{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:37:08Z","timestamp":1760549828213},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T00:00:00Z","timestamp":1441929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ionophore antibiotic nonactin permeabilizes cell membranes to <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/bcpt12455-math-0001.png\" xlink:title=\"urn:x-wiley:17427835:media:bcpt12455:bcpt12455-math-0001\" \/> and K<jats:sup>+<\/jats:sup>. Treatment of erythrocytes with nonactin is expected to trigger cellular K<jats:sup>+<\/jats:sup> loss with subsequent cell shrinkage, which in turn is known to trigger suicidal death of a wide variety of cells including erythrocytes. This study explored whether nonactin exposure induces eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signalling of eryptosis includes increase in cytosolic Ca<jats:sup>2+<\/jats:sup> activity [(Ca<jats:sup>2+<\/jats:sup>)<jats:sub>i<\/jats:sub>] and stimulation of protein kinase C (<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>) as well as p38 mitogen\u2010activated protein kinase. Phosphatidylserine abundance at the cell surface was estimated from annexin\u2010V\u2010binding, cell volume from forward scatter (FSC) and (Ca<jats:sup>2+<\/jats:sup>)<jats:sub>i<\/jats:sub> from Fluo3\u2010fluorescence. A 48\u2010hr treatment of human erythrocytes with nonactin significantly decreased FSC (\u226510\u00a0ng\/ml) and significantly increased the percentage of annexin\u2010V\u2010binding cells (\u226510\u00a0ng\/ml), effects paralleled by increase in (Ca<jats:sup>2+<\/jats:sup>)<jats:sub>i<\/jats:sub> (\u226550\u00a0ng\/ml) and virtually abrogated by increase in extracellular K<jats:sup>+<\/jats:sup> concentration to 120\u00a0mM at the expense of Na<jats:sup>+<\/jats:sup>. The up\u2010regulation of annexin\u2010V\u2010binding after nonactin treatment was significantly blunted but not abolished by the removal of extracellular Ca<jats:sup>2+<\/jats:sup> and by addition of either <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> inhibitor staurosporine (0.4\u00a0\u03bcM) or p38 kinase inhibitor <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580 (2\u00a0\u03bcM). In conclusion, exposure of erythrocytes to the K<jats:sup>+<\/jats:sup> ionophore nonactin induces erythrocyte shrinkage and subsequent erythrocyte membrane scrambling, effects involving cellular K<jats:sup>+<\/jats:sup> loss, Ca<jats:sup>2+<\/jats:sup> entry and activation of staurosporine as well as <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580\u2010sensitive kinases.<\/jats:p>","DOI":"10.1111\/bcpt.12455","type":"journal-article","created":{"date-parts":[[2015,8,17]],"date-time":"2015-08-17T15:35:30Z","timestamp":1439825730000},"page":"107-112","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Erythrocyte Shrinkage and Cell Membrane Scrambling after Exposure to the Ionophore Nonactin"],"prefix":"10.1111","volume":"118","author":[{"given":"Thomas","family":"Peter","sequence":"first","affiliation":[{"name":"Department of Physiology University of Tuebingen Tuebingen 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