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In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1\/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1\/2 (<jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) and corresponding wild-type mice (<jats:italic>msk<\/jats:italic><jats:sup>+\/+<\/jats:sup>). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>msk<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice, but reticulocyte count was significantly increased in <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Cell membrane PS exposure was similar in untreated <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>msk<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes, but was enhanced by pathophysiological cell stressors <jats:italic>ex vivo<\/jats:italic> such as hyperosmotic shock or energy depletion to significantly higher levels in <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes than in <jats:italic>msk<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes. The <jats:italic>in vivo<\/jats:italic> clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. The spleens from <jats:italic>msk<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice contained a significantly greater number of PS-exposing erythrocytes than spleens from <jats:italic>msk<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1\/2-deficient mice.<\/jats:p>","DOI":"10.1038\/srep17316","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T09:37:22Z","timestamp":1448617042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1\/2"],"prefix":"10.1038","volume":"5","author":[{"given":"Elisabeth","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosi","family":"Bissinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul","family":"Fajol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri S.","family":"Salker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Zelenak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Ghashghaeinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchen","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Jilani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Lupescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M. 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