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

Wensveen, FM; Geest, CR; Libregts, SF; Derks, IA; Ekert, PG; Labi, V; Villunger, A; Nolte, MA; Eldering, E

Author(s): Wensveen, FM; Geest, CR; Libregts, SF; Derks, IA; Ekert, PG; Labi, V; Villunger, A; Nolte, MA; Eldering, E;
Details: Publication Year 2013-08-23,Volume 18,Issue #11,Page 1306-1318
Journal Title: Apoptosis : An International Journal on Programmed Cell Death
Publication Type: Journal Article
Abstract: 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.
Publisher: Springer
Keywords: Noxa Erythropoiesis ; Apoptosis ; Erythropoietin ; Mcl-1
Research Division(s): Cell Signalling And Cell Death
Publisher's Version: https://doi.org/10.1007/s10495-013-0890-y
Open Access at Publisher's Site: http://rd.springer.com/article/10.1007%2Fs10495-013-0890-y/fulltext.html
Terms of Use/Rights Notice: © Springer, Part of Springer Science+Business Media Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Creation Date: 2013-08-23 12:00:00