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

作者：Leecharoenkiat Am****; Wannatung Tirawat; Lithanatudom Pathrapol; Svasti Saovaros; Fucharoen Suthat; Chokchaichamnankit Daranee; Srisomsap Chantragan; Smith Duncan R^*

来源：Blood Cells, Molecules, and Diseases, 2011, 47(3): 143-157.

DOI：10.1016/j.bcmd.2011.06.005

Erythropoiesis in beta(0)-thalassaemia/Hb E patients, the most common variant form of p-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 beta(0)-thalassaemia/Hb E erythroblasts and control erythroblasts. The majority of proteins identified as being differentially expressed between beta(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 beta(0-)thalassaemia/Hb E erythroblast differentiation and/or expansion. We propose that increased expansion and differentiation of beta(0)-thalassaemia/Hb E erythroblasts occur as a result of feedback loops acting through increased oxidative metabolism.

• 出版日期2011-10-15