{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:09:57Z","timestamp":1782122997408,"version":"3.54.5"},"reference-count":95,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T00:00:00Z","timestamp":1703376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"St. Petersburg State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ionizing radiation (IR) causes disturbances in the functions of the gastrointestinal tract. Given the therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against IR-induced disturbances in the barrier and transport properties of the jejunum and colon of rats. Male Wistar rats were subjected to 6-day intraperitoneal injections of vehicle or ouabain (1 \u00b5g\/kg\/day). On the fourth day of injections, rats were exposed to total-body X-ray irradiation (10 Gy) or a sham irradiation. Isolated tissues were examined 72 h post-irradiation. Electrophysiological characteristics and paracellular permeability for sodium fluorescein were measured in an Ussing chamber. Histological analysis and Western blotting were also performed. In the jejunum tissue, ouabain exposure did not prevent disturbances in transepithelial resistance, paracellular permeability, histological characteristics, as well as changes in the expression of claudin-1, -3, -4, tricellulin, and caspase-3 induced by IR. However, ouabain prevented overexpression of occludin and the pore-forming claudin-2. In the colon tissue, ouabain prevented electrophysiological disturbances and claudin-2 overexpression. These observations may reveal a mechanism by which circulating ouabain maintains tight junction integrity under IR-induced intestinal dysfunction.<\/jats:p>","DOI":"10.3390\/ijms25010278","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:44:15Z","timestamp":1703450655000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier"],"prefix":"10.3390","volume":"25","author":[{"given":"Alexander G.","family":"Markov","sequence":"first","affiliation":[{"name":"Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra A.","family":"Livanova","sequence":"additional","affiliation":[{"name":"Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina A.","family":"Fedorova","sequence":"additional","affiliation":[{"name":"Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta V.","family":"Kravtsova","sequence":"additional","affiliation":[{"name":"Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-9226","authenticated-orcid":false,"given":"Igor I.","family":"Krivoi","sequence":"additional","affiliation":[{"name":"Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3748\/wjg.v19.i2.185","article-title":"Gastrointestinal radiation injury: Symptoms, risk factors and mechanisms","volume":"19","author":"Shadad","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.3109\/10715762.2015.1071485","article-title":"Protective effect of sesamol against \u2076\u2070Co \u03b3-ray-induced hematopoietic and gastrointestinal injury in C57BL\/6 male mice","volume":"49","author":"Khan","year":"2015","journal-title":"Free Radic. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/02841860310010826","article-title":"The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001\u2014Summary and conclusions","volume":"42","author":"Ringborg","year":"2003","journal-title":"Acta Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.lssr.2014.02.004","article-title":"Biological effects of space radiation and development of effective countermeasures","volume":"1","author":"Kennedy","year":"2014","journal-title":"Life Sci. Space Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"360","DOI":"10.2307\/3578835","article-title":"Peripheral Blood Corticotropin-Releasing Factor, Adrenocorticotropic Hormone and Cytokine (Interleukin Beta, Interleukin 6, Tumor Necrosis Factor Alpha) Levels after High- and Low-Dose Total-Body Irradiation in Humans","volume":"139","author":"Girinsky","year":"1994","journal-title":"Rad. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13014-016-0752-1","article-title":"Intraoperative radiation therapy for colon and rectal cancers: A clinical review","volume":"12","author":"Haddock","year":"2017","journal-title":"Radiat Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/HP.0000000000000066","article-title":"Increased occupational radiation doses: Nuclear fuel cycle","volume":"106","author":"Bouville","year":"2014","journal-title":"Health Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/0016-5085(88)90512-4","article-title":"Prospects for management of gastrointestinal injury associated with the acute radiation syndrome","volume":"95","author":"Dubois","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.rpor.2011.06.001","article-title":"Radiobiology of the acute radiation syndrome","volume":"16","author":"Garau","year":"2011","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_10","first-page":"L647","article-title":"Structure, function, and regulation of cellular tight junctions","volume":"262","author":"Schneeberger","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tibs.2018.09.008","article-title":"The Claudins: From Tight Junctions to Biological Systems","volume":"44","author":"Tsukita","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1748-1716.2010.02148.x","article-title":"Claudins of intestine and nephron\u2014A correlation of molecular tight junction structure and barrier function","volume":"201","author":"Amasheh","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fphys.2014.00221","article-title":"Tight junction physiology of pleural mesothelium","volume":"5","author":"Markov","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109485","DOI":"10.1016\/j.cellsig.2019.109485","article-title":"Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease","volume":"66","author":"Cong","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1242\/jcs.00165","article-title":"Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells","volume":"115","author":"Amasheh","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1242\/jcs.060665","article-title":"Claudin-2, a component of the tight junction, forms a paracellular water channel","volume":"123","author":"Rosenthal","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/apha.12742","article-title":"Claudin-2-mediated cation and water transport share a common pore","volume":"219","author":"Rosenthal","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e977176","DOI":"10.4161\/21688370.2014.977176","article-title":"Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation","volume":"3","author":"Luettig","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s00424-019-02294-z","article-title":"Cholera toxin induces an increase of claudin-2 in the small intestinal epithelium of rats","volume":"471","author":"Markov","year":"2019","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1091\/mbc.e09-01-0080","article-title":"Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability","volume":"20","author":"Krug","year":"2009","journal-title":"Mol. Biol. Cell."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1091\/mbc.e09-08-0734","article-title":"Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions","volume":"21","author":"Raleigh","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e14960","DOI":"10.14814\/phy2.14960","article-title":"Dose and time dependence of functional impairments in rat jejunum following ionizing radiation exposure","volume":"9","author":"Livanova","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Livanova, A.A., Fedorova, A.A., Zavirsky, A.V., Krivoi, I.I., and Markov, A.G. (2023). Dose- and Segment-Dependent Disturbance of Rat Gut by Ionizing Radiation: Impact of Tight Junction Proteins. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021753"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbrc.2014.11.084","article-title":"Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure","volume":"456","author":"Shim","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"G705","DOI":"10.1152\/ajpgi.00314.2015","article-title":"Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: Protection by N-acetyl-l-cysteine","volume":"310","author":"Shukla","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1667\/RR14157.1","article-title":"Segmental Differences in Radiation-Induced Alterations of Tight Junction-Related Proteins in Non-Human Primate Jejunum, Ileum and Colon","volume":"185","author":"Garg","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13953","DOI":"10.1038\/s41598-019-49437-x","article-title":"C\/EBP\u03b4 protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress","volume":"9","author":"Banerjee","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00360-009-0440-7","article-title":"Segmental expression of claudin proteins correlates with tight junction barrier properties in rat intestine","volume":"180","author":"Markov","year":"2010","journal-title":"J. Comp. Physiol. B Biochem. Syst. Environ. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hamilton, K.L., and Devor, D.C. (2016). Ion Channels and Transporters of Epithelia in Health and Disease, Springer.","DOI":"10.1007\/978-1-4939-3366-2"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11387","DOI":"10.1073\/pnas.1000500107","article-title":"Ouabain modulates epithelial cell tight junction","volume":"107","author":"Larre","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2015.02.004","article-title":"Cardiotonic steroid ouabain stimulates expression of blood\u2013testis barrier proteins claudin-1 and -11 and formation of tight junctions in Sertoli cells","volume":"405","author":"Dietze","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.yexcr.2017.04.001","article-title":"Ouabain promotes partial epithelial to mesenchymal transition (EMT) changes in human autosomal dominant polycystic kidney disease (ADPKD) cells","volume":"355","author":"Venugopal","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Markov, A.G., Fedorova, A.A., Kravtsova, V.V., Bikmurzina, A.E., Okorokova, L.S., Matchkov, V.V., Cornelius, V., Amasheh, S., and Krivoi, I.I. (2020). Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145067"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2256146","DOI":"10.1080\/27694127.2023.2256146","article-title":"Ouabain promotes claudin-1, -2, and -4 autophagic degradation through oxidative stress and AMPK activation in MDCK cells","volume":"2","author":"Gallardo","year":"2023","journal-title":"Autophagy Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1073\/pnas.88.14.6259","article-title":"Identification and characterization of a ouabain-like compound from human plasma","volume":"88","author":"Hamlyn","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102159","DOI":"10.1016\/j.ceca.2020.102159","article-title":"Ouabain, endogenous ouabain and ouabain-like factors: The Na+ pump\/ouabain receptor, its linkage to NCX, and its myriad functions","volume":"86","author":"Blaustein","year":"2020","journal-title":"Cell Calcium."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1124\/pr.108.000711","article-title":"Endogenous cardiotonic steroids: Physiology, pharmacology, and novel therapeutic targets","volume":"61","author":"Bagrov","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3389\/fphys.2016.00179","article-title":"Specialized functional diversity and interactions of the Na,K-ATPase","volume":"7","author":"Matchkov","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lichtstein, D., Ilani, A., Rosen, H., Horesh, N., Singh, S.V., Buzaglo, N., and Hodes, A. (2018). Na+,K+-ATPase Signaling and Bipolar Disorder. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082314"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"824907","DOI":"10.3389\/fphar.2022.824907","article-title":"Neuroinflammation and Neutrophils: Modulation by Ouabain","volume":"13","author":"Leite","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"684316","DOI":"10.3389\/fonc.2021.684316","article-title":"Cardiac Glycoside Ouabain Exerts Anticancer Activity via Downregulation of STAT3","volume":"11","author":"Du","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16200","DOI":"10.1038\/s41598-020-72879-7","article-title":"Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19","volume":"10","author":"Cho","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.12659\/MSM.908627","article-title":"Ouabain protects mice against lipopolysaccharide-induced acute lung injury","volume":"24","author":"Wang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0014-5793(94)01067-6","article-title":"Inactivation of the Na,K-ATPase by radiation-induced free radicals. Evidence for a radical-chain mechanism","volume":"353","author":"Hitschke","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13969","DOI":"10.14814\/phy2.13969","article-title":"Alteration of renal Na,K-ATPase in rats following the mediastinal \u03b3-irradiation","volume":"7","author":"Janega","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kravtsova, V.V., Fedorova, A.A., Tishkova, M.V., Livanova, A.A., Vetrovoy, O.V., Markov, A.G., Matchkov, V.V., and Krivoi, I.I. (2022). Chronic Ouabain Prevents Radiation-Induced Reduction in the \u03b12 Na,K-ATPase Function in the Rat Diaphragm Muscle. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810921"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"682614","DOI":"10.3389\/fphar.2021.682614","article-title":"Claudins: Beyond Tight Junctions in Human IBD and Murine Models","volume":"12","author":"Musladin","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1089\/neu.2014.3544","article-title":"Ouabain improves functional recovery following traumatic brain injury","volume":"31","author":"Ami","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1002\/jcb.27693","article-title":"Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide-induced hypocampal neuroinflammation in rats","volume":"120","author":"Garcia","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0079-6603(08)60611-X","article-title":"DNA damage produced by ionizing radiation in mammalian cells: Identities, mechanisms of formation, and reparability","volume":"35","author":"Ward","year":"1988","journal-title":"Prog. Nucleic. Acid Res. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2119132119","DOI":"10.1073\/pnas.2119132119","article-title":"Formation of clustered DNA damage in vivo upon irradiation with ionizing radiation: Visualization and analysis with atomic force microscopy","volume":"119","author":"Nakano","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kim, W., Lee, S., Seo, D., Kim, D., Kim, K., Kim, E., Kang, J., Seong, K.M., Youn, H., and Youn, B. (2019). Cellular Stress Responses in Radiotherapy. Cells, 8.","DOI":"10.3390\/cells8091105"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1089\/scd.2014.0402","article-title":"Catalase inhibits ionizing radiation-induced apoptosis in hema-topoietic stem and progenitor cells","volume":"24","author":"Xiao","year":"2015","journal-title":"Stem Cells Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/imr.12572","article-title":"Immunomodulation by ionizing radiation-impact for design of radio-immunotherapies and for treatment of inflammatory diseases","volume":"280","author":"Frey","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1667\/0033-7587(2003)159[0471:TCMAAB]2.0.CO;2","article-title":"The cell membrane as a biosensor of oxidative stress induced by radiation exposure: A multiparameter investigation","volume":"159","author":"Benderitter","year":"2003","journal-title":"Radiat. Res."},{"key":"ref_57","first-page":"193","article-title":"Effects of Low-Dose X-ray on Oxidative State, Lipid Peroxidation, and Membrane Fluidity of Human Peripheral Blood Mononucleated Cells","volume":"52","author":"Pochano","year":"2019","journal-title":"J. Associat. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0300-483X(03)00149-5","article-title":"Protection against ionizing radiation by antioxidant nutrients and phytochemicals","volume":"189","author":"Weiss","year":"2003","journal-title":"Toxicology"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kumar, A., Kumarchandra, R., Rai, R., and Kumblekar, V. (2020). Radiation mitigating activities of Psidium guajava L. against whole-body X-ray-induced damages in albino Wistar rat model. 3 Biotech, 10.","DOI":"10.1007\/s13205-020-02484-y"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.freeradbiomed.2017.04.029","article-title":"Akt1\/NF\u03baB signaling pathway activation by a small molecule DMA confers radioprotection to intestinal epithelium in xenograft model","volume":"108","author":"Tiwari","year":"2017","journal-title":"Free Radic Biol Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hellweg, C.E., Spitta, L.F., Koch, K., Chishti, A.A., Henschenmacher, B., Diegeler, S., Konda, B., Feles, S., Schmitz, C., and Berger, T. (2018). The Role of the Nuclear Factor \u03baB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082220"},{"key":"ref_62","first-page":"F633","article-title":"Isozymes of the Na-K-ATPase: Heterogeneity in structure, diversity in function","volume":"275","author":"Blanco","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3389\/fphys.2017.00371","article-title":"The structure and function of the Na,K-ATPase isoforms in health and disease","volume":"8","author":"Clausen","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-physiol-021909-135725","article-title":"The physiological significance of the cardiotonic steroid\/ouabain-binding site of the Na,K-ATPase","volume":"72","author":"Lingrel","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1046\/j.1432-1033.2002.02911.x","article-title":"Endogenous cardiac glycosides, a new class of steroid hormones","volume":"269","author":"Schoner","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1161\/01.HYP.0000165024.47728.f7","article-title":"Ouabain-Like compound changes rapidly on physical exercise in humans and dogs: Effects of \u03b2-blockade and angiotensin-converting enzyme inhibition","volume":"45","author":"Bauer","year":"2005","journal-title":"Hypertension"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Khalaf, F.K., Dube, P., Mohamed, A., Tian, J., Malhotra, D., Haller, S.T., and Kennedy, D.J. (2018). Cardiotonic steroids and the sodium trade balance: New insights into trade-off mechanisms mediated by the Na+\/K+-ATPase. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092576"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kravtsova, V.V., Fedorova, A.A., Tishkova, M.V., Livanova, A.A., Matytsin, V.O., Ganapolsky, V.P., Vetrovoy, O.V., and Krivoi, I.I. (2022). Short-Term Mild Hypoxia Modulates Na,K-ATPase to Maintain Membrane Electrogenesis in Rat Skeletal Muscle. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911869"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fphys.2016.00107","article-title":"Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway","volume":"7","author":"Venugopal","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.redox.2014.12.015","article-title":"Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump\u2019s activity","volume":"4","author":"Omotayo","year":"2015","journal-title":"Redox Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"F77","DOI":"10.1152\/ajprenal.00581.2009","article-title":"Ouabain stimulates Na-K-ATPase through a sodium\/hydrogen exchanger-1 (NHE-1)-dependent mechanism in human kidney proximal tubule cells","volume":"299","author":"Holthouser","year":"2010","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1161\/01.HYP.0000027134.14160.1D","article-title":"Ouabain-binding protein(s) from human plasma","volume":"40","author":"Haberly","year":"2002","journal-title":"Hypertension"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/01.CIR.45.6.1176","article-title":"Ouabain pharmacokinetics in dog and man. Determination by radioimmunoassay","volume":"45","author":"Selden","year":"1972","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102151","DOI":"10.1016\/j.ceca.2019.102151","article-title":"Sodium pumps, ouabain and aldosterone in the brain: A neuromodulatory pathway underlying salt-sensitive hypertension and heart failure","volume":"86","author":"Leenen","year":"2020","journal-title":"Cell Calcium"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1667\/RR3180","article-title":"Differential qualitative and temporal changes in the response of the hypothalamus-pituitary-adrenal axis in rats after localized or total-body irradiation","volume":"161","author":"Wysocki","year":"2004","journal-title":"Radiat. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/labinvest.2008.78","article-title":"Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation","volume":"88","author":"Weber","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2147\/JIR.S275595","article-title":"Reactive Oxygen Species: Drivers of Physiological and Pathological Processes","volume":"13","author":"Checa","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s12094-017-1828-6","article-title":"Reduction-oxidation (redox) system in radiation-induced normal tissue injury: Molecular mechanisms and implications in radiation therapeutics","volume":"20","author":"Yahyapour","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/09629359791677","article-title":"Ionizing radiation enhances IL-6 and IL-8 production by human endothelial cells","volume":"6","author":"Meeren","year":"1997","journal-title":"Mediat. Inflamm."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00441-009-0751-8","article-title":"TNFalpha up-regulates claudin-2 expression in epithelial HT-29\/B6 cells via phosphatidylinositol-3-kinase signaling","volume":"336","author":"Mankertz","year":"2009","journal-title":"Cell Tissue Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1242\/jcs.070896","article-title":"TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NF-kappaB signaling","volume":"123","author":"Amasheh","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1038\/s41598-017-04989-8","article-title":"Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin Switching","volume":"7","author":"Ahmad","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"31263","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1038\/s41598-019-41442-4","article-title":"Caveolin 1 is Associated with Upregulated Claudin 2 in Necrotizing Enterocolitis","volume":"9","author":"Ares","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Dalton, C.M., Schlegel, C., and Hunter, C.J. (2023). Caveolin-1: A Review of Intracellular Functions, Tissue-Specific Roles, and Epithelial Tight Junction Regulation. Biology, 12.","DOI":"10.3390\/biology12111402"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1015500","DOI":"10.3389\/fphys.2022.1015500","article-title":"Role of AMPK in autophagy","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41401-019-0290-0","article-title":"Ouabain impairs cancer metabolism and activates AMPK-Src signaling pathway in human cancer cell lines","volume":"41","author":"Shen","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.semcdb.2023.03.008","article-title":"The emerging roles of the cytoskeleton in intestinal epithelium homeostasis","volume":"150\u2013151","author":"Perrin","year":"2023","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Guan, G., Cannon, R.D., Coates, D.E., and Mei, L. (2023). Effect of the Rho-Kinase\/ROCK Signaling Pathway on Cytoskeleton Components. Genes, 14.","DOI":"10.3390\/genes14020272"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.3390\/cimb45090475","article-title":"Ouabain Induces Transcript Changes and Activation of RhoA\/ROCK Signaling in Cultured Epithelial Cells (MDCK)","volume":"45","author":"Hinojosa","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Feng, S., Zou, L., Wang, H., He, R., Liu, K., and Zhu, H. (2018). RhoA\/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier Permeability. Molecules, 23.","DOI":"10.3390\/molecules23092371"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19582","DOI":"10.1074\/jbc.M110.119248","article-title":"Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase","volume":"285","author":"Katz","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"C126","DOI":"10.1152\/ajpcell.00089.2015","article-title":"Cardiac glycosides induced toxicity in human cells expressing \u03b11-, \u03b12-, or \u03b13-isoforms of Na-K-ATPase","volume":"309","author":"Karlish","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_95","unstructured":"(2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [8th ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:17Z","timestamp":1760132477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,24]]},"references-count":95,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010278"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010278","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,24]]}}}