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https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#1
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27909897/nha2-is-expressed-in-distal-nephron-and-regulated-by-dietary-sodium
#2
Kalyan C Kondapalli, R Todd Alexander, Jennifer L Pluznick, Rajini Rao
Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na(+)(Li(+))/H(+) antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H(+)-coupled Na(+)(Li(+)) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2...
December 1, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27892464/wnt5a-induces-renal-aqp2-expression-by-activating-calcineurin-signalling-pathway
#3
Fumiaki Ando, Eisei Sohara, Tetsuji Morimoto, Naofumi Yui, Naohiro Nomura, Eriko Kikuchi, Daiei Takahashi, Takayasu Mori, Alain Vandewalle, Tatemitsu Rai, Sei Sasaki, Yoshiaki Kondo, Shinichi Uchida
Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27889609/aquaporin-2-ser-261-phosphorylation-is-regulated-in-combination-with-ser-256-and-ser-269-phosphorylation
#4
Naofumi Yui, Sei Sasaki, Shinichi Uchida
Aquaporin-2 (AQP2) is a water channel in collecting duct principal cells in the kidney. Vasopressin catalyzes AQP2 phosphorylation at several serine sites in its C-terminus: Ser-256, Ser-261, and Ser-269. Upon stimulation by vasopressin, Ser-269 phosphorylation increases and Ser-261 phosphorylation decreases. Ser-256 phosphorylation is relatively constant. However, whether these types of phospho-regulation occur independently in distinct AQP2 populations or sequentially in the same AQP2 population is unclear...
November 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27865300/effect-of-dapagliflozin-treatment-on-fluid-and-electrolyte-balance-in-diabetic-rats
#5
Ling Chen, Lauren M LaRocque, Orhan Efe, Juan Wang, Jeff M Sands, Janet D Klein
AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na(+), K(+), Cl(-) concentration, urine Na(+), K(+), Cl(-) excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin...
November 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27849390/adverse-effects-of-tempol-on-hidrosaline-balance-in-rats-with-acute-sodium-overload
#6
N M Kouyoumdzian, Nl Rukavina Mikusic, G Cao, M R Choi, Sl Della Penna, B E Fernández, J E Toblli, M I Rosón
We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue...
November 2016: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/27801846/aqp2-plasma-membrane-diffusion-is-altered-by-the-degree-of-aqp2-s256-phosphorylation
#7
Eva C Arnspang, Frédéric H Login, Jennifer S Koffman, Prabuddha Sengupta, Lene N Nejsum
Fine tuning of urine concentration occurs in the renal collecting duct in response to circulating levels of arginine vasopressin (AVP). AVP stimulates intracellular cAMP production, which mediates exocytosis of sub-apical vesicles containing the water channel aquaporin-2 (AQP2). Protein Kinase A (PKA) phosphorylates AQP2 on serine-256 (S256), which triggers plasma membrane accumulation of AQP2. This mediates insertion of AQP2 into the apical plasma membrane, increasing water permeability of the collecting duct...
October 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27793629/microsecond-simulation-of-human-aquaporin-2-reveals-structural-determinants-of-water-permeability-and-selectivity
#8
Siladitya Padhi, U Deva Priyakumar
Human aquaporin 2 (AQP2) from the family of aquaporins assumes great physiological importance, owing to its association with nephrogenic diabetes insipidus (NDI). The present study provides detailed insights into the transport properties of AQP2 with the use of microsecond-scale molecular dynamics simulations, and explains how these channels conduct water molecules while at the same time excluding other molecules. Water transport is seen to be diffusion-limited, with a barrier of only 1.6kcalmol(-1), and the channel is more water-permeable than other known aquaporins...
October 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27788793/tissue-expression-of-aquaporin-2-is-correlated-to-urine-output-and-allograft-function-in-sensitized-kidney-transplant-patients
#9
K Klein, S Rübenacker, S M Schaefer, L P Kihm, V Schwenger, S Macher-Goeppinger, P Schemmer, C Süsald, M Zeier, C Morath, L E Becker
BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68)...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27784697/outside-the-mainstream-novel-collecting-duct-proteins-regulating-water-balance
#10
Shamma S Rahman, Erika I Boesen
Body water balance is critical to survival and therefore very tightly regulated by the hypothalamus and kidney. A key mechanism involved in this process, the arginine vasopressin (AVP)-mediated phosphorylation and apical membrane insertion of aquaporin 2 (AQP2) in the collecting duct, has been extensively studied; however, with the increased availability of conditional knockout animals, several novel collecting duct proteins have recently been implicated in water homeostasis. In this Mini-Review, we briefly discuss these novel proteins and their roles in the regulation of water homeostasis...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#11
Sophia LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27763558/involvement-of-jnk-nf%C3%AE%C2%BAb-signaling-pathways-in-the-lipopolysaccharide-induced-modulation-of-aquaglyceroporin-expression-in-3t3-l1-cells-differentiated-into-adipocytes
#12
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
https://www.readbyqxmd.com/read/27760771/molecular-mechanisms-regulating-aquaporin-2-in-kidney-collecting-duct
#13
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
https://www.readbyqxmd.com/read/27760768/ilk-and-cytoskeletal-architecture-an-important-determinant-of-aqp2-recycling-and-subsequent-entry-into-the-exocytotic-pathway
#14
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
https://www.readbyqxmd.com/read/27753955/os-08-05-novel-molecular-insights-in-urinary-exosome-protein-profiling-in-thiazide-induced-hyponatremia
#15
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
https://www.readbyqxmd.com/read/27733367/depletion-of-vacuolar-protein-sorting-associated-protein-35-is-associated-with-increased-lysosomal-degradation-of-aquaporin-2
#16
Mi Suk Lee, Hyo-Jung Choi, Eui-Jung Park, Hye-Jeong Park, Tae-Hwan Kwon
The carboxyl terminus of aquaporin-2 (AQP2c) undergoes posttranslational modifications, including phosphorylation and ubiquitination, in the process of regulating aquaporin-2 (AQP2) translocation and protein abundance. We aimed to identify novel proteins interacting with AQP2c. Recombinant AQP2c protein was made in Escherichia coli BL21 (DE3) cells 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...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27725713/systems-level-analysis-reveals-selective-regulation-of-aqp2-gene-expression-by-vasopressin
#17
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
https://www.readbyqxmd.com/read/27694161/egf-receptor-inhibition-by-erlotinib-increases-aquaporin-2-mediated-renal-water-reabsorption
#18
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
https://www.readbyqxmd.com/read/27681727/disruption-of-membranes-of-extracellular-vesicles-is-necessary-for-elisa-determination-of-urine-aqp2-proof-of-disruption-and-epitopes-of-aqp2-antibodies
#19
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...
September 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27649563/signaling-modification-by-gpcr-heteromer-and-its-implication-on-x-linked-nephrogenic-diabetes-insipidus
#20
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
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