Article
Biochemistry & Molecular Biology
Marlene U. Fruergaard, Ingrid Dach, Jacob L. Andersen, Mette Ozol, Azadeh Shahsavar, Esben M. Quistgaard, Hanne Poulsen, Natalya U. Fedosova, Poul Nissen
Summary: In this study, the crystal structure and functional properties of the E2-BeFx complex of pig kidney Na+,K+-ATPase are investigated. The complex resembles the E2P intermediate and is able to bind ADP/ATP and Na+. The results suggest a relation between E2-BeFx and the E*P intermediate in the functional cycle of Na+, K+-ATPase.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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
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)
Article
Biochemistry & Molecular Biology
Violetta V. Kravtsova, Arina A. Fedorova, Maria Tishkova, Alexandra A. Livanova, Oleg V. Vetrovoy, Alexander G. Markov, Vladimir V. Matchkov, Igor I. Krivoi
Summary: This study investigated the protective effect of ouabain on ionizing radiation-induced disturbances in skeletal muscle Na,K-ATPase function. Ouabain was found to prevent depolarization and loss of electrogenic contribution of the alpha 2 isozyme of Na,K-ATPase, accompanied by an increase in circulating ouabain concentration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Violetta V. Kravtsova, Arina A. Fedorova, Maria Tishkova, Alexandra A. Livanova, Viacheslav O. Matytsin, Viacheslav P. Ganapolsky, Oleg V. Vetrovoy, Igor I. Krivoi
Summary: The Na,K-ATPase plays a crucial role in adaptation to hypoxia, and hypoxic preconditioning can protect against functional impairments. Mild hypoxia was found to modulate the Na,K-ATPase and improve skeletal muscle electrogenesis, which may have implications for countermeasures in disuse-induced pathology and hypoxic therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Song Jiao, Kory Johnson, Cristina Moreno, Sho Yano, Miguel Holmgren
Summary: Research indicates that Na+/K+-ATPase α1 and α3 subunits are enriched in specific neuronal populations in the brain, with α3-expressing neurons playing a crucial role in cerebellar neuronal circuits. Furthermore, co-expression network analysis reveals key genes positively correlated with the expression of Na+/K+-ATPase α1 and α3.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
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
Biochemistry & Molecular Biology
Violetta V. Kravtsova, Inna I. Paramonova, Natalia A. Vilchinskaya, Maria V. Tishkova, Vladimir V. Matchkov, Boris S. Shenkman, Igor I. Krivoi
Summary: This study investigated the effects of ouabain on skeletal muscle electrophysiology and membrane depolarization. It was found that chronic administration of ouabain partially prevented membrane depolarization in skeletal muscle, potentially through the IL-6/AMPK pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Mrudhula Sajeevadathan, Murray J. Pettitt, Mary M. Buhr
Summary: The study suggests the existence of rafts in the HPM of bull sperm, with Na+K+-ATPase subunit isoforms preferentially localized there. Analysis of the Western blot profiles showed that alpha 3 and beta 1 were relatively dominant isoforms in the HPM raft, hinting at unique sequences within the isoform structure for capacitation signaling.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Ivan Kushkevych, Mykola Bychkov, Solomiia Bychkova, Mario Gajdacs, Romana Merza, Monika Vitezova
Summary: Autophagy allows prolonged survival in tumor cells with defects in apoptosis, and NAADP may affect the release of Ca2+ from organelles. The activity of ATPases in colorectal cancer tissues is higher, and NAADP has different effects on ion transport in cancer and control samples, showing promising possibilities for the treatment of colorectal cancer.
Article
Plant Sciences
Magda F. El-Adl, Taha M. El-Katony, Reham M. Nada
Summary: The study found that the specific ion effects of Na+ and K+ were different on the growth of Ulva lactuca. Ulva lactuca showed better growth with high concentrations of NaCl, while KCl might have adverse effects on photosynthesis and cell wall. Transcription of PM H+-ATPase was induced specifically by high concentrations of Na+, while the induction of PM-Na+/K+-ATPase-like alone could not improve the growth of KCl-treated Ulva lactuca.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
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.
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.
Review
Cell Biology
Deborah Rotoli, Lucio Diaz-Flores, Ricardo Gutierrez, Manuel Morales, Julio Avila, Pablo Martin-Vasallo
Summary: Glioma stem cells (GSCs) undergo continuous stemness reprogramming within specific GSC niches, with scaffold proteins playing an important role in this process and potentially impacting the treatment and prognosis of glioblastoma.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2022)
Article
Orthopedics
Ari Vaarala, Victor Casula, Arttu Peuna, Egor Panfilov, Ali Mobasheri, Marianne Haapea, Eveliina Lammentausta, Miika T. Nieminen
Summary: In this study, a 3D texture analysis method based on gray level co-occurrence matrix was developed for knee cartilage analysis in osteoarthritis studies. The method was able to detect longitudinal changes in cartilage and distinguish different subpopulations based on their progression into radiographically confirmed osteoarthritis. The results showed significant changes in textural features of femoral and tibial cartilages across all groups and tissue layers.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Review
Rheumatology
Vera Francisco, Jesus Pino, Miguel Angel Gonzalez-Gay, Francisca Lago, Jaro Karppinen, Osmo Tervonen, Ali Mobasheri, Oreste Gualillo
Summary: Studies have found that immunometabolic alterations in patients with obesity and type 2 diabetes mellitus are closely related to intervertebral disc degeneration, involving the abnormal production of proteins such as adipokines and exacerbation of inflammatory responses.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Cell & Tissue Engineering
Ignacio Dallo, Riccardo D'Ambrosi, Dawid Szwedowski, Ali Mobasheri, Alberto Gobbi
Summary: Bone marrow lesions (BMLs) are common findings in different knee pathologies, but the etiology and treatment protocol for symptomatic BMLs remain unclear. This study evaluates the clinical outcomes and safety of Osteo Core Plasty technique in treating symptomatic BMLs in the knee, and it shows promising results in reducing pain and improving overall scores.
STEM CELLS AND DEVELOPMENT
(2022)
Review
Orthopedics
Ursule Kalvaityte, Csaba Matta, Eiva Bernotiene, Peter Natesan Pushparaj, Ata M. Kiapour, Ali Mobasheri
Summary: This article reviews the biological roles of clusterin in cartilage, chondrocytes, and other synovial joint tissues, and discusses its potential as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Clusterin has cytoprotective functions and may serve as a biomarker of early repair responses in OA.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2022)
Article
Rheumatology
Federico Angelini, Pawel Widera, Ali Mobasheri, Joseph Blair, Andre Struglics, Melanie Uebelhoer, Yves Henrotin, Anne Ca Marijnissen, Margreet Kloppenburg, Francisco J. Blanco, Ida K. Haugen, Francis Berenbaum, Christoph Ladel, Jonathan Larkin, Anne C. Bay-Jensen, Jaume Bacardit
Summary: The study found three dominant endotypes associated with three phenotypes: low tissue turnover, structural damage, and systemic inflammation. Each endotype presented different disease characteristics, indicating the potential for personalized treatment strategies in the future.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Cell Biology
Rebeca Gonzalez-Fernandez, Maria Angeles Gonzalez-Nicolas, Manuel Morales, Julio Avila, Alberto Lazaro, Pablo Martin-Vasallo
Summary: The study suggests that FKBP51, AmotL2, and IQGAP1 are overexpressed in various types of cancer, with the highest increase observed in leucocytes from patients undergoing oxaliplatin chemotherapy. Microscopic examination of renal tissue indicates these proteins may play a role in the development of cisplatin toxicity in kidney tubules.
Article
Biochemistry & Molecular Biology
Manuel Morales, Pablo Martin-Vasallo, Julio Avila
Summary: Enzalutamide treatment may increase the risk of cardiovascular-related hospitalization in patients, potentially due to MR gene polymorphism, suggesting the importance of evaluating MR rs5522 polymorphism before starting AR inhibitor therapy.
Article
Biochemistry & Molecular Biology
Dawid Szwedowski, Ali Mobasheri, Andrzej Moniuszko, Jan Zabrzynski, Slawomir Jeka
Summary: In patients with knee osteoarthritis, it was found that those receiving PRP treatment showed significant functional improvement within 6 months, which was superior to treatment with HA or CS; in terms of pain reduction, the CS group performed the best, but the effect decreased gradually in subsequent visits.
Article
Clinical Neurology
Ali Mobasheri
Summary: The concept of self-healing through integrative medicine and natural remedies is introduced as a new approach to managing musculoskeletal conditions. This approach highlights the potential for improving patient outcomes by optimizing the body's innate ability to heal itself.
JOURNAL OF PAIN RESEARCH
(2022)
Review
Cell Biology
Csaba Matta, Roland Takacs, Laszlo Ducza, Rana Abdelsattar Ebeid, Heonsik Choi, Ali Mobasheri
Summary: Osteoarthritis (OA) is a chronic, progressive, and debilitating musculoskeletal condition with chronic pain as one of its main symptoms. The true source of OA pain is still unclear, despite ongoing research into its pathomechanisms. Ion channels and transporters play a key role in nociceptive pain, and this review article provides an update on their distribution and function in synovial joint tissues. It also proposes directions for the development of future analgesic therapies for OA pain.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ilona Uzieliene, Daiva Bironaite, Rokas Miksiunas, Edvardas Bagdonas, Raminta Vaiciuleviciute, Ali Mobasheri, Eiva Bernotiene
Summary: This study investigated the role of intracellular calcium (iCa(2+)) and its regulation through voltage-operated calcium channels (VOCC) in the chondrogenic differentiation of mesenchymal stem/stromal cells. Results showed that chondrocytes had the highest level of iCa(2+), while MenSCs had the largest iCa(2+) store capacity and proliferation ability. The expression of the CaV1.2 gene was highest in MenSCs during chondrogenic differentiation. Nifedipine, a CaV1.2 antagonist, could suppress iCa(2+) and proliferation in all cells and affect iCa(2+) stores, especially in BMMSCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mohammad Mehdi Ommati, Ali Mobasheri, Hossein Niknahad, Mohammad Rezaei, Sepideh Alidaee, Abdollah Arjmand, Sahra Mazloomi, Narges Abdoli, Issa Sadeghian, Samira Sabouri, Mohsen Saeed, Khadijeh Mousavi, Asma Najibi, Reza Heidari
Summary: Ammonium ion (NH4+) is suspected to be the main molecule responsible for neurological complications in hepatic encephalopathy. This study investigated the effects of the NMDA receptor antagonist ketamine on hyperammonemic mice and found that it significantly improved locomotor activity, biomarkers of oxidative stress, and decreased proinflammatory cytokines. These findings suggest that ketamine may have neuroprotective mechanisms against NH4+-induced neurotoxicity.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
