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Title: Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/β-thalassemia
Authors: Saranyoo Ponnikorn
Tasanee Panichakul
Kitima Sresanga
Chokdee Wongborisuth
Sittiruk Roytrakul
Suradej Hongeng
Sumalee Tungpradabkul
Mahidol University
Suan Dusit University
Thailand National Center for Genetic Engineering and Biotechnology
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 25-Jun-2011
Citation: Journal of Translational Medicine. Vol.9, No.1 (2011)
Abstract: Background: Hemoglobin E/β-thalassemia is particularly common in Southeast Asia and has variable symptoms ranging from mild to severe anemia. Previous investigations demonstrated the remarkable symptoms of β-thalassemia in terms of the acceleration of apoptotic cell death. Ineffective erythropoiesis has been studied in human hematopoietic stem cells, however the distinct apoptotic mechanism was unclear.Methods: The phosphoproteome of bone marrow HSCs/CD34 + cells from HbE/β-thalassemic patients was analyzed using IMAC phosphoprotein isolation followed by LC-MS/MS detection. Decyder MS software was used to quantitate differentially expressed proteins in 3 patients and 2 normal donors. The differentially expressed proteins from HSCs/CD34 + cells were compared with HbE/β-thalassemia and normal HSCs.Results: A significant change in abundance of 229 phosphoproteins was demonstrated. Importantly, the analysis of the candidate proteins revealed a high abundance of proteins that are commonly found in apoptotic cells including cytochrome C, caspase 6 and apoptosis inducing factors. Moreover, in the HSCs patients a significant increase was observed in a specific type of phosphoserine/threonine binding protein, which is known to act as an important signal mediator for the regulation of cell survival and apoptosis in HbE/β-thalassemia.Conclusions: Our study used a novel method to investigate proteins that influence a particular pathway in a given disease or physiological condition. Ultimately, phosphoproteome profiling in HbE/β-thalassemic stem cells is an effective method to further investigate the cell death mechanism of ineffective erythropoiesis in β-thalassemia. Our report provides a comprehensive phosphoproteome, an important resource for the study of ineffective erythropoiesis and developing therapies for HbE/β-thalassemia. © 2011 Ponnikorn et al; licensee BioMed Central Ltd.
ISSN: 14795876
Appears in Collections:Scopus 2011-2015

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