scholarly journals Erythropoietin in Brain Development and Beyond

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Mawadda Alnaeeli ◽  
Li Wang ◽  
Barbora Piknova ◽  
Heather Rogers ◽  
Xiaoxia Li ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Types ◽  
Erythropoietin Receptor ◽  
Adult Brain ◽  
Receptor Expression ◽  
Neural Cells ◽  
Erythroid Progenitor ◽  
Cell Production ◽  
Oxygen Carrying Capacity

Erythropoietin is known as the requisite cytokine for red blood cell production. Its receptor, expressed at a high level on erythroid progenitor/precursor cells, is also found on endothelial, neural, and other cell types. Erythropoietin and erythropoietin receptor expression in the developing and adult brain suggest their possible involvement in neurodevelopment and neuroprotection. During ischemic stress, erythropoietin, which is hypoxia inducible, can contribute to brain homeostasis by increasing red blood cell production to increase the blood oxygen carrying capacity, stimulate nitric oxide production to modulate blood flow and contribute to the neurovascular response, or act directly on neural cells to provide neuroprotection as demonstrated in culture and animal models. Clinical studies of erythropoietin treatment in stroke and other diseases provide insight on safety and potential adverse effects and underscore the potential pleiotropic activity of erythropoietin. Herein, we summarize the roles of EPO and its receptor in the developing and adult brain during health and disease, providing first a brief overview of the well-established EPO biology and signaling, its hypoxic regulation, and role in erythropoiesis.

Role for BH3-Only Protein NOXA In Growth-Factor Deprivation and Early Erythropoiesis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4235-4235
Author(s):  
Christian R. Geest ◽  
Felix M. Wensveen ◽  
Sten F.W.M. Libregts ◽  
Alex M. de Bruin ◽  
Ingrid A.M. Derks ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Erythroid Cell ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Apoptosis Pathway ◽  
Cell Production ◽  
Growth Factor Deprivation ◽  
Redundant Role

Abstract Abstract 4235 Red blood cell production is a strictly regulated process and homeostatic maintenance of the erythropoietic system requires equilibrium between the rate of erythroid cell production and red blood cell destruction. Hematopoietic cytokines play a crucial role in regulating expansion, differentiation and survival of erythrocyte progenitors. Shortage of growth factors triggers the mitochondrial apoptosis pathway, which is critically dependent on Bcl-2 family members. However, the contribution of this mechanism in the regulation of erythropoiesis remains ill-defined. This prompted us to screen for candidate genes involved in this process in erythroid progenitors. We found that the expression of Noxa, a pro-apoptotic Bcl-2 family member, is upregulated during erythroid differentiation and following cytokine-withdrawal in erythroid progenitor cells. Knockdown or deletion of Noxa in IL-3 dependent human and murine erythroid progenitor cell lines increased Mcl-1 levels, which correlated with markedly decreased apoptosis following cytokine withdrawal. Importantly, Noxa ablation in mice increased extra-medullary erythropoiesis, resulting in enhanced numbers of early splenic erythroblasts and circulating reticulocytes. Noxa-deficient hematopoietic progenitors were more resistant to apoptosis induced by growth factor deprivation and displayed increased colony-forming potential. In addition, combined loss of Noxa and Bim resulted in enhanced resistance of erythroid progenitors to cytokine withdrawal compared to WT or single Bim knockouts, suggesting a non-redundant role for Noxa and Bim in regulating survival of erythroid progenitors in response to cytokine deprivation. Finally, in a model of acute haemolytic anaemia, deletion of Noxa enhanced subsequent hematocrit recovery. Together, these findings identify a non-redundant role for BH3-only protein Noxa in the regulation of erythroblast survival during early erythropoiesis. Therefore, Noxa may be a novel component to control red blood cell numbers and modulation of this pathway could be envisaged in therapeutic options for treatment of anaemia. Disclosures: No relevant conflicts of interest to declare.

β-Trcp mediates ubiquitination and degradation of the erythropoietin receptor and controls cell proliferation

Blood ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 5215-5222 ◽  
Author(s):  
Laure Meyer ◽  
Bénédicte Deau ◽  
Hana Forejtníková ◽  
Dominique Duménil ◽  
Florence Margottin-Goguet ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Ubiquitin Proteasome System ◽  
Erythropoietin Receptor ◽  
Serine Residue ◽  
Cell Production ◽  
Ubiquitin Proteasome ◽  
Binding Sequence

Abstract Control of intensity and duration of erythropoietin (Epo) signaling is necessary to tightly regulate red blood cell production. We have recently shown that the ubiquitin/proteasome system plays a major role in the control of Epo-R signaling. Indeed, after Epo stimulation, Epo-R is ubiquitinated and its intracellular part is degraded by the proteasome, preventing further signal transduction. The remaining part of the receptor and associated Epo are internalized and degraded by the lysosomes. We show that β-Trcp is responsible for Epo-R ubiquitination and degradation. After Epo stimulation, β-Trcp binds to the Epo-R. This binding, like Epo-R ubiquitination, requires Jak2 activation. The Epo-R contains a typical DSG binding sequence for β-Trcp that is highly conserved among species. Interestingly, this sequence is located in a region of the Epo-R that is deleted in patients with familial polycythemia. Mutation of the serine residue of this motif to alanine (Epo-RS462A) abolished β-Trcp binding, Epo-R ubiquitination, and degradation. Epo-RS462A activation was prolonged and BaF3 cells expressing this receptor are hypersensitive to Epo, suggesting that part of the hypersensitivity to Epo in familial polycythemia could be the result of the lack of β-Trcp recruitment to the Epo-R.

scholarly journals Oxygen carrying capacity of completely artificial red blood cell substitute : Liposome-embedded-heme

1990 ◽  
Vol 4 (6) ◽  
pp. 676-680
Author(s):  
Koichi Kobayashi ◽  
Masazumi Watanabe ◽  
Toshinori Hashizume ◽  
Masabumi Kawamura ◽  
Ryoichi Kato ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Carrying Capacity ◽  
Oxygen Carrying Capacity

scholarly journals Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells

2016 ◽  
Vol 18 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Felix C. Giani ◽  
Claudia Fiorini ◽  
Aoi Wakabayashi ◽  
Leif S. Ludwig ◽  
Rany M. Salem ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Variation ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Human Genetic Variation ◽  
Cell Production

Lipocalin 2 functions as a negative regulator of red blood cell production in an autocrine fashion

2005 ◽  
Vol 19 (13) ◽  
pp. 1881-1883 ◽  
Author(s):  
Ken‐Ichi Miharada ◽  
Takashi Hiroyama ◽  
Kazuhiro Sudo ◽  
Toshiro Nagasawa ◽  
Yukio Nakamura
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Negative Regulator ◽  
Lipocalin 2 ◽  
Cell Production

scholarly journals Brain spectrin(240/235) and brain spectrin(240/235E): two distinct spectrin subtypes with different locations within mammalian neural cells.

1986 ◽  
Vol 102 (6) ◽  
pp. 2088-2097 ◽  
Author(s):  
B M Riederer ◽  
I S Zagon ◽  
S R Goodman
Keyword(s):  
Blood Cell ◽  
Mouse Brain ◽  
Glial Cells ◽  
Red Blood Cell ◽  
Adult Mouse ◽  
Neuronal Cell ◽  
Neural Cells ◽  
Adult Mouse Brain ◽  
Neuronal Cell Bodies ◽  
Brain Spectrin

Adult mouse brain contains at least two distinct spectrin subtypes, both consisting of 240-kD and 235-kD subunits. Brain spectrin(240/235) is found in neuronal axons, but not dendrites, when immunohistochemistry is performed with antibody raised against brain spectrin isolated from enriched synaptic/axonal membranes. A second spectrin subtype, brain spectrin(240/235E), is exclusively recognized by red blood cell spectrin antibody. Brain spectrin(240/235E) is confined to neuronal cell bodies and dendrites, and some glial cells, but is not present in axons or presynaptic terminals.

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