Crucial Role for Endoplasmic Reticulum Stress During Megakaryocyte Maturation

被引:23
作者
Lopez, Jose J. [1 ]
Palazzo, Alberta [2 ]
Chaabane, Chiraz [1 ]
Albarran, Letizia [1 ]
Polidano, Evelyne [1 ]
Lebozec, Kristell [2 ]
Dally, Saoussen [1 ]
Nurden, Paquita [3 ]
Enouf, Jocelyne [1 ]
Debili, Najet [2 ]
Bobe, Regis [1 ]
机构
[1] Univ Paris 11, INSERM, U770, F-94276 Le Kremlin Bicetre, France
[2] Univ Paris 11, Inst Gustave Roussy, INSERM, UMR1009, Villejuif, France
[3] Hop Xavier Arnozan, Ctr Reference Pathol Plaquettaires, Pessac, France
关键词
apoptosis; endoplasmic reticulum stress; platelet; thrombopoiesis; UNFOLDED PROTEIN RESPONSE; ER STRESS; CELL-DIFFERENTIATION; CYTOCHROME-C; ATPASE; 2B; ACTIVATION; EXPRESSION; CA2+; APOPTOSIS; ATF6;
D O I
10.1161/ATVBAHA.113.302184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective Apoptotic-like phase is an essential step for the platelet formation from megakaryocytes. How controlled is this signaling pathway remained poorly understood. The aim of this study was to determine whether endoplasmic reticulum (ER) stress-induced apoptosis occurs during thrombopoiesis. Approach and Results Investigation of ER stress and maturation markers in different models of human thrombopoiesis (CHRF, DAMI, MEG-01 cell lines, and hematopoietic stem cells: CD34(+)) as well as in immature pathological platelets clearly indicated that ER stress occurs transiently during thrombopoiesis. Direct ER stress induction by tunicamycin, an inhibitor of N-glycosylation, or by sarco/endoplasmic reticulum Ca2+ ATPase type 3b overexpression, which interferes with reticular calcium, leads to some degree of maturation in megakaryocytic cell lines. On the contrary, exposure to salubrinal, a phosphatase inhibitor that prevents eukaryotic translation initiation factor 2-P dephosphorylation and inhibits ER stress-induced apoptosis, decreased both expression of maturation markers in MEG-01 and CD34(+) cells as well as numbers of mature megakaryocytes and proplatelet formation in cultured CD34(+) cells. Conclusions Taken as a whole, our research suggests that transient ER stress activation triggers the apoptotic-like phase of the thrombopoiesis process.
引用
收藏
页码:2750 / 2758
页数:9
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