{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T19:10:02Z","timestamp":1771960202906,"version":"3.50.1"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016263","name":"University Research Board, American University of Beirut","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016263","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Cisplatin is a chemotherapeutic agent that reverts cancerous cells to the apoptotic route. A decrease in the activity of the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    ATPase is one of the hallmarks of apoptosis and a major causative factor of the drug-induced nephrotoxicity. Whether cisplatin targets also the colonic ATPase is a question that was addressed in this work using Caco-2 cells as a model. ATPase activity was measured via inorganic phosphate release with and without ouabain, and protein expression was assessed by Western blot. Cisplatin reduced the activity of the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    ATPase, an effect that was dependent on the transmembrane chloride gradient but had no effect on the purified enzyme, suggesting an indirect action. Fluorescence imaging showed a decrease in the membrane ATPase abundance. Cisplatin was shown to act by increasing intracellular calcium, triggering a sequential activation of p38MAPK and PKA that results in JNK inhibition and a decrease in the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    ATPase activity.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0342707","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T18:34:16Z","timestamp":1771958056000},"page":"e0342707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of action of cisplatin on Na+\/K+ ATPase of Caco-2 colon cells in vitro"],"prefix":"10.1371","volume":"21","author":[{"given":"Rida","family":"Mourad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawad","family":"Hodeify","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-4081","authenticated-orcid":true,"given":"Sawsan","family":"Kreydiyyeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"pone.0342707.ref001","doi-asserted-by":"crossref","first-page":"106939","DOI":"10.1016\/j.ejps.2024.106939","article-title":"Advances in understanding cisplatin-induced toxicity: Molecular mechanisms and protective strategies","volume":"203","author":"EA Elmorsy","year":"2024","journal-title":"Eur J Pharm 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