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Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/β-thalassemia
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Metadata
Document Title
Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/β-thalassemia
Author
Ponnikorn S.,Panichakul T.,Sresanga K.,Wongborisuth C.,Roytrakul S.,Hongeng S.,Tungpradabkul S.
Name from Authors Collection
Affiliations
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand; Faculty of Science and Technology, Suan Dusit Rajabhat University, Bangkok, Thailand; Research Center, Faculty of Medicine Ramathobodi Hospital, Mahidol University, Bangkok, Thailand; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Type
Article
Source Title
Journal of Translational Medicine
ISSN
14795876
Year
2011
Volume
9
Issue
1
Open Access
All Open Access, Gold, Green
DOI
10.1186/1479-5876-9-96
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.
Keyword
Apoptosis | Hemoglobin E/β-thalassemia | HSCs/CD34+ | Phosphoproteome
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Mahidol University
License
CC BY
Rights
Author
Publication Source
Scopus