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Jeanne Durendale Chiadak, Tatjana Arsenijevic, Francoise Gregoire, Nargis Bolaky, Valerie Delforge, Jason Perret, Christine Delporte
Aquaglyceroporins, belonging to the family of aquaporins (AQPs), are integral plasma membrane proteins permeable to water and glycerol that have emerged as key players in obesity. The aim of this study was to investigate the expression profile of AQPs in undifferentiated and differentiated 3T3-L1 cells and to investigate the changes in expression of aquaglyceroporins in 3T3-L1 cells differentiated into adipocytes and subjected to lipopolysaccharide (LPS) mimicking inflammation occurring during obesity. Furthermore, the study aimed at identifying the signaling cascade involved in the regulation of aquaglyceroporins expression upon LPS stimulation...
October 18, 2016: International Journal of Molecular Sciences
Hyun Jun Jung, Tae-Hwan Kwon
Kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone which induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of Aqp2 gene to increase AQP2 protein abundance...
October 19, 2016: American Journal of Physiology. Renal Physiology
Fahmy A Mamuya, Jose Luis Cano-Peñalver, Wei U Li, Diego Rodriguez-Puyol, Manuel Rodríguez-Puyol, Dennis Brown, Sergio de Frutos, Hua Jenny Lu
Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, in order to open a path towards effective diabetes insipidus therapeutics. A recent study has shown that Integrin-Linked Kinase (ILK) conditional-knockdown mice developed polyuria along with decreased expression of AQP2. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Sarath Channavajjhala, Wenjing Jia, Mahli Jalland, Kevin OʼShaughnessy, Ian Hall, Mark Glover
OBJECTIVE: Thiazide diuretics are amongst most widely prescribed and effective anti-hypertensive medicines worldwide. Thiazides however cause Thiazide-Induced Hyponatremia (TIH), a novel and potentially important paradigm of dysregulated distal nephron sodium and water reabsorption. A priori TIH must result from excessive saliuresis and/or water reabsorption. The water and electrolyte transporter composition of Urinary Exosomes (UE) reflects their cellular origin and are a promising way to study renal dysfunction...
September 2016: Journal of Hypertension
Mi Suk Lee, Hyo-Jung Choi, Eui-Jung Park, Hye-Jeong Park, Tae-Hwan Kwon
Carboxyl-terminus of AQP2 (AQP2c) undergoes post-translational modifications, including phosphorylation and ubiquitination, for the regulation of aquaporin-2 (AQP2) translocation and protein abundance. We aimed to identify novel proteins interacting with AQP2c. Recombinant AQP2c protein was made in E. coli BL21 (DE3) by exploiting the pET32 TrxA fusion system. Lysates of rat kidney inner medullary collecting duct (IMCD) tubule suspensions interacted with rat AQP2c bound to Ni(2+)-resin were subjected to LC-MS/MS proteomic analysis...
October 12, 2016: American Journal of Physiology. Renal Physiology
Pablo C Sandoval, J'Neka S Claxton, Jae Wook Lee, Fahad Saeed, Jason D Hoffert, Mark A Knepper
Vasopressin-mediated regulation of renal water excretion is defective in a variety of water balance disorders in humans. It occurs in part through long-term mechanisms that regulate the abundance of the aquaporin-2 water channel in renal collecting duct cells. Here, we use deep DNA sequencing in mouse collecting duct cells to ask whether vasopressin signaling selectively increases Aqp2 gene transcription or whether it triggers a broadly targeted transcriptional network. ChIP-Seq quantification of binding sites for RNA polymerase II was combined with RNA-Seq quantification of transcript abundances to identify genes whose transcription is regulated by vasopressin...
October 11, 2016: Scientific Reports
Pui W Cheung, Naohiro Nomura, Anil V Nair, Nutthapoom Pathomthongtaweechai, Lars Ueberdiek, Hua A Jenny Lu, Dennis Brown, Richard Bouley
Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high-throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output...
October 2016: Journal of the American Society of Nephrology: JASN
Masaaki Nameta, Yoko Saijo, Yasukazu Ohmoto, Kiyonori Katsuragi, Keiko Yamamoto, Tadashi Yamamoto, Kenichi Ishibashi, Sei Sasaki
Aquaporin-2 (AQP2) is present in urine extracellular vesicles (EVs) and is a useful biomarker for water balance disorders. We previously found that pre-treatment of urine with alkali/detergent or storage at -25 °C is required for enzyme-linked immunosorbent assay (ELISA) measurement. We speculated that disruptions of EVs membranes are necessary to allow for the direct contact of antibodies with their epitopes. Human urine EVs were prepared using an ultracentrifugation method. Urine EV samples were stored at different temperatures for a week...
2016: International Journal of Molecular Sciences
Hans K H Ng, Kaleeckal G Harikumar, Laurence J Miller, Billy K C Chow
The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT's potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear...
2016: PloS One
Sarath Channavajjhala, Wenjing Jia, Mahli Jalland, Kevin OʼShaughnessy, Ian Hall, Mark Glover
OBJECTIVE: Thiazide diuretics are amongst most widely prescribed and effective anti-hypertensive medicines worldwide. Thiazides however cause Thiazide-Induced Hyponatremia (TIH), a novel and potentially important paradigm of dysregulated distal nephron sodium and water reabsorption. A priori TIH must result from excessive saliuresis and/or water reabsorption. The water and electrolyte transporter composition of Urinary Exosomes (UE) reflects their cellular origin and are a promising way to study renal dysfunction...
September 2016: Journal of Hypertension
Abdulah El Tarazi, Yoann Lussier, Sandra Da Cal, Pierre Bissonnette, Daniel G Bichet
Aquaporin-2 (AQP2) is a homotetrameric water channel responsible for the final water reuptake in the kidney. Mutations in the protein induce nephrogenic diabetes insipidus (NDI), which challenges the water balance by producing large urinary volumes. Although recessive AQP2 mutations are believed to generate non-functional and monomeric proteins, the literature identifies several mild mutations which suggest the existence of mixed wt/mut tetramers likely to carry function in heterozygotes. Using Xenopus oocytes, we tested this hypothesis and found that mild mutants (V24A, D150E) can associate with wt-AQP2 in mixed heteromers, providing clear functional gain in the process (62 ± 17% and 63 ± 17% increases, respectively), conversely to the strong monomeric R187C mutant which fails to associate with wt-AQP2...
2016: Scientific Reports
Graça Soveral, Angela Casini
INTRODUCTION: Since the discovery of aquaporin-1 (AQP1) as a water channel, more than 2,000 articles, reviews and chapters have been published. The wide tissue expression, functional and biological roles have documented the major and essential physiological importance of these channels both in health and disease. Thus, over the years, studies have revealed essential importance of aquaporins in mammalian pathophysiology revealing aquaporins as potential drug targets. AREAS COVERED: Starting from a brief description of the main structural and functional features of aquaporins, their roles in physiology and pathophysiology of different human diseases, this review describes the main classes of small molecules and biologicals patented, published from 2010 to 2015, able to regulate AQPs for diagnostic and therapeutic applications...
September 13, 2016: Expert Opinion on Therapeutic Patents
Galina S Baturina, Liubov E Katkova, Sotirios G Zarogiannis, Evgeniy I Solenov
Vasopressin (AVP) regulates body salt-water balance. Brattleboro rats carry an AVP gene mutation resulting in a recessive form of central diabetes insipidus, being ideal for AVP deficiency studies. Herein, we studied the water permeability of the apical and basolateral sides of outer medullary collecting duct (OMCD) principal cells in response to dDAVP (a V2 receptor agonist) administration in Wistar and Brattleboro rats. Biophysical measurements of the water permeability (Pf ) of isolated OMCD principal cells were performed with the calcein quenching method with/without dDAVP (10(-8) M)...
September 4, 2016: Clinical and Experimental Pharmacology & Physiology
Francesco Trepiccione, Christelle Soukaseum, Anna Iervolino, Federica Petrillo, Miriam Zacchia, Gunther Schütz, Dominique Eladari, Giovambattista Capasso, Juliette Hadchouel
The distal nephron is a heterogeneous part of the nephron composed by six different cell types forming the epithelium of the distal convolute (DCT), connecting (CNT) and collecting duct (CD). To dissect the function of these cells, knock out models specific for their unique cell marker have been created. However, since this part of the nephron develops at the border between the ureteric bud and the metanephric mesenchyme, the specificity of the single cell-markers has been recently questioned. Here, by mapping the fate of the AQP2, NCC-positive cells using transgenic mouse lines expressing the YFP fluorescent marker, we showed that the origin of the distal nephron is extremely composite...
August 31, 2016: American Journal of Physiology. Renal Physiology
Emma Tina Bisgaard Olesen, Hanne Bjerregaard Moeller, Mette Assentoft, Nanna MacAulay, Robert A Fenton
Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be cAMP-dependent. However, on the basis of recent reports, it was hypothesized in the current study that increased cAMP levels are not necessary for AQP2 membrane targeting. The role and dynamics of cAMP signaling on AQP2 membrane targeting in Madin-Darby Canine Kidney and mouse cortical collecting duct (mpkCCD14) cells was examined using selective agonists against the V2R (dDAVP), EP2 (butaprost) and EP4 (CAY10580)...
August 24, 2016: American Journal of Physiology. Renal Physiology
Jeff M Sands, Janet D Klein
Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for Nephrogenic Diabetes Insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter...
August 17, 2016: American Journal of Physiology. Renal Physiology
Mohammad M Al-Bataineh, Hui Li, Kazuhiro Ohmi, Fan Gong, Allison Marciszyn, Sajid Naveed, Xiaoqing Zhu, Dietbert Neumann, Qi Wu, Lei Cheng, Robert A Fenton, Núria M Pastor-Soler, Kenneth R Hallows
Aquaporin-2 (AQP2) is essential to maintain body water homeostasis. AQP2 traffics from intracellular vesicles to the apical membrane of kidney collecting duct principal cells in response to vasopressin (AVP), a hormone released with low intravascular volume, which causes decreased kidney perfusion. Decreased kidney perfusion activates AMP-activated kinase (AMPK), a metabolic sensor that inhibits the activity of several transport proteins. We hypothesized that AMPK activation also inhibits AQP2 function. These putative AMPK effects could protect interstitial ionic gradients required for urinary concentration during metabolic stress when low intravascular volume induces AVP release...
August 17, 2016: American Journal of Physiology. Renal Physiology
Karen de Carvalho Lopes, Edi Lúcia Sartorato, Sueli M da Silva-Costa, Nadya Soares de Macedo Adamov, Fernando Freitas Ganança
OBJECTIVES: Ménière's disease (MD) is a complex disease of unknown etiology characterized by a symptomatic tetrad of vertigo, hearing loss, tinnitus, and aural fullness. In addition to factors related to homeostasis of the inner ear, genetic factors have been implicated in its pathophysiology, including genes related to the transport of water and ionic composition maintenance of the endolymph, such as the aquaporin genes AQP2 and AQP3, and the potassium channel gene KCNE1. The aim of this study was to identify polymorphisms of these genes and determine their association with clinical characteristics of patients with MD...
September 2016: Otology & Neurotology
Miriam Zacchia, Enza Zacchia, Enrica Zona, Giovanna Capolongo, Ilaria Raiola, Luca Rinaldi, Francesco Trepiccione, Diego Ingrosso, Alessandra Perna, Valentina Di Iorio, Francesca Simonelli, Orson W Moe, Giovambattista Capasso
The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate < 60 ml·min(-1)·1.73 m(-2) Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency...
October 1, 2016: American Journal of Physiology. Renal Physiology
Huiwen Ren, Baoxue Yang, Joseph A Ruiz, Orhan Efe, Titilayo Omolara Ilori, Jeff M Sands, Janet D Klein
Vasopressin triggers the phosphorylation and apical plasma membrane accumulation of aquaporin 2 (AQP2), and plays an essential role in urine concentration. Vasopressin, acting through protein kinase A, phosphorylates AQP2. However, the phosphorylation state of AQP2 could also be affected by the action of protein phosphatases (PPs). Rat inner medullas (IM) were incubated with calyculin (PP1 and PP2A inhibitor, 50 nM) or tacrolimus (PP2B inhibitor, 100 nM). Calyculin did not affect total AQP2 protein abundance (by Western blot) but did significantly increase the abundances of pS256-AQP2 and pS264-AQP2...
August 3, 2016: American Journal of Physiology. Renal Physiology
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