The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system.; ; et al in Pflügers Archiv : European Journal of Physiology (2011), 462 Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5 ... [more ▼] Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts. [less ▲] Detailed reference viewed: 14 (3 ULg) Decreased renal accumulation of aminoglycoside reflects defective receptor-mediated endocytosis in cystic fibrosis and Dent's disease.; ; et al in Pflügers Archiv : European Journal of Physiology (2011), 462(6), 851-60 The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance ... [more ▼] The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance of AG is enhanced in cystic fibrosis (CF) patients, which might reflect the role of CFTR in PT cell endocytosis. In order to assess the role of chloride transporters on the renal handling of AG, we investigated gentamicin uptake and renal accumulation in mice lacking functional CFTR (Cftr ( F/F)) or knock-out for the Cl(-)/H(+) exchanger ClC-5 (Clcn5 ( Y/- )). The latter represent a paradigm of PT dysfunction and defective receptor-mediated endocytosis. As compared with controls, Cftr ( F/F) and Clcn5 ( Y/- ) mice showed a 15% to 85% decrease in gentamicin accumulation in the kidney, respectively, in absence of renal failure. Studies on primary cultures of Cftr ( F/F) and Clcn5 ( Y/- ) mouse PT cells confirmed the reduction in gentamicin uptake, although colocalization with endosomes and lysosomes was maintained. Quantification of endocytosis in PT cells revealed that gentamicin, similar to albumin, preferentially binds to megalin. The functional loss of ClC-5 or CFTR was reflected by a decrease of the endocytic uptake of gentamicin, with a more pronounced effect in cells lacking ClC-5. These results support the concept that CFTR, as well as ClC-5, plays a relevant role in PT cell endocytosis. They also demonstrate that the functional loss of these two chloride transporters is associated with impaired uptake of AG in PT cells, reflected by a decreased renal accumulation of the drug. [less ▲] Detailed reference viewed: 8 (0 ULg) CFTR and defective endocytosis: new insights in the renal phenotype of cystic fibrosis.JOURET, François ; in Pflügers Archiv : European Journal of Physiology (2009), 457(6), 1227-36 Inactivation of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis (CF). Although CFTR is expressed in the kidney, no overwhelming renal phenotype is ... [more ▼] Inactivation of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis (CF). Although CFTR is expressed in the kidney, no overwhelming renal phenotype is associated with CF. Recent studies have shown that the level of CFTR mRNA in mouse kidney approaches that found in lung. CFTR is particularly abundant in the apical area of proximal tubule cells, where it co-distributes with the Cl(-)/H(+) exchanger ClC-5 and Rab5a in endosomes. The biological relevance of CFTR in proximal tubule endocytosis has been tested in CF mouse models and CF patients. Mice lacking CFTR show a defective receptor-mediated endocytosis, as evidenced by impaired uptake of (125)I-beta(2)-microglobulin, a decreased expression of the cubilin receptor in the kidney, and a significant excretion of cubilin and its low-molecular-weight ligands into the urine. Low-molecular-weight proteinuria (and particularly transferrinuria) is similarly detected in CF patients in comparison with normal controls or patients with chronic lung inflammation. These studies suggest that the functional loss of CFTR impairs the handling of low-molecular-weight proteins by the kidney, supporting a role of CFTR in receptor-mediated endocytosis in proximal tubule cells. The selective proteinuria should be integrated in the pathophysiology of multi-systemic complications increasingly observed in CF patients. [less ▲] Detailed reference viewed: 12 (0 ULg) Phosphoinositide phosphatases in a network of signaling reactions; ; Schurmans, Stéphane et alin Pflügers Archiv : European Journal of Physiology (2007), 455 Phosphoinositide phosphatases dephosphorylate the three positions (D-3, 4 and 5) of the inositol ring of the poly-phosphoinositides. They belong to different families of enzymes. The PtdIns(3,4)P(2) 4 ... [more ▼] Phosphoinositide phosphatases dephosphorylate the three positions (D-3, 4 and 5) of the inositol ring of the poly-phosphoinositides. They belong to different families of enzymes. The PtdIns(3,4)P(2) 4-phosphatase family, the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN), SAC1 domain phosphatases and myotubularins belong to the tyrosine protein phosphatases superfamily. They share the presence of a conserved cysteine residue in the consensus CX(5)RT/S. Another family consists of the inositol polyphosphate 5-phosphatase isoenzymes. The importance of these phosphoinositide phosphatases in cell regulation is illustrated by multiple examples of their implications in human diseases such as Lowe syndrome, X-linked myotubular myopathy, cancer, diabetes or bacterial infection [less ▲] Detailed reference viewed: 20 (4 ULg) Chronic mastitis-affected cows display lower lipoxin levels than acute mastitis-affected cowsBoutet, Philippe ; Bureau, Fabrice ; Degand, Guy et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 23 (8 ULg) Effects of glycopyrrolate inhalation on pulmonary function in heaves-affected horses in crisisArt, Tatiana ; ; Van Erck, Emmanuelle et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 38 (4 ULg) Ceramides play a critical role in spontaneous neutrophil apoptosis; Fillet, Marianne ; Gillet, Laurent et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 15 (5 ULg) Effects of thiazolidinediones on tumor necrosis factor R alpha induced inflammatory cytokine expressionDesmet, Christophe ; ; et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 11 (3 ULg) STAT5 promotes granulocyte survival during inflammationFievez, Laurence ; Desmet, Christophe ; et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 26 (4 ULg) Influence of chloride and phosphate on the binding of oxygen to canine and feline red blood cellsCambier, Carole ; ; et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 5 (0 ULg) Cadmium-induced lung inflammation in rats is associated with an increase of matrix metalloproteinases-2 and -9 activity in broncho-alveolar lavage fluid; ; et al in Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 8 (0 ULg) Oxygen consumption and blood oxygen transport in endotoxemic calvesCambier, Carole ; ; et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 14 (0 ULg) Spermine-induced modifications of intestinal urea cyclePeulen, Olivier ; Gharbi, Myriam ; et alin Pflügers Archiv : European Journal of Physiology (2004) Detailed reference viewed: 15 (3 ULg) Polyamine as innate immunity modulatorPeulen, Olivier ; ; Gharbi, Myriam et alin Pflügers Archiv : European Journal of Physiology (2004), 449 Detailed reference viewed: 21 (1 ULg) Effect of exercise on blood glutathione in healthy race horses; ; Art, Tatiana et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 26 (5 ULg) Biochemical findings associated with atypical myopathy in grazing horsesVotion, Dominique ; Delguste, Catherine ; Amory, Hélène et alin Pflügers Archiv : European Journal of Physiology (2004), 447 Detailed reference viewed: 5 (2 ULg) Anti-inflammatory effect of natural proanthocyanidins: pharmacological evaluation on in vivo models.Garbacki, Nancy ; Tits, Monique ; Damas, Jacques ![]() in Pflügers Archiv : European Journal of Physiology (2003), 446 Detailed reference viewed: 20 (1 ULg) Activation and inactivation of bradykinin in rats.Damas, Jacques ; Garbacki, Nancy ![]() in Pflügers Archiv : European Journal of Physiology (2003), 446 Detailed reference viewed: 5 (0 ULg) Use of atropine to inhibit vagally mediated baroreceptor reflex in horses undergoing dobutamine stress testSandersen, Charlotte ; Detilleux, Johann ; Delguste, Catherine et alin Pflügers Archiv : European Journal of Physiology (2003), 446(5), 4 Detailed reference viewed: 5 (2 ULg) Echocardiographic evaluation of cardiac performance during stimulation with dobutamine in conscious horses: a preliminary study.Sandersen, Charlotte ; Delguste, Catherine ; et alin Pflügers Archiv : European Journal of Physiology (2002), 444(1-2), 4 Detailed reference viewed: 4 (1 ULg) |
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