Increased oxidative metabolism is associated with erythroid precursor expansion in β0-thalassaemia/Hb E disease
Autor: | Tirawat Wannatung, Pathrapol Lithanatudom, Suthat Fucharoen, Amporn Leecharoenkiat, Duncan R. Smith, Chantragan Srisomsap, Daranee Chokchaichamnankit, Saovaros Svasti |
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Rok vydání: | 2011 |
Předmět: |
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 |
Zdroj: | Blood Cells, Molecules, and Diseases. 47:143-157 |
ISSN: | 1079-9796 |
DOI: | 10.1016/j.bcmd.2011.06.005 |
Popis: | 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. |
Databáze: | OpenAIRE |
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