Abstract:
BACKGROUND:Tubular transepithelial reabsorption of chloride along the nephron is a major determinant of body salt and water homeostasis and blood pressure regulation. About 40% of the glomerulary filtered sodium chloride are reabsorbed in the distal nephrons. Vectorial transepithelial sodium chloride transport is critically dependent on the function of basolateral ClC-K type chloride channels there. Modulation of ClC-Kb chloride channel activity by polymorphic variations of the CLCNKB gene, thus, could form a molecular basis for salt sensitivity of blood pressure regulation. In this study we tested the effect of several polymorphic variants on ClC-Kb chloride channel activity. METHODS:After heterologous expression in Xenopus oocytes, ClC-Kb channel activity and surface expression in presence of the ClC-K beta subunit barttin were determined by two-electrode voltage-clamp analysis, immunofluorescence, and ClC-Kb surface enzyme-linked immunosorbent assay (ELISA). RESULTS:Chloride currents induced by the ClC-Kb variants L27R, G214A, I419V, T562M, and E578K were not significantly different from wild-type currents. The ClC-KbT481S variation, however, which showed a frequency of 20% in our control population, dramatically activated chloride conductance by a factor of 20. Activation of chloride currents was also observed after introducing homologous mutations in ClC-Ka and ClC-K1, but not in ClC-2 and ClC-5 chloride channels. ClC-Kb activation by the T481S mutation did not change intrinsic ion channel pore properties and did not require increased surface expression of ClC-KbT481S. CONCLUSION:Genetic heterogeneity of ClC-Kb chloride channels correlates with functional heterogeneity, which assigns ClC-Kb to a set of genes potentially relevant for polygenic salt-sensitivity of blood pressure regulation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Jeck N,Waldegger P,Doroszewicz J,Seyberth H,Waldegger Sdoi
10.1111/j.1523-1755.2004.00363.xsubject
Has Abstractpub_date
2004-01-01 00:00:00pages
190-7issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49690-5journal_volume
65pub_type
杂志文章abstract:BACKGROUND:In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen result in progressive renal failure. This nephropathy appears to relate to the arrest of a switch from an alpha 1/alpha 2 to an alpha 3/alpha 4/alpha 5 network of type IV collagen in the developing glomer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00188.x
更新日期:1998-12-01 00:00:00
abstract::Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a sm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.188
更新日期:1992-05-01 00:00:00
abstract::Daily calcitriol therapy has been reported to improve linear growth in children with renal bone disease, and 1,25-dihydroxyvitamin D is a key regultor of chondrocyte proliferation and differentiation. Whereas large intermittent doses of calcitriol can lower serum parathyroid hormone (PTH) levels and reverse the skelet...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00724.x
更新日期:1998-01-01 00:00:00
abstract::Our previous in vivo study demonstrated that methylprednisolone (MP) activates glomerular antioxidant enzymes and attenuates glomerular oxidant injuries, including those in experimental nephrosis. The present study investigates the cellular mechanism of the MP-induced activation of antioxidant enzymes and their contri...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.25
更新日期:1994-01-01 00:00:00
abstract:BACKGROUND:Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism. METHODS:Parathyroid glands from 19 patients with primary (1 deg...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00863.x
更新日期:2000-02-01 00:00:00
abstract::The ankyrin repeat and sterile α motif (SAM) domain-containing six gene (Anks6) is a candidate for polycystic kidney disease (PKD). Originally identified in the PKD/Mhm(cy/+) rat model of PKD, the disease is caused by a mutation (R823W) in the SAM domain of the encoded protein. Recent studies support the etiological r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.122
更新日期:2015-08-01 00:00:00
abstract::Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001757
更新日期:2006-10-01 00:00:00
abstract::Simple life-table analyses have not identified the reasons for the steady improvement over the years in graft survival. The use of more sophisticated multifactorial statistical techniques is indicated to identify prognostic factors and to explore the "center effect" on graft survival. An agenda for retrospective analy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.188
更新日期:1983-10-01 00:00:00
abstract::Macrophages are inflammatory cells with important roles in the propagation of renal injury. More recently they have also been shown to be important in the resolution of inflammation. Wang et al. show that macrophages can be modulated ex vivo by cytokine stimulation, localize to renal tissue, and slow progression of ex...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002332
更新日期:2007-08-01 00:00:00
abstract::Genetic deletion of the adenosine A1 receptor (A1AR) increased renal injury following ischemia-reperfusion injury suggesting that receptor activation is protective in vivo. Here we tested this hypothesis by expressing the human-A(1)AR in A(1)AR knockout mice. Renal ischemia-reperfusion was induced in knockout mice 2 d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.699
更新日期:2009-04-01 00:00:00
abstract::Enalapril effectively decreases hematocrits in patients with postrenal transplant erythrocytosis (PTE). We studied the effect of enalapril withdrawal on erythropoiesis in 18 patients with PTE who had been treated for 13 +/- 8 months. Hematocrit, reticulocyte count, plasma erythropoietin, and plasma insulin-like growth...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.411
更新日期:1994-11-01 00:00:00
abstract::Substantial evidence implicates impaired renal excretion of sodium as the major culprit in the pathogenesis of hypertension. The key question is: How does the impairment of Na+ excretion lead to increased peripheral vascular resistance and elevation of the blood pressure? Here we describe the evidence that elevated le...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.260
更新日期:1996-06-01 00:00:00
abstract::Monocyte chemoattractant protein 1 (MCP-1) is a C-C chemokine with potent monocyte chemotactic and activating properties that may contribute to glomerular macrophage infiltration in anti-GBM Ab GN. We have previously reported increased glomerular steady state expression of MCP-1 mRNA relative to GAPDH mRNA in the hete...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.363
更新日期:1996-08-01 00:00:00
abstract::The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.178
更新日期:1993-06-01 00:00:00
abstract:BACKGROUND:The aim of this study was to establish whether there is a differential effect of mode of dialysis, hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) on the dyslipidemia of renal failure. METHODS:The lipoprotein profile was determined in 61 non-diabetic patients on chronic HD (N = 30) an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00375.x
更新日期:1999-04-01 00:00:00
abstract::VLDL receptor (VLDL-R) is a novel member of the LDL receptor gene family with distinct tissue distribution and function. It binds and internalizes VLDL particles and is primarily expressed in skeletal muscle, heart, brain and adipose tissue, which use fatty acids for energy production or storage. CRF is associated wit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.129
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Nitric oxide inactivation by superoxide impairs endothelium-dependent vasodilation and plays a role in various forms of hypertension. Almost no data exist regarding hypertension secondary to chronic renal failure. Previous studies have shown that endothelium-related relaxations, secondary to decreased nitric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00166.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS:Detailed clinical ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1523-1755.2000.00989.x
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:During inflammation, polymorphonuclear neutrophils (PMNs) migrate into the affected tissue interacting with extracellular matrix (ECM) proteins. We tested the hypothesis that PMN-matrix interaction affects PMN apoptosis. METHODS:Apoptosis of human PMNs was detected by DNA-fragmentation assay and was quantit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00280.x
更新日期:1999-02-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract::It has been shown that somatostatin inhibits the antidiuretic action of vasopressin in toad urinary bladder in vitro and in dogs and rats in vivo. The presence of somatostatin-like immunoreactivity (SLI) in the urinary bladder and kidney of the toad has suggested the possibility that somatostatin may act as a local pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.223
更新日期:1983-12-01 00:00:00
abstract::The metabolism of phenylalanine and tyrosine was evaluated in six normal men, five chronically uremic men, and three men undergoing maintenance hemodialysis. Phenylalanine, tyrosine, and 13 acidic metabolites of those amino acids were measured in plasma postabsorptively and in plasma and urine after a phenylalanine lo...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1978.104
更新日期:1978-08-01 00:00:00
abstract:BACKGROUND:Chronic inflammation and oxidative stress are highly prevalent in patients with chronic kidney disease and end-stage renal disease (ESRD). These conditions contribute to high mortality rates associated with cardiovascular disease, the leading cause of death in this patient population. To our knowledge, no pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00656.x
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintag...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00945.x
更新日期:2000-03-01 00:00:00
abstract::The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient. Hypercalcemia (5.48 +/- 0.03 mEq/liter in high PTH animals, 4...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.68
更新日期:1982-04-01 00:00:00
abstract:BACKGROUND:Normalization of proteinuria and even regression of glomerulosclerosis seem to occur in progressive renal disease upon blockade of the renin-angiotensin system. Here we quantified the effect of a combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00526.x
更新日期:2002-09-01 00:00:00
abstract::Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of B...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.161
更新日期:2008-07-01 00:00:00
abstract::Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.482
更新日期:2013-06-01 00:00:00
abstract::Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001966
更新日期:2006-12-01 00:00:00
abstract::We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuE...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2011.349
更新日期:2012-02-01 00:00:00