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Rachel V Floyd, Ali Mobasheri, Susan Wray
Developmental and tissue-specific differences in isoforms allow Na+, K+-ATPase function to be tightly regulated, as they control sensitivity to ions and inhibitors. Uterine contraction relies on the activity of the Na+, K+ATPase, which creates ionic gradients that drive excitation-contraction coupling. It is unknown whether Na+, K+ATPase isoforms are regulated throughout pregnancy or whether they have a direct role in modulating uterine contractility. We hypothesized that gestation-dependent differential expression of isoforms would affect contractile responses to Na+, K+ATPase α subunit inhibition with ouabain...
December 2017: Physiological Reports
Elena Arystarkhova, Richard Bouley, Yi Bessie Liu, Kathleen J Sweadner
The final adjustment of urine volume occurs in the inner medullary collecting duct (IMCD), chiefly mediated by the water channel aquaporin 2 (AQP2). With vasopressin stimulation, AQP2 accumulation in the apical plasma membrane of principal cells allows water reabsorption from the lumen. We report that FXYD1 (phospholemman), better known as a regulator of Na,K-ATPase, has a role in AQP2 trafficking. Daytime urine of Fxyd1 knockout mice was more dilute than WT despite similar serum vasopressin, but both genotypes could concentrate urine during water deprivation...
2017: PloS One
Magni Mohr, Tobias Schmidt Nielsen, Pál Weihe, Jákup A Thomsen, Giovanna Aquino, Peter Krustrup, Nikolai B Nordsborg
It was evaluated whether upper-body compared to lower-body musculature exhibits a different phenotype in relation to capacity for handling reactive oxygen species (ROS), H(+), La(-), Na(+), K(+) and also whether it differs in adaptive potential to exercise training. Eighty-three sedentary premenopausal women aged 45 ± 6 years (mean ± SD) were randomized into a high-intensity intermittent swimming group (HIS, n = 21), a moderate-intensity swimming group (MOS, n = 21), a soccer group (SOC, n = 21), or a control group (CON, n = 20)...
October 2017: Physiological Reports
Dylan J Meyer, Craig Gatto, Pablo Artigas
Primary aldosteronism, a condition in which too much aldosterone is produced and that leads to hypertension, is often initiated by an aldosterone-producing adenoma within the zona glomerulosa of the adrenal cortex. Somatic mutations of ATP1A1, encoding the Na/K pump α1 subunit, have been found in these adenomas. It has been proposed that a passive inward current transported by several of these mutant pumps is a "gain-of-function" activity that produces membrane depolarization and concomitant increases in aldosterone production...
November 6, 2017: Journal of General Physiology
Casper Skovgaard, Nicki Winfield Almquist, Thue Kvorning, Peter Møller Christensen, Jens Bangsbo
The effect of tapering following a period of high-volume sprint interval training (SIT) and a basic volume of aerobic training on performance and muscle adaptations in moderately trained runners was examined. Eleven (8 males, 3 females) runners (maximum oxygen uptake (VO2-max): 56.8±2.9 mL·min(-1)·kg(-1); mean±SD) conducted high-volume SIT (HV; 20 SIT sessions; 8-12 x 30-s all-out) for 40 days followed by 18 days of tapering (TAP; 4 SIT sessions; 4 x 30-s all-out). Before and after HV as well as midway through and at the end of TAP, the subjects completed a 10-km running test and a repeated running test at 90% of vVO2-max to exhaustion (RRT)...
September 21, 2017: Journal of Applied Physiology
Ying-Ying Chen, Xiao-Ying Wang, Qiu-Xia Fu, Yi Kang, He-Bin Yao
The pathogenesis of hypokalemic periodic paralysis (HypoPP) remains unclear. Though some mutations in skeletal muscle ion channels were revealed previously, the exact mechanism remains to be fully elucidated. Increased Na(+)/K(+)-ATPase activity in skeletal muscle is postulated to contribute to attacks of HypoPP. Before the link between Na(+)/K(+)-ATPase dysfunction and these ion channel mutations is established, mutations in Na(+)/K(+)-ATPase and their regulators are the first to be excluded. Phospholemman, which is a protein encoded by the FXYD domain-containing ion transport regulator 1 (FXYD1) gene, is predominantly expressed in skeletal muscle and is the major regulator of Na(+)/K(+)-ATPase...
October 2017: Experimental and Therapeutic Medicine
Sergej Pirkmajer, Henriette Kirchner, Leonidas S Lundell, Pavel V Zelenin, Juleen R Zierath, Kira S Makarova, Yuri I Wolf, Alexander V Chibalin
KEY POINTS: Small transmembrane proteins such as FXYDs, which interact with Na(+) ,K(+) -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca(2+) -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage...
July 15, 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
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