BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis

被引:0
作者
Felix M. Wensveen
Christian R. Geest
Sten F. W. M. Libregts
Ingrid A. M. Derks
Paul G. Ekert
Verena Labi
Andreas Villunger
Martijn A. Nolte
Eric Eldering
机构
[1] Academic Medical Center,Department of Experimental Immunology
[2] The Walter and Eliza Hall Institute of Medical Research,Division of Cell Signaling and Cell Death
[3] Innsbruck Medical University,Division of Developmental Immunology, BIOCENTER
[4] Sanquin Research and Landsteiner Laboratory AMC/UvA,Department of Hematopoiesis
来源
Apoptosis | 2013年 / 18卷
关键词
Noxa; Erythropoiesis; Apoptosis; Erythropoietin; Mcl-1;
D O I
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中图分类号
学科分类号
摘要
Apoptosis plays an essential role in the control of erythropoiesis under normal and pathological conditions. However, the contribution of individual proteins within cell death signalling pathways remains poorly defined. Here, we investigated the role of the pro-apoptotic Bcl-2 family member Noxa in the regulation of erythropoiesis. We found that expression of Noxa is induced during erythroid differentiation of human and murine precursor cells. Using in vitro model systems for erythroid progenitors, we observed rapid induction of Noxa upon cytokine deprivation. Knockdown or deletion of Noxa conferred significant protection against apoptosis upon cytokine withdrawal. In vivo, Noxa deficiency did not affect hematological blood parameters or erythroid progenitor composition of bone marrow and spleen under steady-state conditions. In contrast, in a model of acute haemolytic anemia, Noxa-deficiency enhanced hematocrit recovery. Moreover, in a model of chronic inflammation-induced anemia, Noxa-ablation resulted in a dramatic increase of erythroblast expansion. Our data indicate that induction of Noxa in erythroid progenitors sets a survival threshold that limits expansion beyond the number of cells that can be sustained by the available cytokines, which becomes apparent under conditions of induced anemia.
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页码:1306 / 1318
页数:12
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