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Sergej Pirkmajer, Henriette Kirchner, Leonidas Lundell, Pavel V Zelenin, Juleen R Zierath, Kira S Makarova, Yuri I Wolf, Alexander V Chibalin
Small transmembrane proteins are important for regulation of cellular ion transport. The most prominent among these proteins are members of the FXYD family (FXYD1-12), which regulate Na(+) -K(+) -ATPase, and phospholamban, sarcolipin, myoregulin, and DWORF, which regulate the sarco-endoplasmic reticulum Ca(2+) -ATPase (SERCA). FXYDs and regulators of SERCA are present in fishes, as well as terrestrial vertebrates; however, their evolutionary origins and phylogenetic relationships are obscure, thus hampering comparative physiological studies...
April 24, 2017: Journal of Physiology
Casper Skovgaard, Nicki Winfield Almquist, Jens Bangsbo
The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, 18 male (n = 14) and female (n = 4) runners (V̇o2max: 57.3 ± 3.4 ml/min; means ± SD) completed 20 sessions of maintained low-frequency (LF; every fourth day; n = 7) or high-frequency (HF; every second day; n = 11) SET. Before FAM as well as before and after an intervention period (INT), subjects completed a series of running tests and a biopsy from m...
January 1, 2017: Journal of Applied Physiology
Robert Busch, Weiliang Qiu, Jessica Lasky-Su, Jarrett Morrow, Gerard Criner, Dawn DeMeo
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide. Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility. We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort...
November 5, 2016: Respiratory Research
Anders Kalsen, Morten Hostrup, Vibeke Backer, Jens Bangsbo
The aim was to investigate the effect of the long-acting β2-adrenergic agonist formoterol on muscle strength and power output, muscle metabolism, and phosphorylation of CaMKII Thr(287) and FXYD1 during maximal sprinting. In a double-blind crossover study, 13 males [V̇o2 max: 45.0 ± 0.2 (means ± SE) ml·min(-1)·kg(-1)] performed a 30-s cycle ergometer sprint after inhalation of either 54 μg of formoterol (FOR) or placebo (PLA). Before and after the sprint, muscle biopsies were collected from vastus lateralis and maximal voluntary contraction (MVC), and contractile properties of quadriceps were measured...
June 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Martin Thomassen, Thomas P Gunnarsson, Peter M Christensen, Davor Pavlovic, Michael J Shattock, Jens Bangsbo
The present study examined the effect of intensive training in combination with marked reduction in training volume on phospholemman (FXYD1) expression and phosphorylation at rest and during exercise. Eight well-trained cyclists replaced their regular training with speed-endurance training (10-12 × ∼30-s sprints) two or three times per week and aerobic high-intensity training (4-5 × 3-4 min at 90-95% of peak aerobic power output) 1-2 times per week for 7 wk and reduced the training volume by 70%. Muscle biopsies were obtained before and during a repeated high-intensity exercise protocol, and protein expression and phosphorylation were determined by Western blot analysis...
April 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Christopher M Stanley, Dominique G Gagnon, Adam Bernal, Dylan J Meyer, Joshua J Rosenthal, Pablo Artigas
Cardiac cells express more than one isoform of the Na, K-ATPase (NKA), the heteromeric enzyme that creates the Na(+) and K(+) gradients across the plasmalemma. Cardiac isozymes contain one catalytic α-subunit isoform (α1, α2, or α3) associated with an auxiliary β-subunit isoform (β1 or β2). Past studies using biochemical approaches have revealed minor kinetic differences between isozymes formed by different α-β isoform combinations; these results make it difficult to understand the physiological requirement for multiple isoforms...
November 3, 2015: Biophysical Journal
Palanikumar Manoharan, Tatiana L Radzyukevich, Hesamedin Hakim Javadi, Cory A Stiner, Julio A Landero Figueroa, Jerry B Lingrel, Judith A Heiny
The Na(+)-K(+)-ATPase α2-isoform in skeletal muscle is rapidly stimulated during muscle use and plays a critical role in fatigue resistance. The acute mechanisms that stimulate α2-activity are not completely known. This study examines whether phosphorylation of phospholemman (PLM/FXYD1), a regulatory subunit of Na(+)-K(+)-ATPase, plays a role in the acute stimulation of α2 in working muscles. Mice lacking PLM (PLM KO) have a normal content of the α2-subunit and show normal exercise capacity, in contrast to the greatly reduced exercise capacity of mice that lack α2 in the skeletal muscles...
December 15, 2015: American Journal of Physiology. Cell Physiology
Magni Mohr, Martin Thomassen, Olivier Girard, Sebastien Racinais, Lars Nybo
PURPOSE: To examine how match performance parameters in trained footballers relate to skeletal muscle parameters, sprint ability and intermittent exercise performance. METHODS: 19 male elite football players completed an experimental game with physical performance determined by video analysis and exercise capacity assessed by intermittent Yo-Yo IR1 and IR2 tests, and a repeated sprint test (RST). Muscle tissue was obtained for analysis of metabolic enzyme maximal activity and key muscle protein expression...
February 2016: European Journal of Applied Physiology
Łukasz A Wujak, Anna Blume, Emel Baloğlu, Małgorzata Wygrecka, Jegor Wygowski, Susanne Herold, Konstantin Mayer, István Vadász, Petra Besuch, Heimo Mairbäurl, Werner Seeger, Rory E Morty
Acute respiratory distress syndrome (ARDS) is clinical syndrome characterized by decreased lung fluid reabsorption, causing alveolar edema. Defective alveolar ion transport undertaken in part by the Na(+)/K(+)-ATPase underlies this compromised fluid balance, although the molecular mechanisms at play are not understood. We describe here increased expression of FXYD1, FXYD3 and FXYD5, three regulatory subunits of the Na(+)/K(+)-ATPase, in the lungs of ARDS patients. Transforming growth factor (TGF)-β, a pathogenic mediator of ARDS, drove increased FXYD1 expression in A549 human lung alveolar epithelial cells, suggesting that pathogenic TGF-β signaling altered Na(+)/K(+)-ATPase activity in affected lungs...
January 2016: Respiratory Physiology & Neurobiology
Michael Habeck, Haim Haviv, Adriana Katz, Einat Kapri-Pardes, Sophie Ayciriex, Andrej Shevchenko, Haruo Ogawa, Chikashi Toyoshima, Steven J D Karlish
The activity of membrane proteins such as Na,K-ATPase depends strongly on the surrounding lipid environment. Interactions can be annular, depending on the physical properties of the membrane, or specific with lipids bound in pockets between transmembrane domains. This paper describes three specific lipid-protein interactions using purified recombinant Na,K-ATPase. (a) Thermal stability of the Na,K-ATPase depends crucially on a specific interaction with 18:0/18:1 phosphatidylserine (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-L-serine; SOPS) and cholesterol, which strongly amplifies stabilization...
February 20, 2015: Journal of Biological Chemistry
Hansraj Dhayan, Anwar R Baydoun, Andreas Kukol
G-quadruplexes are higher-order nucleic acid structures formed of square-planar arrangements of four guanine bases held together by Hoogsteen-type hydrogen bonds. Stacks of guanine tetrads are stabilised by intercalating potassium ions. FXYD1 encodes for phospholemman, a regulatory subunit of the cardiac Na(+)/K(+)-ATPase. Computational sequence analysis of FXYD1 pre-mRNA predicted the formation of stable intramolecular G-quadruplexes in human and orthologue sequences. Multiple sequence alignment indicated that G-rich sequences are conserved in evolution suggesting a potential role of G-quadruplexes in FXYD1 gene expression...
October 15, 2014: Archives of Biochemistry and Biophysics
Meenakumari Subramanian, Adam L Hunt, Giuseppe A Petrucci, Zengyi Chen, Edith D Hendley, Bradley M Palmer
The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction...
July 2014: Journal of Trace Elements in Medicine and Biology
Erica Cirri, Corinna Kirchner, Simon Becker, Adriana Katz, Steven J Karlish, Hans-Jürgen Apell
The human α1/His10-β1 isoform of Na,K-ATPase has been reconstituted as a complex with and without FXYD1 into proteoliposomes of various lipid compositions in order to study the effect of the regulatory subunit on the half-saturating Na⁺ concentration (K(½)) of Na⁺ ions for activation of the ion pump. It has been shown that the fraction of negatively charged lipid in the bilayer crucially affects the regulatory properties. At low concentrations of the negatively charged lipid DOPS (<10 %), FXYD1 increases K(½) of Na⁺ ions for activation of the ion pump...
December 2013: Journal of Membrane Biology
Ying Zhang, Renjun Wang, Weijie Du, Shuxuan Wang, Lei Yang, Zhenwei Pan, Xuelian Li, Xuehui Xiong, Hua He, Yongfang Shi, Xue Liu, Shaonan Yu, Zhengang Bi, Yanjie Lu, Hongli Shan
Estrogen deficiency is associated with increased incidence of cardiovascular diseases. But merely estrogen supplementary treatment can induce many severe complications such as breast cancer. The present study was designed to elucidate molecular mechanisms underlying increased susceptibility of arrhythmogenesis during myocardial infarction with estrogen deprivation, which provides us a new target to cure cardiac disease accompanied with estrogen deprivation. We successfully established a rat model of myocardial ischemia (MI) accompanied with estrogen deprivation by coronary artery ligation and ovariectomy (OVX)...
2013: PloS One
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
Martin Thomassen, Robyn M Murphy, Jens Bangsbo
The aim of the present study was to examine fibre type-specific Na(+)-K(+) pump subunit expression and exercise-induced alterations in phospholemman (FXYD1) phosphorylation in humans. Segments of human skeletal muscle fibres were dissected and fibre typed, and protein expression was determined by Western blotting. The protein expression of the Na(+)-K(+) pump α2 isoform was lower in type I than in type II fibres (0.63 ± 0.04 a.u. vs. 1.00 ± 0.07 a.u., P < 0.001), while protein expression of the Na(+)-K(+) pump α1 and β1 isoforms was not different...
March 15, 2013: Journal of Physiology
Valerie Matagne, Sarojini Budden, Sergio R Ojeda, Jacob Raber
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2. Several genes have been shown to be MECP2 targets. We previously identified FXYD1 (encoding phospholemman; a protein containing the motif phenylalanine-X-tyrosine-aspartate), a gene encoding a transmembrane modulator of the Na, K-ATPase (NKA) enzyme, as one of them. In the absence of MECP2, FXYD1 expression is increased in the frontal cortex (FC) of both RTT patients and Mecp2(Bird) null mice. Here, we show that Fxyd1 mRNA levels are also increased in the FC and hippocampus (HC) of male mice carrying a truncating mutation of the Mecp2 gene (Mecp2(308))...
February 16, 2013: Brain Research
Joseph Y Cheung, Xue-Qian Zhang, Jianliang Song, Erhe Gao, Tung O Chan, Joseph E Rabinowitz, Walter J Koch, Arthur M Feldman, JuFang Wang
Phospholemman (PLM) is the founding member of the FXYD family of regulators of ion transport. PLM is a 72-amino acid protein consisting of the signature PFXYD motif in the extracellular N terminus, a single transmembrane (TM) domain, and a C-terminal cytoplasmic tail containing three phosphorylation sites. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. The TM domain of PLM interacts with TM9 of the α-subunit of Na(+)-K(+)-ATPase, while its cytoplasmic tail interacts with two small regions (spanning residues 248-252 and 300-304) of the proximal intracellular loop of Na(+)/Ca(2+) exchanger...
2013: Advances in Experimental Medicine and Biology
Emily S Wan, Weiliang Qiu, Andrea Baccarelli, Vincent J Carey, Helene Bacherman, Stephen I Rennard, Alvar Agustí, Wayne H Anderson, David A Lomas, Dawn L DeMeo
RATIONALE: Systemic glucocorticoids are used therapeutically to treat a variety of medical conditions. Epigenetic processes such as DNA methylation may reflect exposure to glucocorticoids and may be involved in mediating the responses and side effects associated with these medications. OBJECTIVES: To test the hypothesis that differences in DNA methylation are associated with current systemic steroid use. METHODS: We obtained DNA methylation data at 27,578 CpG sites in 14,475 genes throughout the genome in two large, independent cohorts: the International COPD Genetics Network (n(discovery) = 1,085) and the Boston Early Onset COPD study (n(replication) = 369)...
December 15, 2012: American Journal of Respiratory and Critical Care Medicine
Jessica T Chang, Laura Anne Lowery, Hazel Sive
Formation of the vertebrate brain ventricles requires both production of cerebrospinal fluid (CSF), and its retention in the ventricles. The Na,K-ATPase is required for brain ventricle development, and we show here that this protein complex impacts three associated processes. The first requires both the alpha subunit (Atp1a1) and the regulatory subunit, Fxyd1, and leads to formation of a cohesive neuroepithelium, with continuous apical junctions. The second process leads to modulation of neuroepithelial permeability, and requires Atp1a1, which increases permeability with partial loss of function and decreases it with overexpression...
August 15, 2012: Developmental Biology
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