Article
Transplantation
Giovanna Capolongo, Sara Damiano, Yoko Suzumoto, Miriam Zacchia, Maria Rizzo, Enrica Zona, Rosa Maria Pollastro, Mariadelina Simeoni, Roberto Ciarcia, Francesco Trepiccione, Giovambattista Capasso
Summary: This study investigates the nephrotoxicity of cyclosporin A (CsA), a drug used for immuno-suppression, and its association with hypertension. The findings suggest that up-regulation of the sodium transporter NKCC2 in the renal tubules contributes to sodium retention and the development of CsA-induced hypertension. These results were observed in both CsA-treated rats and kidney-transplanted patients receiving CsA treatment.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
Summary: Cryo-electron microscopy was used to study the structure of Na+, K+-ATPase and its variations. The results showed that different reaction states exhibited different biochemical characteristics, and the presence of Mg2+ ions in the transmembrane cation binding sites played a crucial role in the reactions. The binding mechanism of the new-generation cardiotonic steroids (CTSs) did not significantly affect the structure of NKA, and the phospholipid molecules were better resolved in the electron microscopy maps compared to X-ray structures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Haruo Ogawa, Kanna Motoyama, Bente Vilsen, Chikashi Toyoshima
Summary: The sodium pump (Na+, K+-ATPase, NKA) is crucial for maintaining ion gradients across cell membranes, with cardiotonic steroids (CTSs) acting as specific inhibitors. Different structural features of CTSs result in diverse inhibitory properties, with crystal structures providing insights into their mechanism of action and potential for isoform specific targeting.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Santiago E. Faraj, Wanda M. Valsecchi, Mariela Ferreira-Gomes, Mercedes Centeno, Elina Malen Saint Martin, Natalya U. Fedosova, Juan Pablo FC. Rossi, Monica R. Montes, Rolando C. Rossi
Summary: The Na+/K+-ATPase is a plasma membrane glycoprotein that exchanges intracellular Na+ for extracellular K+ by hydrolyzing ATP. The asymmetric distribution of Na+ and K+ is essential for cellular life. Current research indicates that Na+ becomes spontaneously occluded in the E1 dephosphorylated form of the Na+/K+-ATPase, showing positive interactions between binding sites. Adding ATP does not increase Na+ occlusion.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Cell Biology
Kelath Murali Manoj, Daniel A. A. Gideon, Nikolai M. M. Bazhin, Hirohisa Tamagawa, Vijay Nirusimhan, Mahendra Kavdia, Laurent Jaeken
Summary: The redox metabolic paradigm emphasizes the importance of diffusible reactive species (DRS), particularly oxygen-centric radicals, in physiology. This article focuses on the membrane protein Na,K-ATPase (NKA) and its role in neuro-cardio-musculo electrophysiology. Through analyzing diffusion, NKA's structural features, ion transport mechanisms, and inhibitory effects of various substances, a minimalist murburn model is proposed to explain the physiological inhibitory effects of different substances on cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Wei Chen, Lei Wang, Pengfei Liang, Jason Mast, Clausell Mathis, Catherine Y. Liu, Jin Wei, Jie Zhang, Liying Fu, Luis A. Juncos, Jacentha Buggs, Ruisheng Liu
Summary: This study demonstrates the potential therapeutic effect of using a synchronization modulation electric field to activate Na/K pumps and maintain cellular functions during renal ischemia-reperfusion injury.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A. S. Peres, Sarah A. S. Alves, Carolina Novaes-Fernandes, Wagner B. Dias, Ana Acacia S. Pinheiro, Diogo B. Peruchetti, Celso Caruso-Neves
Summary: This study identified that in the early stage of diabetes, tubular sodium reabsorption impairment is due to SGLT2-mediated high glucose influx in proximal tubule epithelial cells (PTECs), leading to an increase in O-GlcNAcylation and a reduction in the expression and activity of ATPase (NKA).
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Biochemistry & Molecular Biology
Ryuta Kanai, Bente Vilsen, Flemming Cornelius, Chikashi Toyoshima
Summary: Na+,K+-ATPase (NKA) plays a crucial role in establishing electrochemical gradients for Na+ and K+ across the cell membrane. This study presents two crystal structures of NKA in different states, providing insight into its reaction cycle and functional roles. The findings demonstrate how NKA converts between different forms and utilizes the lipid bilayer for gating the ion pathway.
Article
Biochemistry & Molecular Biology
Ryuta Kanai, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
Summary: In this study, the 3.3 angstrom resolution structure of Na+,K+-ATPase (NKA) in the E2·2K(+) state was resolved using cryo-electron microscopy. The transition from the E2P state to the E2·2K(+) state involves the closure and locking of the extracellular ion pathway, as well as events at the phosphorylation site over 50 angstrom away. Furthermore, the binding of ATP to NKA in the E2·2K(+) state was found to relax the gating machinery and greatly accelerate the release of K+ into the cytoplasm.
Review
Neurosciences
Kenneth T. MacLeod
Summary: The heart shows great phenotypic plasticity in adapting to disease and loss of tissue, but the long-term consequences can lead to heart failure and poor prognosis. Changes in ion channels and transporters compromise the efficiency of Ca2+ release from the sarcoplasmic reticulum and increase the likelihood of arrhythmias. These adaptations come at the expense of the heart's overall function and can activate hypertrophic and apoptotic pathways.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Plant Sciences
Muhammad Farooq, Jae-Ryoung Park, Yoon-Hee Jang, Eun-Gyeong Kim, Kyung-Min Kim
Summary: This study demonstrates that under salt stress, the Nagdong cultivar has better salt tolerance than the Cheongcheong cultivar, as evidenced by higher germination rate, plant vigor, Na+/K+ ratio, and expression of genes related to salt tolerance.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Medicine, Research & Experimental
Mi Seon Seo, Jin Ryeol An, Minji Kang, Ryeon Heo, Hongzoo Park, Eun-Taek Han, Jin-Hee Han, Wanjoo Chun, Won Sun Park
Summary: The study showed that canagliflozin induces vasodilation in rabbit aortic rings, dependent on robust SERCA activity and Kv channel activation.
Article
Neurosciences
Sandesh Mohan, Manindra Nath Tiwari, Marija Stanojevic, Yoav Biala, Yoel Yaari
Summary: Stimulation of muscarinic receptors on hippocampal neurons activates multiple signaling pathways that inhibit Na+/K+-ATPase activity, leading to increased intrinsic neuronal excitability through enhanced enzyme phosphorylation. This novel mechanism contributes to cholinergic modulation of hippocampal activity in spatial navigation, learning and memory.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Biochemistry & Molecular Biology
Anieli Cristina Maraschi, Samuel Coelho Faria, John Campbell McNamara
Summary: This study focused on the ion regulation capabilities of palaemonid shrimps in different salinity environments. Palaemonids exhibit hypo-regulation in high salinity and hyper-regulation in low salinity. The research revealed a positive correlation between the expression of gill NKCC protein and the hemolymph's hyper-osmoregulatory capacity, suggesting a role for NKCC in salt secretion.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kazuhiro Abe, Tomohiro Nishizawa, Pablo Artigas
Summary: The structures of NKA and ngHKA have similar features, but there are differences that contribute to their functional divergence. These pumps can switch between two conformations and differ in their transported substrates and stoichiometries. The structures of ngHKA mutants were found to be similar to NKA structures under specific conditions. This finding provides important insights into the molecular mechanism of E2-E1 transition and cooperative sodium binding.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Arvind Ponnusamy, Smeeta Sinha, Gareth D. Hyde, Samantha J. Borland, Rebecca F. Taylor, Emma Pond, Heather J. Eyre, Colette A. Inkson, Andrew Gilmore, Nick Ashton, Philip A. Kalra, Ann E. Canfield
Article
Medicine, Research & Experimental
Saleh H. Alwasel, David J. P. Barker, Nick Ashton
Article
Physiology
Ellen J. Forty, Nick Ashton
EXPERIMENTAL PHYSIOLOGY
(2012)
Article
Physiology
Saleh H. Alwasel, Vandana Sahajpal, Nick Ashton
KIDNEY & BLOOD PRESSURE RESEARCH
(2010)
Article
Pediatrics
Saleh H. Alwasel, Nick Ashton
PEDIATRIC NEPHROLOGY
(2012)
Article
Multidisciplinary Sciences
Corina Anders, Nick Ashton, Parisa Ranjzad, Mark R. Dilworth, Adrian S. Woolf
Article
Multidisciplinary Sciences
Ellen J. Forty, Nick Ashton
Article
Multidisciplinary Sciences
Gareth D. Hyde, Rebecca F. Taylor, Nick Ashton, Samantha J. Borland, Hon Sing Geoffrey Wu, Andrew P. Gilmore, Ann E. Canfield
Article
Physiology
Heather J. Eyre, Thomas Speight, Jocelyn D. Glazier, David M. Smith, Nick Ashton
EXPERIMENTAL PHYSIOLOGY
(2019)
Review
Obstetrics & Gynecology
Jocelyn D. Glazier, Dexter J. L. Hayes, Sabiha Hussain, Stephen W. D'Souza, Joanne Whitcombe, Alexander E. P. Heazell, Nick Ashton
BMC PREGNANCY AND CHILDBIRTH
(2018)
Article
Multidisciplinary Sciences
Mais Absi, Basma G. Eid, Nick Ashton, George Hart, Alison M. Gurney
Review
Biochemistry & Molecular Biology
Samantha J. Borland, Julia Behnsen, Nick Ashton, Sheila E. Francis, Keith Brennan, Michael J. Sherratt, Philip J. Withers, Ann E. Canfield
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Developmental Biology
Wejdan H. Owaydhah, Nick Ashton, Francois Verrey, Jocelyn D. Glazier
Summary: The study found that LAT1, LAT2, and LAT4 are all expressed in both rat placenta and yolk sac, suggesting a combined role for these LAT subtypes in supporting fetal growth and development.
Article
Multidisciplinary Sciences
Alaa Alkhalefah, Heather J. Eyre, Rezwana Hussain, Jocelyn D. Glazier, Nick Ashton
Summary: In a rat model study, it was found that maternal intermittent fasting does not affect cardiovascular, metabolic, and renal function in adult offspring, but male offspring are more prone to renal injury when challenged with a dietary salt load.
Article
Biochemistry & Molecular Biology
Malgorzata M. Michalowska, Karl Herholz, Rainer Hinz, Chinenye Amadi, Lynn McInnes, Jose M. Anton-Rodriguez, Thomas K. Karikari, Kaj Blennow, Henrik Zetterberg, Nicholas J. Ashton, Neil Pendleton, Stephen F. Carter
Summary: This study investigated the distribution of amyloid-beta (A ss) and evaluated different in vivo amyloid-PET staging schemes in elderly individuals. The findings suggest that early amyloid stages cannot be consistently classified and that the majority of the cohort had pathological A ss. The study highlights the need to determine what constitutes abnormal brain A ss in the oldest-old and the best method to determine that.
MOLECULAR PSYCHIATRY
(2022)