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

Authors :
Shuchen Gu
J. Simon C. Arthur
Michael Föller
Teresa F. Ackermann
Madhuri S. Salker
Syed M. Qadri
Kathleen M. S. E. Reyskens
Kashif Jilani
Christine Zelenak
Rosi Bissinger
Yogesh Singh
Elisabeth Lang
Florian Lang
Adrian Lupescu
Erwin Schleicher
Abul Fajol
William P. Sheffield
Mehrdad Ghashghaeinia
Source :
Scientific Reports
Publication Year :
2015
Publisher :
Freie Universität Berlin, 2015.

Abstract

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.

Details

Language :
English
Database :
OpenAIRE
Journal :
Scientific Reports
Accession number :
edsair.doi.dedup.....efe2b41fd3ce5bda3e76667b6c4ad605