FXYD1

PURPOSE: We investigated the effects of low and high volume speed endurance training (SET), with a reduced training volume, on sprint ability, short- and long-term exercise capacity, muscle mitochondrial properties, ion transport proteins and maximal enzyme activity in highly trained athletes. METHODS: Highly-trained male cyclists (V̇O2max: 68.3 ± 5.0 mL × min-1 × kg-1, n = 24) completed six weeks of either low (SET-L; 6x30-s intervals, n = 8) or high (SET-H; 12 × 30-s intervals, n = 8) volume SET twice per week with a 30%-reduction in training volume...

Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal aging. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury since K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. We here measured the cortical extracellular K+ concentration ([K+]e) in awake wildtype mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes...

This historical review traces key discoveries regarding K+ and Na+ ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na+ ,K+ -ATPase (NKA) and exercise effects on plasma [K+ ] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K+ loss and gains in Na+ , Cl- and H2 0, then subsequently bidirectional muscle K+ and Na+ fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na+ /K+ radioisotope fluxes, [3 H]-ouabain binding and phosphatase activity...

BACKGROUND: Pulmonary hypertension (PH) consists of a heterogenous group of diseases that culminate in increased pulmonary arterial pressure and right ventricular (RV) dysfunction. We sought to investigate the role of FXYD1, a small membrane protein that modulates Na+ -K+ -ATPase function, in the pathophysiology of PH. METHODS: We mined online transcriptome databases to assess FXYD1 expression in PH. We characterized the effects of FXYD1 knock out (KO) in mice on right and left ventricular (RV and LV) function using echocardiography and measured invasive hemodynamic measurements under normal conditions and after treatment with bleomycin sulfate or chronic hypoxia to induce PH...

BACKGROUND: Female sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF) dynamics, thus impairing ICP regulation in CSF disorders such as idiopathic intracranial hypertension (IIH). The choroid plexus (CP) is the tissue producing CSF and it has been hypothesized that altered hormonal composition could affect the activity of transporters involved in CSF secretion, thus affecting ICP...

BACKGROUND: The FXYD family of ion transport regulators have emerged as important modulators of cancer progression and metastasis. However, their expression and roles in ovarian cancer (OCa) have not been systematically investigated. METHODS: The expression of FXYD genes in OCa was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), as well as independent clinical samples. The prognostic values of FXYD genes were evaluated by Kaplan-Meier and Cox regression analysis...

Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist ( dmist ), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+ ,K+ -ATPase regulator, FXYD1/Phospholemman...

BACKGROUND: Aging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive. RESULTS: Using the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females. We further constructed gene co-expression networks and identified aging-associated modules and key regulators shared by both sexes or specific to males or females...

Na+ /K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, β, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and β1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAβ1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance...

Immunoblotting is widely used in muscle physiology to determine protein regulation and abundance. However, research groups use different protocols, which may result in differential outcomes. Herein, we investigated the effect of various homogenization procedures on determination of protein abundance in human m. vastus lateralis biopsies. Furthermore, we investigated differences in abundance between young healthy males (n = 12) and type-2 diabetics (n = 4), and the effect of data normalization...

BACKGROUND: The presented study aimed to gain insights into the pathogenesis of lung cancer (LC) and provide novel bio-markers for LC by building a regulatory circular (circ) RNAmicro (mi) RNAmRNA network. MATERIALS AND METHODS: High-throughput sequencing data of circRNAs, miRNAs and mRNAs related to LC originated from GEO (Gene Expression Omnibus) database, and the differential expressions of circRNAs, miRNAs and mRNAs were screened with R language Limma. The circRNA-miRNA and miRNA-mRNA pairs were used to build the ceRNA network...

Background: The growing body of evidence indicates aberrant expression of long noncoding RNAs (lncRNAs) in breast cancer. Nevertheless, a few studies have focused on identifying key lncRNAs for patients with luminal A breast cancer. In our study, we tried to find key lncRNAs and mRNAs in luminal A breast cancer. Methods: RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in luminal A breast cancer...

FXYD1 is a key protein controlling ion channel transport. FXYD1 exerts its function by regulating Na+ /K+ -ATPase activity, mainly in brain and cardiac tissues. Alterations of the expression level of the FXYD1 protein cause diastolic dysfunction and arrhythmias in heart and decreased neuronal dendritic tree and spine formation in brain. Moreover, FXYD1, a target of MeCP2, plays a crucial role in the pathogenesis of the Rett syndrome, a neurodevelopmental disorder. Thus, the amount of FXYD1 must be strictly controlled in a tissue specific manner and, likely, during development...

The sodium-potassium ATPase (Na/K-ATPase, NKA) establishes ion gradients that facilitate many physiological functions including action potentials and secondary transport processes. NKA comprises a catalytic subunit (alpha) that interacts closely with an essential subunit (beta) and regulatory transmembrane micropeptides called FXYD proteins. In the heart, a key modulatory partner is the FXYD protein phospholemman (PLM, FXYD1), but the stoichiometry of the alpha-beta-PLM regulatory complex is unknown. Here, we used fluorescence lifetime imaging and spectroscopy to investigate the structure, stoichiometry, and affinity of the NKA-regulatory complex...

Waterborne Benzo[a]pyrene (B[a]P) pollution is a global threat to aquatic organisms. The exposure to waterborne B[a]P can disrupt the normal locomotor behavior of zebrafish (Danio rerio), however, how it affect the locomotor behavior of adult zebrafish remains unclear. Herein, B[a]P at two concentrations (0.8 μg/L and 2.0 μg/L) were selected to investigate the molecular mechanisms of the affected locomotor behavior of zebrafish by B[a]P based on transcriptome profiling. Adverse effects of B[a]P exposure affecting locomotor behavior in zebrafish were studied by RNA sequencing, and the locomotion phenotype was acquired...

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO2max ; 51 ± 6 ml/min/kg)...

[Figure: see text].

Denervation reduces the abundance of Na+,K+-ATPase (NKA) in skeletal muscle, while reinnervation increases it. Primary human skeletal muscle cells, the most widely used model to study human skeletal muscle in vitro, are usually cultured as myoblasts or myotubes without neurons and typically do not contract spontaneously, which might affect their ability to express and regulate NKA. We determined how differentiation, de novo innervation, and electrical pulse stimulation affect expression of NKA (α and β) subunits and NKA regulators FXYD1 (phospholemman) and FXYD5 (dysadherin)...

Tight regulation of the Na/K pump is essential for cellular function because this heteromeric protein builds and maintains the electrochemical gradients for Na+ and K+ that energize electrical signaling and secondary active transport. We studied the regulation of the ubiquitous human α1β1 pump isoform by five human FXYD proteins normally located in muscle, kidney, and neurons. The function of Na/K pump α1β1 expressed in Xenopus oocytes with or without FXYD isoforms was evaluated using two-electrode voltage clamp and patch clamp...

Na,K-ATPase is a membrane transporter that is critically important for skeletal muscle function. Mdx and Bla/J mice are the experimental models of Duchenne muscular dystrophy and dysferlinopathy that are known to differ in the molecular mechanism of the pathology. This study examines the function of α1- and α2-Na,K-ATPase isozymes in respiratory diaphragm and postural soleus muscles from mdx and Bla/J mice compared with control С57Bl/6 mice. In diaphragm muscles, the motor endplate structure was severely disturbed (manifested by defragmentation) in mdx mice only...