Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

Elisabeth Lang, Rosi Bissinger, Abul Fajol, Madhuri S. Salker, Yogesh Singh, Christine Zelenak, Mehrdad Ghashghaeinia, Shuchen Gu, Kashif Jilani, Adrian Lupescu, Kathleen M. S. E. Reyskens, Teresa F. Ackermann, Michael Föller, Erwin Schleicher, William P. Sheffield, J. Simon C. Arthur, Florian Lang (Lead / Corresponding author), Syed M. Qadri

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    The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. 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 (msk(-/-)) and corresponding wild-type mice (msk(+/+)). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk(-/-) and msk(+/+) mice, but reticulocyte count was significantly increased in msk(-/-) mice. Cell membrane PS exposure was similar in untreated msk(-/-) and msk(+/+) erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk(-/-) erythrocytes than in msk(+/+) erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk(-/-) erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk(-/-) mice. The spleens from msk(-/-) mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk(+/+) mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice.

    Original languageEnglish
    Article number17316
    Pages (from-to)1-10
    Number of pages10
    JournalScientific Reports
    Publication statusPublished - 27 Nov 2015


    • Animals
    • Apoptosis
    • Erythrocyte indices
    • Erythrocytes
    • Female
    • Gene expression
    • Hematocrit
    • Hemoglobins
    • Hemolysis
    • Humans
    • Male
    • Mice
    • Mice, Knockout
    • Osmotic fragility
    • Osmotic pressure
    • Phosphatidylserines
    • Primary cell culture
    • Reticulocyte count
    • Ribosomal protein S6 kinases, 90-kDa
    • Journal article
    • Research support, Non-U.S. Gov't


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