UNIPROT:P41181 - FACTA Search

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Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In distal renal tubular acidosis (dRTA) the tubular secretion of hydrogen ion in the distal nephron is impaired, leading to the development of metabolic acidosis, frequently accompanied by hypokalemia, nephrocalcinosis, and metabolic bone disease. The condition can be familial, when it is usually inherited as an autosomal dominant, though there is a rarer autosomal recessive form associated with nerve deafness. It has been shown that the autosomal dominant form of dRTA is associated with a defect in the anion exchanger (AE1) of the renal collecting duct intercalated cell. This transporter is a product of the same gene (AE1) as the erythrocyte anion exchanger, band 3. In this review we will look at the evidence for this association. Studies of genomic DNA from families with this disorder have shown, both by genetic linkage studies and by DNA sequencing, that affected individuals are heterozygous for mutations in the AE1 gene whilst unaffected family members have a normal band 3 sequence. Mutations have been found in the region of proposed helices 6 and 7 of the membrane domain of band 3 and involve amino acids Arg-589 and Ser-613, and in the COOH-terminal domain of band 3. Studies of red cell band 3 from these families have provided information on the effect these mutations have on the structure and function of erythrocyte band 3. Expression studies of the erythroid and kidney isoforms of the mutant AE1 proteins, in Xenopus laevis oocytes, have shown that they retained chloride transport activity, suggesting that the disease in the dRTA families is not related simply to the anion transport activity of the mutated proteins. A possible explanation for the dominant effect of these mutant AE1 proteins in the kidney cell is that these mutations affect the targeting of AE1 from the basolateral to the apical membrane of the alpha-intercalated cell.
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PMID:The association between familial distal renal tubular acidosis and mutations in the red cell anion exchanger (band 3, AE1) gene. 1035 4

The renal inner medulla is characterised by elevated extracellular concentrations of NaCl, urea, potassium and hydrogen ions, an environment that may affect cell viability negatively. High amounts of HSP72, a stress protein allowing cells to resist harmful situations, are also observed in this region. The present study examined HSP72 induction by various medullary stress factors, individually or in combination, in MDCK cells, a renal epithelial cell line expressing characteristics of the medullary collecting duct. MDCK cells were incubated for 3 days in media containing elevated concentrations of NaCl, urea, potassium and hydrogen ions individually or in combination. HSP72 mRNA and protein expression were determined by Northern and Western blot analyses, respectively. HSP72 expression was enhanced moderately by addition of 50 mM NaCl to normal medium at pH 7.4 but enhanced strongly when added at pH 6.5. The latter degree of HSP72 induction was comparable to that observed when 150 mM NaCl was added at pH 7.4. In normal medium (pH 7.4) containing 300 mM urea, MDCK HSP72 expression was not different from controls. In contrast, urea-induced HSP72 expression was clearly evident when medium pH was lowered to 6.5. Potassium at 20 or 40 mM induced HSP72 only slightly. These results indicate that expression of HSP72 in renal epithelial cells is regulated synergistically by NaCl, urea and pH. Since HSP72 is only slightly induced by increased potassium, this probably reflects the changes in medium osmolality rather than a specific effect of potassium. The high medullary HSP72 content observed even in diuresis may be due to co-operative effects of medullary solutes on HSP72 expression.
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PMID:Influence of NaCl, urea, potassium and pH on HSP72 expression in MDCK cells. 1065 Oct 17

Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l) increase in the plasma HCO(3-) concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3 mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14+/-12 mmol; not significant). The plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/-1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+) excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH(3) production) and by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH(3) production is insufficient to obligate an increase in net acid excretion.
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PMID:On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl. 1088 57

A mathematical model of the outer medullary collecting duct (OMCD) has been developed, consisting of alpha-intercalated cells and a paracellular pathway, and which includes Na(+), K(+), Cl(-), HCO(3)(-), CO(2), H(2)CO(3), phosphate, ammonia, and urea. Proton secretion across the luminal cell membrane is mediated by both H(+)-ATPase and H-K-ATPase, with fluxes through the H-K-ATPase given by a previously developed kinetic model (Weinstein AM. Am J Physiol Renal Physiol 274: F856-F867, 1998). The flux across each ATPase is substantial, and variation in abundance of either pump can be used to control OMCD proton secretion. In comparison with the H(+)-ATPase, flux through the H-K-ATPase is relatively insensitive to changes in lumen pH, so as luminal acidification proceeds, proton secretion shifts toward this pathway. Peritubular HCO(3)(-) exit is via a conductive pathway and via the Cl(-)/HCO(3)(-) exchanger, AE1. To represent AE1, a kinetic model has been developed based on transport studies obtained at 38 degrees C in red blood cells. (Gasbjerg PK, Knauf PA, and Brahm J. J Gen Physiol 108: 565-575, 1996; Knauf PA, Gasbjerg PK, and Brahm J. J Gen Physiol 108: 577-589, 1996). Model calculations indicate that if all of the chloride entry via AE1 recycles across a peritubular chloride channel and if this channel is anything other than highly selective for chloride, then it should conduct a substantial fraction of the bicarbonate exit. Since both luminal membrane proton pumps are sensitive to small changes in cytosolic pH, variation in density of either AE1 or peritubular anion conductance can modulate OMCD proton secretory rate. With respect to the OMCD in situ, available buffer is predicted to be abundant, including delivered HCO(3)(-) and HPO(4)(2-), as well as peritubular NH(3). Thus, buffer availability is unlikely to exert a regulatory role in total proton secretion by this tubule segment.
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PMID:A mathematical model of the outer medullary collecting duct of the rat. 1089 85

Renal apical chloride-base exchangers are essential to electrolyte and acid-base homeostasis. Different functional isoforms of apical anion exchangers have been identified in kidney proximal tubule and cortical collecting duct. Included amongst these are the following: chloride-formate, chloride-oxalate, and chloride-hydroxyl exchangers in proximal tubule; and chloride-bicarbonate exchanger in cortical collecting duct. Chloride-formate exchange, which was first identified in kidney proximal tubule, works in parallel with the apical sodium-hydrogen exchanger, and is thought to reabsorb the bulk of luminal chloride. Despite numerous studies, the molecular identities of apical chloride-base exchangers have remained unknown. Recent studies have identified a new class of anion exchangers, including pendrin (encoded by the PDS gene) and downregulated in adenoma (DRA, encoded by the DRA gene). Pendrin is expressed in the kidney, whereas DRA is not. Functional studies indicate that pendrin can function in chloride-formate and chloride-base exchange modes. It is unlikely that pendrin is the apical chloride-formate exchanger in the kidney proximal tubule. However, it is the only molecule that has been shown to mediate chloride-formate exchange. In the present review, recent studies regarding the renal distribution and membrane localization of pendrin, and its functional properties, including its roles in chloride reabsorption and base excretion, are addressed.
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PMID:Molecular physiology of the renal chloride-formate exchanger. 1149 64

Sodium-hydrogen exchanger regulatory factor-1 and -2 (NHERF-1 and NHERF-2) are adaptor proteins that regulate renal electrolyte transport and interact with the platelet-derived growth factor receptors (PDGFR). The distribution of the NHERF proteins and PDGFR was studied in normal human kidneys and in renal transplant rejection using immunocytochemistry. In normal kidneys, NHERF-1 was detected in proximal tubules. NHERF-2 was detected in glomeruli, peritubular capillaries, and collecting duct principal cells. NHERF-2 was also weakly detected in the proximal tubule. PDGFR-beta was detected in glomeruli but not in tubules while PDGFR-alpha was detected in renal tubules and minimally in glomeruli. Acute and chronic transplant rejection was associated with increased expression of PDGFR-alpha in tubules and expression in the glomeruli. PDGFR-beta expression in the glomeruli was increased in transplant rejection and became detectable in tubules. Expression of NHERF-1 and NHERF-2 was not different in the patient groups. These results indicate that in contrast to the rat, both NHERF isoforms are detected in the human proximal tubule. In renal transplant rejection, there is increased expression of both PDGFR subtypes consistent with a role for PDGF in injury or repair.
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PMID:Expression of NHERF-1, NHERF-2, PDGFR-alpha, and PDGFR-beta in normal human kidneys and in renal transplant rejection. 1286 27

We identified the inv gene that encodes left and right asymmetry and regulates kidney development based on the information of the inv mutant mouse. However, functional properties and the modulator of gene expression of inv have been unclear. We used the tissue injury model for assessing the functional roles of inv in ischemia reperfusion injury (IRI). The kidney tissue taken from rats with IRI showed reciprocal changes in mRNA expression of inv: a 0.25-fold decrease at 6 hours and then a gradual increase to a maximum 1.8-fold rise at 10 days of reperfusion. Next, oxidative stress was induced by exposing mouse inner medullary collecting duct (mIMCD-3) cells to hydrogen peroxide(H2O2) in the medium. Real-time PCR showed that mRNA expression of inv decreased 0.52-fold at 3 hours with 0.2 mM H2O2 in the medium, and then increased 3.1-fold at 24 hours with 0.1 mM H2O2 in the medium. RNA interference (RNAi) is a powerful tool to inhibit gene expression in experimental model systems. We knocked down inv gene expression in mIMCD-3 cells using RNAi to investigate the function of the inv gene. We designed a small interfering RNA (siRNA) to target the coding region of inv (inv-siRNA) and random-sequence scrambled siRNA(control siRNA). mIMCD-3 cells transfected with either the inv-siRNA or control siRNA were observed by microscopy. The cells transfected with inv-siRNA progressively lost cell-to-cell contact and the cell population significantly diminished approximately 48 hours post-transfection. The changes in gene expression profile were observed at time points (36 hours) using real-time PCR-based gene screening with categorized primer sets. Several genes related to structural protein of the matrix were downregulated. In contrast, repairing related genes were upregulated. In conclusion, gene expression of inv was modulated under oxidative stress and the inv gene may play a role in repairing and regenerating renal epithelial cells.
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PMID:[Functional analysis of the left-right determinant inv (inversion of embryonic turning) gene]. 1557 Aug 95

Metabolic alkalosis is a common feature of hypokalemic hypertensive syndromes associated with angiotensin II excess. The alkalosis-generating effect of angiotensin II is usually ascribed to its stimulatory effect on aldosterone secretion, a hormone that upregulates collecting duct hydrogen ion secretion. We studied the effect of angiotensin II infusions on the expression of B1 and a4 protein, subunits of the renal H+-ATPase in adrenalectomized rats. Adrenalectomized rats were given either angiotensin II or vehicle for 7 days via osmotic mini-pumps. H+-ATPase B1 protein expression was evaluated by Western blot analysis in isolated medulla and cortex plasma membrane preparations from one kidney, whereas the contralateral kidney was used for immunostaining. By Western blotting, the relative abundance of B1 protein was 2-fold higher in renal medulla membranes from rats with intact adrenal glands (sham surgery) than from adrenalectomized rats (219+/-47%, n=12; P<0.05). In contrast to renal medulla, adrenalectomy did not significantly alter the relative abundance of B1 protein in renal cortex. Angiotensin II also did not significantly alter the relative levels of B1 protein in the cortex, but it increased it significantly in renal medullary membranes (231+/-56%, n=8; P<0.005). Moreover, enhanced H+-ATPase B1 subunit protein immunoreactivity was found in medullary collecting duct segments of rats infused with angiotensin II. In contrast to B1, expression of a4, another subunit of the H+-ATPase was not altered by adrenalectomy or angiotensin II. We conclude that adrenalectomy decreases whereas angiotensin II increases H+-ATPase B1 subunit expression in medullary, but not in cortical collecting ducts. By increasing the relative abundance of the B1 subunit of H+-ATPase in the collecting duct, angiotensin II excess may lead to increased hydrogen ion secretion and thus metabolic alkalosis-a common feature of hypertensive syndromes associated with angiotensin II overactivity.
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PMID:Angiotensin II increases H+-ATPase B1 subunit expression in medullary collecting ducts. 1569 54

Recent data have implicated nuclear factor-kappaB (NF-kappaB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-kappaB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-kappaBalpha (I-kappaBalpha) and Bcl-2. Overexpression of I-kappaBalpha and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-kappaBalpha significantly decreased H2O2-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-kappaBalpha, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-kappaBalpha overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-kappaB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-kappaB mediates H2O2-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.
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PMID:Roles of NF-kappaB and bcl-2 in two differential modes of cell death of mouse cortical collecting duct cells. 1574 59

Molecular and pathogenetic mechanisms in sodium retention and water reabsorption of nephrotic edema are discussed. Are reported and analyzed molecular mechanisms about sodium retention in collecting duct cells regarding activation and surface expression of epithelial sodium channels (ENaC) and sodium-potassium-ATPase (Na,K-ATPase) by aldosterone, vasopressin, natriuretic peptide system (underfill theory): is necessary a better understanding about the dysregulation of ENaC and Na,K-ATPase surface expression and the resistance to natriuretic peptide system. Are also reported and analyzed molecular mechanisms of sodium retention in proximal tubule cells regarding intrinsic albumin toxicity upon type 3 sodium-hydrogen exchanger ionic pump and the activity of sodium-hydrogen exchanger regulatory factor protein (overfill theory): a better knowledge about the link between albumin, sodium-hydrogen exchanger type 3 (NHE3) ionic pump, sodium-hydrogen exchanger regulatory factor protein is necessary. Then molecular mechanisms of vasopressin free water retention through acquaporin water channels in collecting duct cells are discussed: further studies are necessary to understand vasopressin release pathway (osmotic/nonosmotic) and V2 receptor activation with cell surface expression of renal acquaporins water channel.
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PMID:Molecular pathogenetic mechanisms of nephrotic edema: progress in understanding. 1589 43

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