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Université de Fribourg

Parvalbumin: calcium and magnesium buffering in the distal nephron

Olinger, Eric ; Schwaller, Beat ; Loffing, Johannes ; Gailly, Philippe ; Devuys, Olivier

In: Nephrology Dialysis Transplantation, 2012, vol. 27, no. 11, p. 3988-3994

Parvalbumin (PV) is a classical member of the EF-hand protein superfamily that has been described as a Ca²⁺ buffer and Ca²⁺ transporter/shuttle protein and may also play an additional role in Mg²⁺ handling. PV is exclusively expressed in the early part of the distal convoluted tubule in the human and mouse kidneys. Recent studies in Pvalb knockout mice revealed a role of PV in...

Université de Fribourg

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

Ackermann, Daniel ; Gresko, Nikolay ; Carrel, Monique ; Loffing-Cueni, Dominique ; Habermehl, Daniel ; Gomez-Sanchez, Celso ; Rossier, Bernard C. ; Loffing, Johannes

In: American Journal of Physiology - Renal Physiology, 2011, vol. 299, no. 6, p. F1473-F1485

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2...

Université de Fribourg

αENaC mediated lithium absorption promotes nephrogenic diabetes insipidus

Mønster Christensen, Birgitte ; Mercier Zuber, Annie ; Loffing, Johannes ; Stehle, Jean-Christophe ; Deen, Peter M.T. ; Rossier, Bernard C. ; Hummler, Edith

In: Journal of the American Society of Nephrology, 2010, vol. 21, p. -

Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic...

Université de Fribourg

Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins

Wagner, Carsten A. ; Loffing-Cueni, Dominique ; Yan, Qingshang ; Schulz, Nicole ; Fakitsas, Panagiotis ; Carrel, Monique ; Wang, Tong ; Verrey, François ; Geibel, John P. ; Giebisch, Gerhard ; Hebert, Steven C. ; Loffing, Johannes

In: American Journal of Physiology: Renal Physiology, 2008, vol. 294, no. 6, p. F1373-F1380

ROMK-deficient (Romk–/–) mice exhibit polyuria, natriuresis, and kaliuresis similar to individuals with type II Bartter's form of hyperprostaglandin E syndrome (HPS; antenatal Bartter's syndrome). In the present study, we utilized both metabolic and clearance studies to define the contributions of specific distal nephron segments to the renal salt wasting in these mice. The...

Université de Fribourg

Renal expression of parvalbumin is critical for NaCl handling and response to diuretics

Belge, Hendrica ; Gailly, Philippe ; Schwaller, Beat ; Loffing, Johannes ; Debaix, Huguette ; Riveira-Munoz, Eva ; Beauwens, Renaud ; Devogelaer, Jean-Pierre ; Hoenderop, Joost G. ; Bindels, René J. ; Devuyst, Olivier

In: Proceedings of the National Academy of Sciences of the United States of America, 2007, vol. 104, no. 37, p. 14849-14854

The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca²⁺-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice...

Université de Fribourg

Replication of segment-specific and intercalated cells in the mouse renal collecting system

Wehrli, Philipp ; Loffing-Cueni, Dominique ; Kaissling, Brigitte ; Loffing, Johannes

In: Histochemistry and Cell Biology, 2007, vol. 127, no. 4, p. 389-398

The renal collecting system (CS) is composed of segment-specific (SS) and intercalated (IC) cells. The latter comprise at least two subtypes (type A and non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is unclear. Among other hypotheses, it was proposed that one subtype of IC cells represents a stem cell population from which all cell types in the CS may arise. In...

Université de Fribourg

Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal collecting system

Loffing-Cueni, Dominique ; Flores, Sandra Y. ; Sauter, Daniel ; Daidié, Dorothée ; Siegrist, Nicole ; Meneton, Pierre ; Staub, Olivier ; Loffing, Johannes

In: Journal of the American Society of Nephrology, 2006, vol. 17, p. 1264-1274

The activity of the epithelial sodium (Na⁺) channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) needs to be tightly regulated to match urinary Na⁺ excretion with dietary Na⁺ intake. The ubiquitin-protein ligase Nedd4-2, which in vitro interacts with ENaC subunits and reduces ENaC cell surface abundance and activity by ubiquitylation of the channel, may participate in...

Université de Fribourg

Progesterone down-regulates the open probability of the amiloride-sensitive epithelial sodium channel via a Nedd4-2-dependent mechanism

Michlig, Stéphanie ; Harris, Michael ; Loffing, Johannes ; Rossier, Bernard C. ; Firsov, Dmitri

In: Journal of Biological Chemistry, 2005, vol. 280(46), p. 38264

Activation of the mitogen-activated protein (MAP) kinase cascade by progesterone in Xenopus oocytes leads to a marked down-regulation of activity of the amiloride-sensitive epithelial sodium channel (ENaC). Here we have studied the signaling pathways involved in progesterone effect on ENaC activity. We demonstrate that: (i) the truncation of the C termini of the αβγENaC subunits results...