conclusion, alpha-LA treatment prevents I/R-induced dysregulation of AQPs and sodium transporters in the kidney, possibly through preserving normal activities of local AVP/cAMP, nitric oxide/cGMP, and ET systems.
...
PMID:Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats. 1803 50

Tubuloglomerular feedback (TGF) describes a causal and direct relationship between tubular NaCl concentration at the end of the ascending limb of the loop of Henle and afferent arteriolar tone. The use of genetically altered mice has led to an expansion of our understanding of the mechanisms underlying the functional coupling of epithelial, mesangial, and vascular cells in TGF. Studies in mice with deletions of the A or B isoform of NKCC2 (Na,K,2Cl cotransporter) and of ROMK indicate that NaCl uptake is required for response initiation. A role for transcellular salt transport is suggested by the inhibitory effect of ouabain in mutant mice with an ouabain-sensitive alpha1 Na,K-ATPase. No effect on TGF was observed in NHE2- and H/K-ATPase-deficient mice. TGF responses are abolished in A1 adenosine receptor-deficient mice, and studies in mice with null mutations in NTPDase1 or ecto-5'-nucleotidase indicate that adenosine involved in TGF is mainly derived from dephosphorylation of released ATP. Angiotensin II is a required cofactor for the elicitation of TGF responses, as AT1 receptor or angiotensin-converting enzyme deficiencies reduce TGF responses, mostly by reducing adenosine effectiveness. Overall, the evidence from these studies in genetically altered mice indicates that transcellular NaCl transport induces the generation of adenosine that, in conjunction with angiotensin II, elicits afferent arteriolar constriction.
...
PMID:Tubuloglomerular feedback: mechanistic insights from gene-manipulated mice. 1841 52

Urinary tract obstruction impairs renal function and is often associated with a urinary acidification defect caused by diminished net H+ secretion and/or HCO3- reabsorption. To identify the molecular mechanisms of these defects, protein expression of key acid-base transporters were examined along the renal nephron and collecting duct of kidneys from rats subjected to 24-h bilateral ureteral obstruction (BUO), 4 days after release of BUO (BUO-R), or BUO-R rats with experimentally induced metabolic acidosis (BUO-A). Semiquantitative immunoblotting revealed that BUO caused a significant reduction in the expression of the type 3 Na+/H+ exchanger (NHE3) in the cortex (21 +/- 4%), electrogenic Na+/HCO3- cotransporter (NBC1; 71 +/- 5%), type 1 bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC2; 3 +/- 1%), electroneutral Na+/HCO3- cotransporter (NBCn1; 46 +/- 7%), and anion exchanger (pendrin; 87 +/- 2%). The expression of H+-ATPase increased in the inner medullary collecting duct (152 +/- 13%). These changes were confirmed by immunocytochemistry. In BUO-R rats, there was a persistent downregulation of all the acid-base transporters including H+-ATPase. Two days of NH4Cl loading reduced plasma pH and HCO3- levels in BUO-A rats. The results demonstrate that the expression of multiple renal acid-base transporters are markedly altered in response to BUO, which may be responsible for development of metabolic acidosis and contribute to the urinary acidification defect after release of the obstruction.
...
PMID:Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney. 1850 79

During high-salt (HS) diet the kidney increases urinary Na+ and volume excretion to match intake. We recently reported that HS provokes a redistribution of distal convoluted tubule Na+-Cl- cotransporter (NCC) from apical to subapical vesicles and decreases NCC abundance. This study aimed to test the hypothesis that the other renal Na+ transporters' abundance and or subcellular distribution is decreased by HS diet. Six-week-old Sprague-Dawley rats were fed a normal (NS) 0.4% NaCl diet or a HS 4% NaCl diet for 3 wk or overnight. Kidneys excised from anesthetized rats were fractionated on density gradients or analyzed by microscopy; transporters and associated regulators were detected with specific antibodies. Three-week HS doubled Na+/H+ exchanger (NHE)3 phosphorylation at serine 552 and provoked a redistribution of NHE3, dipeptidyl peptidase IV (DPPIV), myosin VI, Na+-Pi cotransporter (NaPi)-2, ANG II type 2 receptor (AT2R), aminopeptidase N (APN), Na+-K+-2Cl- cotransporter (NKCC2), epithelial Na+ channel (ENaC) beta-subunit, and Na+-K+-ATPase (NKA) alpha1- and beta1-subunits from low-density plasma membrane-enriched fractions to higher-density intracellular membrane-enriched fractions. NHE3, myosin VI, and AT2R retraction to the base of the microvilli (MV) during HS was evident by confocal microscopy. HS did not change abundance of NHE3, NKCC, or NKA alpha1- or beta1-subunits but increased ENaC-beta in high-density intracellular enriched membranes. Responses to HS were fully apparent after just 18 h. We propose that retraction of NHE3 to the base of the MV, driven by myosin VI and NHE3 phosphorylation and accompanied by redistribution of the NHE3 regulator DPPIV, contributes to a decrease in proximal tubule Na+ reabsorption during HS and that redistribution of transporters out of low-density plasma membrane-enriched fractions in the thick ascending limb of the loop of Henle and distal nephron may also contribute to the homeostatic natriuretic response to HS diet.
...
PMID:Effects of dietary salt on renal Na+ transporter subcellular distribution, abundance, and phosphorylation status. 1865 79

Studies from this and other laboratories have shown that the Na-K-2Cl cotransporter is present in BBB endothelial cells is stimulated by factors present during cerebral ischemia. Further, our in situ studies have shown that the cotransporter resides predominantly in the luminal BBB membrane. This is consistent with the hypothesis that a luminal cotransporter works with abluminal Na/K ATPase to secrete NaCl into the brain, and during stroke, BBB cotransporter activity is increased such that the barrier hypersecretes NaCl and water into the brain, facilitating cytotoxic edema formation. Our in vivo MCAO stroke studies provide further support for a role of the BBB cotransporter in cerebral ede-ma formation. Collectively, these findings suggest that the BBB Na-K-2Cl cotransporter does indeed substantially contribute to cerebral edema formation in stroke.
...
PMID:The role of the blood-brain barrier Na-K-2Cl cotransporter in stroke. 1872 28

Prenatally programmed hypertension induced by maternal protein restriction is associated with increased expression of the renal tubular Na+/K+/2Cl- co-transporter (NKCC2) and the Na+/Cl- co-transporter (NCC). This has led to the suggestion that renal Na+ retention contributes to the development of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero). However, this hypothesis has not been tested in vivo. Renal clearance measurements in hypertensive 4-week-old male and female LP rats showed that, although the glomerular filtration rate remained unaltered, urine flow (P<0.01) and urinary Na+ excretion rates (1.6+/-0.3 and 3.0+/-0.4 mumol.min-1.100 g-1 of body weight in control male and LP male respectively; P<0.001) were increased. Na+ excretion was positively correlated with mean arterial pressure in both males (P<0.01) and females (P<0.05), but neither the slope nor the intercept differed between control and LP rats. Fractional excretion of Na+ was increased in male (1.5+/-0.2 and 3.0+/-0.5% in control and LP rats respectively; P<0.001) and female LP rats, implying reduced tubular reabsorption of Na+. Western blotting and quantitative PCR showed that NKCC2 expression was increased, whereas NCC mRNA was not up-regulated. Na+/K+ ATPase alpha1 subunit expression did not differ from controls; however, there was a significant reduction in whole kidney pump activity (23.4+/-1.8 and 17.7+/-1.2 nmol of phosphate.mug-1 of protein.h-1 in control male and male LP rats respectively; P<0.001); immunohistochemistry showed that the alpha1 subunit was virtually absent from the inner medulla. The greater Na+ excretion of LP rats can be explained, in part, by a pressure-natriuresis mechanism; however, the loss of the Na+/K+ ATPase alpha1 subunit from the inner medulla and up-regulation of NKCC2 suggests that altered renal Na+ handling is also programmed prenatally.
...
PMID:Prenatal programming of renal sodium handling in the rat. 1912 40


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

---