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

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...

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Main Authors:	Wensveen, Felix M., Geest, Christian R., Libregts, Sten F. W. M., Derks, Ingrid A. M., Ekert, Paul G., Labi, Verena, Villunger, Andreas, Nolte, Martijn A., Eldering, Eric
Format:	Online
Language:	English
Published:	Springer US 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825139/

id	pubmed-3825139
recordtype	oai_dc
spelling	pubmed-38251392013-11-21 BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis Wensveen, Felix M. Geest, Christian R. Libregts, Sten F. W. M. Derks, Ingrid A. M. Ekert, Paul G. Labi, Verena Villunger, Andreas Nolte, Martijn A. Eldering, Eric Original Paper 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. Springer US 2013-08-23 2013 /pmc/articles/PMC3825139/ /pubmed/23975731 http://dx.doi.org/10.1007/s10495-013-0890-y Text en © The Author(s) 2013 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wensveen, Felix M. Geest, Christian R. Libregts, Sten F. W. M. Derks, Ingrid A. M. Ekert, Paul G. Labi, Verena Villunger, Andreas Nolte, Martijn A. Eldering, Eric
spellingShingle	Wensveen, Felix M. Geest, Christian R. Libregts, Sten F. W. M. Derks, Ingrid A. M. Ekert, Paul G. Labi, Verena Villunger, Andreas Nolte, Martijn A. Eldering, Eric BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
author_facet	Wensveen, Felix M. Geest, Christian R. Libregts, Sten F. W. M. Derks, Ingrid A. M. Ekert, Paul G. Labi, Verena Villunger, Andreas Nolte, Martijn A. Eldering, Eric
author_sort	Wensveen, Felix M.
title	BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
title_short	BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
title_full	BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
title_fullStr	BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
title_full_unstemmed	BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis
title_sort	bh3-only protein noxa contributes to apoptotic control of stress-erythropoiesis
description	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 US
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825139/
_version_	1612025885462888448

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

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