Increased oxidative metabolism is associated with erythroid precursor expansion in β 0-thalassaemia/Hb E disease

• Main Authors: Leecharoenkiat,A., Wannatung,T., Lithanatudom,P., Svasti,S.L., Fucharoen,S., Chokchaichamnankit,D., Srisomsap,C., Smith,D.R.
• Format: Article
• Published: Academic Press Inc. 2015
• Subjects: Cell Biology; Hematology; Molecular Medicine; Molecular Biology
• Online Access: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80053386941&origin=inward; http://cmuir.cmu.ac.th/handle/6653943832/38602
• Institution: Chiang Mai University

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.