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HEME EXPORT AND HEME DEGRADATION DURING MURINE ERYTHROPIESIS
Author(s): ,
Sara Petrillo
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
,
Deborah Chiabrando
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
,
Sonia Mercurio
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
,
Lucia De Franceschi
Affiliations:
Department of Medicine,University of Verona,Verona,Italy
,
Annalisa Camporeale
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
,
Lorenzo Silengo
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
,
Fiorella Altruda
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
Emanuela Tolosano
Affiliations:
Department of Molecular Biotechnology and Health Sciences,University of Turin,Turin,Italy
(Abstract release date: 05/21/15) EHA Library. Petrillo S. 06/12/15; 102733; PB1987 Disclosure(s): University of Turin
University of Turin
Sara Petrillo
Sara Petrillo
Contributions
Abstract
Abstract: PB1987

Type: Publication Only

Background
Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme accumulation within differentiating erythroid cells is crucial for globin genes expression and hemoglobin production. Recently, a role for heme oxygenase (HO)-1and Feline Leukemia Virus subgroup C Receptor (Flvcr)-1 genes in the control of cytosolic heme during erythropoiesis has been reported. HO-1 is the inducible enzyme responsible for heme degradation. Flvcr1 gene encodes for two heme exporters, Flvcr1a and Flvcr1b, localized at the plasma and mitochondrial membrane, respectively. Flvcr1 plays a crucial role in erythropoiesis since loss of both Flvcr1a and Flvcr1b in mice and zebrafish results in anaemia. Moreover, we demonstrated that Flvcr1b is required along all phases of erythropoiesis while Flvcr1a is important for the expansion of committed erythroid precursors but dispensable for their differentiation.

Aims
The aim of this work was the elucidation of the interplay between heme export and heme degradation during erythropoiesis. 

Methods
We isolated erythroid sub-population from murine bone marrow and analyse the expression of Flvcr1 isoforms and HO-1.  Moreover, we compared HO-1 level observed in wild-type mice to that of conditional knock-out mice that do not express Flvcr1a and Flvcr1b in bone marrow. The same analysis was performed on the fetal liver of mouse embryos carrying alleles that differentially affect Flvcr1a and Flvcr1b expression.

Results
Our data indicated different profiles of expression for HO-1, Flvcr1a and Flvcr1b during erythropoiesis. Moreover, when Flvcr1a or Flvcr1b were lost, HO-1 resulted up-regulated.

Summary
These results suggest that during erythroid differentiation, heme export and heme degradation control different pools of heme.

Keyword(s): Erythropoieisis, Heme
Abstract: PB1987

Type: Publication Only

Background
Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme accumulation within differentiating erythroid cells is crucial for globin genes expression and hemoglobin production. Recently, a role for heme oxygenase (HO)-1and Feline Leukemia Virus subgroup C Receptor (Flvcr)-1 genes in the control of cytosolic heme during erythropoiesis has been reported. HO-1 is the inducible enzyme responsible for heme degradation. Flvcr1 gene encodes for two heme exporters, Flvcr1a and Flvcr1b, localized at the plasma and mitochondrial membrane, respectively. Flvcr1 plays a crucial role in erythropoiesis since loss of both Flvcr1a and Flvcr1b in mice and zebrafish results in anaemia. Moreover, we demonstrated that Flvcr1b is required along all phases of erythropoiesis while Flvcr1a is important for the expansion of committed erythroid precursors but dispensable for their differentiation.

Aims
The aim of this work was the elucidation of the interplay between heme export and heme degradation during erythropoiesis. 

Methods
We isolated erythroid sub-population from murine bone marrow and analyse the expression of Flvcr1 isoforms and HO-1.  Moreover, we compared HO-1 level observed in wild-type mice to that of conditional knock-out mice that do not express Flvcr1a and Flvcr1b in bone marrow. The same analysis was performed on the fetal liver of mouse embryos carrying alleles that differentially affect Flvcr1a and Flvcr1b expression.

Results
Our data indicated different profiles of expression for HO-1, Flvcr1a and Flvcr1b during erythropoiesis. Moreover, when Flvcr1a or Flvcr1b were lost, HO-1 resulted up-regulated.

Summary
These results suggest that during erythroid differentiation, heme export and heme degradation control different pools of heme.

Keyword(s): Erythropoieisis, Heme

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