المؤلفون: Tirawat Wannatung, Pathrapol Lithanatudom, Suthat Fucharoen, Amporn Leecharoenkiat, Duncan R. Smith, Chantragan Srisomsap, Daranee Chokchaichamnankit, Saovaros Svasti

المصدر: Blood Cells, Molecules, and Diseases. 47:143-157

مصطلحات موضوعية: Adult, Male, Proteomics, Adolescent, Erythroblasts, Cellular differentiation, Blotting, Western, Apoptosis, Biology, medicine.disease_cause, Enzyme activator, Erythroblast, hemic and lymphatic diseases, medicine, Humans, Erythropoiesis, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, Erythroid Precursor Cells, Protein kinase C, U937 cell, Hemoglobin E, beta-Thalassemia, Cell Differentiation, hemic and immune systems, U937 Cells, Cell Biology, Hematology, Middle Aged, Cell biology, Enzyme Activation, Oxidative Stress, Biochemistry, Case-Control Studies, Molecular Medicine, Female, K562 Cells, Reactive Oxygen Species, Glycolysis, Oxidative stress, circulatory and respiratory physiology

الوصف: Erythropoiesis in β0-thalassaemia/Hb E patients, the most common variant form of β-thalassaemia in Southeast Asia, is characterized by accelerated differentiation and over-expansion of erythroid precursor cells. The mechanism driving this accelerated expansion and differentiation remain unknown. To address this issue a proteomic analysis was undertaken to firstly identify proteins differentially expressed during erythroblast differentiation and a second analysis was undertaken to identify proteins differentially expressed between β0-thalassaemia/Hb E erythroblasts and control erythroblasts. The majority of proteins identified as being differentially expressed between β0-thalassaemia/Hb E and control erythroblasts were constituents of the glycolysis/TCA pathway and levels of oxidative stress correlated with the degree of erythroid expansion. A model was constructed linking these observations with previous studies showing increased phosphorylation of ERK1/2 in thalassemic erythroblasts which predicted the increased activation of PKA, PKB and PKC which Western analysis confirmed. Inhibition of PKA or PKC reduced β0-thalassaemia/Hb E erythroblast differentiation and/or expansion. We propose that increased expansion and differentiation of β0-thalassaemia/Hb E erythroblasts occur as a result of feedback loops acting through increased oxidative metabolism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db08af465a458ba506c58e8ca9a07e26Test
https://doi.org/10.1016/j.bcmd.2011.06.005Test

المؤلفون: Saovaros Svasti, Tirawat Wannatung, Amporn Leecharoenkiat, Pathrapol Lithanatudom, Suthat Fucharoen, Duncan R. Smith

المصدر: Annals of Hematology. 90:747-758

مصطلحات موضوعية: Ineffective erythropoiesis, medicine.medical_specialty, Erythroblasts, Cellular differentiation, CD34, Apoptosis, Biology, medicine.disease_cause, Flow cytometry, hemic and lymphatic diseases, Internal medicine, Autophagy, medicine, Humans, Erythropoiesis, Hematology, medicine.diagnostic_test, Hemoglobin E, beta-Thalassemia, Cell Differentiation, hemic and immune systems, General Medicine, Flow Cytometry, Cell biology, Immunology, Calcium, circulatory and respiratory physiology

الوصف: Erythropoiesis in β-thalassemia patients is ineffective, primarily because of death of the erythroid progenitor cells at the polychromatic normoblast stage. While it is known that autophagy plays a critical role during erythropoiesis by removing organelles from erythroid cells during terminal differentiation, its role in erythroid cells whose function is impaired remains to be explored. To investigate this, CD34+ erythroid progenitor cells from normal controls and β-thalassemia/Hb E patients were isolated from peripheral blood and cultured under conditions driving differentiation into an erythroid lineage, and levels of autophagy and apoptosis were analyzed both directly and after biochemical manipulation with L: -asparagine. A significantly higher level of autophagy was seen in β-thalassemia/Hb E erythroblasts as compared to normal control erythroblasts during erythropoiesis. Interestingly, this activation was mediated in part by the presence of high levels of Ca(2+) as modulation of Ca(2+) levels significantly reduced the level of autophagy in these cells. Inhibition of autophagic flux in normal erythroblasts significantly increased apoptosis in normal erythroblasts, but not in thalassemic erythroblasts, although sensitivity to autophagic flux inhibition was restored by reduction of Ca(2+) levels. These results suggest that high levels of autophagy in β-thalassemia/HbE erythroblasts may contribute to the increased levels of apoptosis that lead to ineffective erythropoiesis in β-thalassemia/Hb E erythroblasts.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1f65fef6672d9984d3569c73f143850Test
https://doi.org/10.1007/s00277-010-1152-5Test