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
Rok vydání: 2011
Předmět:
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