Publication: Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/b-thalassemia
Issued Date
2011
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eng
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Mahidol University
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BioMed Central
Bibliographic Citation
Journal of Translational Medicine. Vol. 9, (2011), 96
Suggested Citation
Saranyoo Ponnikorn, Tasanee Panichakul, Kitima Sresanga, Chokdee Wongborisuth, Sittiruk Roytrakul, Suradej Hongeng, Sumalee Tungpradabkul Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/b-thalassemia. Journal of Translational Medicine. Vol. 9, (2011), 96. doi:10.1186/1479-5876-9-96 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/2724
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Title
Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/b-thalassemia
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Abstract
Background: Hemoglobin E/b-thalassemia is particularly common in Southeast Asia and has variable symptoms
ranging from mild to severe anemia. Previous investigations demonstrated the remarkable symptoms of bthalassemia
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/b-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/b-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/b-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/b-thalassemic stem cells is an
effective method to further investigate the cell death mechanism of ineffective erythropoiesis in b-thalassemia. Our
report provides a comprehensive phosphoproteome, an important resource for the study of ineffective
erythropoiesis and developing therapies for HbE/b-thalassemia.