Artículo
Molecular Mechanisms Involved in Murine Bone Marrow Erythropietic response to Acute Anaemia by Bleeding
Fecha de publicación:
04/2013
Editorial:
Science Alert
Revista:
Journal of of Biological Sciences
ISSN:
1812-5719
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The underlying interactions among apoptosis, erythroid proliferation and differentiation involved in bone marrow erythropoietic response after an acute blood-loss have not yet been elucidated in detail. We hypothesized that Erythropoietin receptor, Bax, caspase-3, cytochrome c, Smac/DIABLO and Bcl-xL molecules play important roles at time of acute erythropoietic need to ameliorate the hypoxic stress. Experiments were performed using in vivo murine model of anaemia induced by blood-loss in a time course study of 15 days. Haematological parameters and bone marrow cellularities were determined. Bone marrow apoptotic assays included: double fluorescent staining (acridine orange/ethidium bromide) and TUNEL. Bone marrow clonogenic assays were performed for evaluating erythroid colony forming unit?s expansion. The Erythropoietin receptor, Bax, Bcl-xL, Smac/DIABLO, caspase-3 and cytochrome c expressions were assessed by immunoblottings. Caspase-3 activity was determined with a colorimetric assay kit. Bleeding induces bone marrow apoptosis from 1 to 3 days, concomitant with Bax over-expression and Bcl-xL decrease. The mitochondrial dysfunction caused cytochrome c and Smac/DIABLO release to cytosol and caspase-3 activation. Erythropoietic recovery was associated with Erythropoietin receptor over expression from the third day, concomitant with the erythroid progenitors and Bcl-xL/Bax ratio enhancements. Erythropoiesis after bleeding depends on a delicate balance among proapoptotic (Bax, caspase-3, cytochrome c, Smac/DIABLO) and prosurvival proteins (Erythropoietin receptor, Bcl-xL), as the crucial regulators in bone marrow erythroid recovery. These findings provide new insights into the homeostatic mechanisms which promote erythropoietic response post-bleeding.
Palabras clave:
Apoptosis
,
Bleeding
,
Bone Marrow
,
Caspase 3
,
Erythropoietin Receptor
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Identificadores
Colecciones
Articulos(CCT - NORDESTE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - NORDESTE
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - NORDESTE
Citación
Todaro, Juan Santiago; Stoyanoff, Tania Romina; Aguirre, María Victoria; Brandan, Nora Cristina; Molecular Mechanisms Involved in Murine Bone Marrow Erythropietic response to Acute Anaemia by Bleeding; Science Alert; Journal of of Biological Sciences; 13; 6; 4-2013; 452-462
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