Publication: Increased oxidative metabolism is associated with erythroid precursor expansion in β 0-thalassaemia/Hb E disease
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Issued Date
2011-10-15
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ISSN
10960961
10799796
10799796
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2-s2.0-80053386941
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Mahidol University
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SCOPUS
Bibliographic Citation
Blood Cells, Molecules, and Diseases. Vol.47, No.3 (2011), 143-157
Suggested Citation
Amporn Leecharoenkiat, Tirawat Wannatung, Pathrapol Lithanatudom, Saovaros Svasti, Suthat Fucharoen, Daranee Chokchaichamnankit, Chantragan Srisomsap, Duncan R. Smith Increased oxidative metabolism is associated with erythroid precursor expansion in β 0-thalassaemia/Hb E disease. Blood Cells, Molecules, and Diseases. Vol.47, No.3 (2011), 143-157. doi:10.1016/j.bcmd.2011.06.005 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/11453
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Title
Increased oxidative metabolism is associated with erythroid precursor expansion in β 0-thalassaemia/Hb E disease
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Abstract
Erythropoiesis in β 0 -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 β 0 -thalassaemia/Hb E erythroblasts and control erythroblasts. The majority of proteins identified as being differentially expressed between β 0 -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 β 0 -thalassaemia/Hb E erythroblast differentiation and/or expansion. We propose that increased expansion and differentiation of β 0 -thalassaemia/Hb E erythroblasts occur as a result of feedback loops acting through increased oxidative metabolism. © 2011 Elsevier Inc.