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Wen-Kai Yang, Chao-Kai Kang, An-Di Hsu, Chia-Hao Lin, Tsung-Han Lee
Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline medaka species (Oryzias dancena and O. latipes) from different natural habitats (brackish water and fresh water). In this study, we investigated the expression and association of renal FXYD12 and NKA α-subunit as well as potential functions of FXYD12 in the two medakas...
2016: International Journal of Biological Sciences
Per Loftas, Gunnar Arbman, Xiao-Feng Sun, David Edler, Erik Syk, Olof Hallbook
PURPOSE: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. MATERIALS AND METHODS: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48)...
March 2016: Radiation Oncology Journal
Elena Arystarkhova
The fundamental role of Na,K-ATPase in eukaryotic cells calls for complex and efficient regulation of its activity. Besides alterations in gene expression and trafficking, kinetic properties of the pump are modulated by reversible association with single span membrane proteins, the FXYDs. Seven members of the family are expressed in a tissue-specific manner, affecting pump kinetics in all possible permutations. This mini-review focuses on functional properties of FXYD2 studied in transfected cells, and on noteworthy and unexpected phenotypes discovered in a Fxyd2 (-∕-) mouse...
2016: Frontiers in Physiology
Irina Lubarski-Gotliv, Carol Asher, Laura A Dada, Haim Garty
The FXYD proteins are a family of small membrane proteins that share an invariant four amino acid signature motif F-X-Y-D and act as tissue-specific regulatory subunits of the Na,K-ATPase. FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing Vmax However, unlike other family members FXYD5 appears to have additional functions, which cannot be readily explained by modulation of transport kinetics...
May 20, 2016: Journal of Biological Chemistry
Chia-Hao Chang, Wen-Kai Yang, Chia-Hao Lin, Chao-Kai Kang, Cheng-Hao Tang, Tsung-Han Lee
FXYD proteins regulate Na(+)/K(+)-ATPase (NKA), which is a primary active pump that provides the driving force that triggers osmoregulatory systems in teleosts. To explore the regulatory mechanisms between FXYD and NKA in euryhaline teleosts, the expression of NKA (mRNA, protein, and activity) and FXYD11 and their interaction were examined in the gills of brackish medaka (Oryzias dancena) when transferred from brackish water (BW; 15‰) to fresh water (FW) or seawater (SW; 35‰). The mRNA expression of Odfxyd11 and Odnka-α was elevated 48h post-hypoosmotic transfer...
April 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Márta Sárközy, Gergő Szűcs, Márton Pipicz, Ágnes Zvara, Katalin Éder, Veronika Fekete, Csilla Szűcs, Judit Bárkányi, Csaba Csonka, László G Puskás, Csaba Kónya, Péter Ferdinandy, Tamás Csont
BACKGROUND: Diabetic patients have an increased risk of developing cardiovascular diseases, which are the leading cause of death in developed countries. Although multivitamin products are widely used as dietary supplements, the effects of these products have not been investigated in the diabetic heart yet. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) affects the cardiac gene expression pattern in experimental diabetes. METHODS: Two-day old male Wistar rats were injected with streptozotocin (i...
2015: Cardiovascular Diabetology
F Cornelius, M Habeck, R Kanai, C Toyoshima, S J D Karlish
The molecular activity of Na,K-ATPase and other P2 ATPases like Ca(2+)-ATPase is influenced by the lipid environment via both general (physical) and specific (chemical) interactions. Whereas the general effects of bilayer structure on membrane protein function are fairly well described and understood, the importance of the specific interactions has only been realized within the last decade due particularly to the growing field of membrane protein crystallization, which has shed new light on the molecular details of specific lipid-protein interactions...
September 2015: Biochimica et Biophysica Acta
Rocío Retamales-Ortega, Carlos P Vio, Nibaldo C Inestrosa
P2C-type ATPases are a subfamily of P-type ATPases comprising Na(+)/K(+)-ATPase and H(+)/K(+)-ATPase. Na(+)/K(+)-ATPase is ubiquitously expressed and has been implicated in several neurological diseases, whereas H(+)/K(+)-ATPase is found principally in the colon, stomach, and kidney. Both ATPases have two subunits, α and β, but Na(+)/K(+)-ATPase also has a regulatory subunit called FXYD, which has an important role in cancer. The most important functions of these ATPases are homeostasis, potassium regulation, and maintaining a gradient in different cell types, like epithelial cells...
March 2016: Molecular Neurobiology
Elena Arystarkhova, Donna L Ralph, Yi Bessie Liu, Richard Bouley, Alicia A McDonough, Kathleen J Sweadner
Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression...
December 1, 2014: Physiological Reports
Pan Hu, Siqi Li, Yong Zhong, Xingjiang Mu, Lang Gui, Junbin Zhang
By interacting with Na(+), K(+)-ATPase (NKA), the FXYD domain-containing ion transport regulator (FXYD) is involved in teleost osmoregulation, but knowledge of FXYD in marine fish is limited. In the present study, fxyd11 and fxyd12 were identified from the spotted scat (Scatophagus argus), and the two members of the FXYD protein family were expressed in a tissue-specific manner. Fxyd11 mRNA was predominantly expressed in gills, whereas fxyd12 mRNA was mainly distributed in kidneys and intestines. Acute hyposaline stress altered the activity of NKA and the expression of fxyd11 and fxyd12 in gills, kidneys, and intestines...
August 2014: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Surajit Pathak, Wen-Jian Meng, Hong Zhang, Sebastian Gnosa, Suman Kumar Nandy, Gunnar Adell, Birgitta Holmlund, Xiao-Feng Sun
BACKGROUND: Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT...
2014: PloS One
Qian Gao, Xiongfei Chen, Hongxia Duan, Zhaoqing Wang, Jing Feng, Dongling Yang, Lina Song, Ningxin Zhou, Xiyun Yan
FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC...
July 2014: Protein & Cell
Xiongfei Chen, Mingzhu Sun, Yazhuo Hu, Honghong Zhang, Zhanbo Wang, Ningxin Zhou, Xinyun Yan
Members of the FXYD domain-containing ion transport regulator protein family, including FXYD3 and FXYD5, play an important role in the pathogenesis of numerous tumors. However, the correlation between the expression of FXYD6 and tumors remains poorly understood. In the current study, the expression of FXYD6 was examined immunohistochemically in 72 cholangiocarcinoma tissues and 30 distal normal bile duct tissues matched with the tumors. The results show that the positive expression rate of FXYD6 was significantly higher in cholangiocarcinoma than that in normal bile duct tissue (69 vs...
February 2014: Oncology Letters
Chun-Yu Chang, Cheng-Hao Tang, Yi-Hong Hsin, Hsing-Tzu Lai, Tsung-Han Lee
Na(+)/K(+)-ATPase (NKA) is a widely found and important transporter in mammals. The kidney is a major osmoregulatory organ of which the proximal tubules play a crucial role in the maintenance of ionic homeostasis functioning via salt and water reabsorption. FXYD (FXYD domain-containing protein) 2, the γ-subunit of NKA, is the first identified and the most abundant member of FXYD family, affecting the sodium/potassium affinity of NKA in the kidney. Based on DNA microarray analysis, the expression levels of fxyd2 gene are markedly increased upon hypertonic challenge...
January 2014: Journal of Membrane Biology
Zhen-Long Zhu, Bao-Yong Yan, Yu Zhang, Yan-Hong Yang, Ming-Wei Wang, Hanswalter Zentgraf, Xiang-Hong Zhang, Xiao-Feng Sun
OBJECTIVE: To investigate the association of FXYD-3 expression with clinicopathological variables and PINCH in patients with ESCC. PATIENTS AND METHODS: Expression of FXYD-3 protein was immunohistochemically examined in normal esophageal mucous (n = 20) and ESCC (n = 64). RESULTS: Expression of FXYD-3 in the cytoplasm markedly increased from normal esophageal epithelial cells to primary ESCC (P = 0.001). The expression of FXYD-3 was correlated with TNM stages and depth of tumor invasion...
2013: Disease Markers
Chia-Chi Liu, Keyvan Karimi Galougahi, Robert M Weisbrod, Thomas Hansen, Ramtin Ravaie, Andrea Nunez, Yi B Liu, Natasha Fry, Alvaro Garcia, Elisha J Hamilton, Kathleen J Sweadner, Richard A Cohen, Gemma A Figtree
Glutathionylation of the Na(+)-K(+) pump's β1-subunit is a key molecular mechanism of physiological and pathophysiological pump inhibition in cardiac myocytes. Its contribution to Na(+)-K(+) pump regulation in other tissues is unknown, and cannot be assumed given the dependence on specific β-subunit isoform expression and receptor-coupled pathways. As Na(+)-K(+) pump activity is an important determinant of vascular tone through effects on [Ca(2+)]i, we have examined the role of oxidative regulation of the Na(+)-K(+) pump in mediating angiotensin II (Ang II)-induced increases in vascular reactivity...
December 2013: Free Radical Biology & Medicine
Petr Babula, Michal Masarik, Vojtech Adam, Ivo Provaznik, Rene Kizek
The cardiac glycosides are a group of compounds isolated from plants and some animals. They have been used in therapy for heart failure for many years. The cytotoxic effect of many cardiac glycosides has been demonstrated, but the mechanism of action is very complicated and complex, and Na+/K+-ATPase surely plays a crucial role in it. On the other hand, Na+/K+-ATPase is regulated by many endogenous factors, such as hormones or FXYD proteins, whose role in regulating the cell cycle has been studied intensively...
September 2013: Anti-cancer Agents in Medicinal Chemistry
Wen-Bo Deng, Zhen Tian, Xiao-Huan Liang, Bao-Chen Wang, Feng Yang, Zeng-Ming Yang
Luminal closure and embryo apposition are essential for blastocyst attachment during early pregnancy. In our preliminary microarray results (unpublished data), sodium-potassium adenosine triphosphatase (Na/K-ATPase) β1 (Atp1b1) was highly expressed in mouse uterus on Days 3 and 4 of pregnancy. However, expression and regulation of Atp1b1 in the mammalian uterus during early pregnancy are unknown. Using in situ hybridization, a strong level of Atp1b1 mRNA was detected in luminal epithelial cells on Days 3 and 4 of pregnancy (Day 1 = day of vaginal plug)...
May 2013: Theriogenology
Haim Haviv, Michael Habeck, Ryuta Kanai, Chikashi Toyoshima, Steven J D Karlish
Membrane proteins interact with phospholipids either via an annular layer surrounding the transmembrane segments or by specific lipid-protein interactions. Although specifically bound phospholipids are observed in many crystal structures of membrane proteins, their roles are not well understood. Na,K-ATPase is highly dependent on acid phospholipids, especially phosphatidylserine, and previous work on purified detergent-soluble recombinant Na,K-ATPase showed that phosphatidylserine stabilizes and specifically interacts with the protein...
April 5, 2013: Journal of Biological Chemistry
Baoman Li, Leif Hertz, Liang Peng
Evidence accumulating during almost 50 years suggests Na(+), K(+)-ATPase dysfunction in bipolar disorder, a disease treatable with chronic administration of lithium salts, carbamazepine or valproic acid. Three Na(+), K(+)-ATPase α subunits (α1-3) and two β subunits (β1 and β2) are expressed in brain together with the auxiliary protein FXYD7. FXYD7 decreases K(+) affinity, and thus contributes to stimulation of the enzyme at elevated extracellular K(+) concentrations. Na(+), K(+)-ATPase subtype and FXYD7 genes were determined by RT-PCR in mice co-expressing one fluorescent signal with an astrocytic marker or a different fluorescent signal with a neuronal marker and treated for 14 days with carbamazepine...
April 2013: Neurochemical Research
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