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http://purl.uniprot.org/citations/16263413http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16263413http://www.w3.org/2000/01/rdf-schema#comment"

Objective

A deficiency of pyruvate kinase (PK) is the most common cause of hereditary nonspherocytic anemia due to glycolytic enzyme defects. Red cells are poorly deformable due to adenosine triphosphate depletion in individuals with a PK deficiency and are destroyed in the microcirculation of the reticuloendothelial system, leading to extravascular hemolysis. The pathophysiology of PK deficiency has been widely studied in PK-deficient mice (PK-1(slc)). We examined the effects of a PK deficiency on erythroid progenitor maturation using these mice.

Materials and methods

The appearance of apoptotic cells in spleen of PK-1(slc) mice was examined by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) staining. We also assayed hematopoietic stem cell colony formation in vitro in the spleen of PK-1(slc) mice, to investigate erythropoiesis, and annexin V binding, as a measure of apoptotic cells in constitutive erythroid colonies, to evaluate the maturation of erythroid progenitors.

Results

The number of hematopoietic progenitors including colony-forming unit erythroids, burst-forming unit erythroids (BFU-E), colony-forming unit granulocyte-macrophages, and multilineage colony-forming units in the spleens of PK-1(slc) was remarkably increased indicating hematopoiesis, and enhanced erythropoiesis in particular. TUNEL assays identified apoptotic cells in the splenic red pulp of the PK-1(slc) mice. Two-color flow cytometry detected apoptotic cells among anti-TER119-positive cells, suggesting that apoptotic cells were of erythroid lineage. Cells undergoing apoptosis were detected in cultures of BFU-E generated from bone marrow cells of PK-1(slc) mice.

Conclusions

The results in this study indicate that the metabolic disturbance in PK deficiency alters not only the survival of red cells but also the maturation of erythroid progenitors, resulting in ineffective erythropoiesis."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.org/dc/terms/identifier"doi:10.1016/j.exphem.2005.07.008"xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Aizawa S."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Harada T."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Fujii H."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Kanno H."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Aisaki K."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Kanbe E."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/author"Tsuboi I."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/name"Exp Hematol"xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/pages"1292-1298"xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/title"Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity."xsd:string
http://purl.uniprot.org/citations/16263413http://purl.uniprot.org/core/volume"33"xsd:string
http://purl.uniprot.org/citations/16263413http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16263413
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