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

被引：46

作者：

Lang, Elisabeth ^{[1
,2
]}

Bissinger, Rosi ^{[1
]}

Fajol, Abul ^{[1
]}

Salker, Madhuri S. ^{[1
]}

Singh, Yogesh ^{[1
]}

Zelenak, Christine ^{[3
]}

Ghashghaeinia, Mehrdad ^{[1
]}

Gu, Shuchen ^{[1
,4
]}

Jilani, Kashif ^{[1
,5
]}

Lupescu, Adrian ^{[1
]}

Reyskens, Kathleen M. S. E. ^{[6
,7
]}

Ackermann, Teresa F. ^{[1
]}

Foeller, Michael ^{[1
,11
]}

Schleicher, Erwin ^{[8
]}

Sheffield, William P. ^{[9
,10
]}

Arthur, J. Simon C. ^{[6
,7
]}

Lang, Florian ^{[1
]}

Qadri, Syed M. ^{[1
,9
,10
]}

机构：

[1] Univ Tubingen, Dept Physiol, D-72076 Tubingen, Germany

[2] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infect Dis, D-40225 Dusseldorf, Germany

[3] Charite, D-10117 Berlin, Germany

[4] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

[5] Univ Agr Faisalabad, Dept Biochem, Faisalabad 38040, Pakistan

[6] Univ Dundee, MRC Phosphorylat Unit, Dundee DD1 5EH, Scotland

[7] Univ Dundee, Div Cell Signaling & Immunol, Coll Life Sci, Dundee DD1 5EH, Scotland

[8] Univ Tubingen, Dept Internal Med, D-72076 Tubingen, Germany

[9] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada

[10] Canadian Blood Serv, Ctr Innovat, Hamilton, ON L8S 4K1, Canada

[11] Univ Halle Wittenberg, Inst Agr & Nutr Sci, D-06120 Halle, Saale, Germany

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

PROGRAMMED CELL-DEATH; NF-KAPPA-B; PHOSPHATIDYLSERINE EXPOSURE; CATION CONDUCTANCE; P38; MAPK; OXIDATIVE STRESS; PHOSPHORYLATION; MEMBRANE; EXPRESSION; CHANNELS;

D O I：

10.1038/srep17316

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 63 条

[11] Phosphatidylserine-related adhesion of human erythrocytes to vascular endothelium [J].

Closse, C ;

Dachary-Prigent, J ;

Boisseau, MR .

BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (02) :300-302

[12] Erythrocytes:: Death of a mummy [J].

Daugas, E ;

Candé, C ;

Kroemer, G .

CELL DEATH AND DIFFERENTIATION, 2001, 8 (12) :1131-1133

[13] Regulation of red cell life-span, erythropoiesis, senescence, and clearance [J].

Diaz, Mario L. .

FRONTIERS IN PHYSIOLOGY, 2014, 5

[14] Functional consequences of sphingomyelinase-induced changes in erythrocyte membrane structure [J].

Dinkla, S. ;

Wessels, K. ;

Verdurmen, W. P. R. ;

Tomelleri, C. ;

Cluitmans, J. C. A. ;

Fransen, J. ;

Fuchs, B. ;

Schiller, J. ;

Joosten, I. ;

Brock, R. ;

Bosman, G. J. C. G. M. .

CELL DEATH & DISEASE, 2012, 3 :e410-e410

[15] Activation of the p38 Map kinase pathway is essential for the antileukemic effects of dasatinib [J].

Dumka, Disha ;

Puri, Poonam ;

Carayol, Nathalie ;

Lumby, Crystal ;

Balachandran, Harikrishnan ;

Schuster, Katja ;

Verma, Amit K. ;

Terada, Lance S. ;

Platanias, Leonidas C. ;

Parmar, Simrit .

LEUKEMIA & LYMPHOMA, 2009, 50 (12) :2017-2029

[16] The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling [J].

Dunn, KL ;

Espino, PS ;

Drobic, B ;

He, SH ;

Davie, JR .

BIOCHEMISTRY AND CELL BIOLOGY, 2005, 83 (01) :1-14

[17] Electrophysiological properties of the plasmodium falciparum-induced cation conductance of human erythrocytes [J].

Duranton, C ;

Huber, SM ;

Tanneur, V ;

Lang, KS ;

Brand, B ;

Sandu, CD ;

Lang, F .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2003, 13 (04) :189-198

[18] Oxidation induces a Cl--dependent cation conductance in human red blood cells [J].

Duranton, C ;

Huber, SM ;

Lang, F .

JOURNAL OF PHYSIOLOGY-LONDON, 2002, 539 (03) :847-855

[19] P38 MAPK and MSK1 mediate caspase-8 activation in manganese-induced mitochondria-dependent cell death [J].

El Mchichi, B. ;

Hadji, A. ;

Vazquez, A. ;

Leca, G. .

CELL DEATH AND DIFFERENTIATION, 2007, 14 (10) :1826-1836

[20] A receptor for phosphatidylserine-specific clearance of apoptotic cells [J].

Fadok, VA ;

Bratton, DL ;

Rose, DM ;

Pearson, A ;

Ezekewitz, RAB ;

Henson, PM .

NATURE, 2000, 405 (6782) :85-90

← 1 2 3 4 5 6 7 →