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2-(Trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34 + haematopoietic stem cells

Title
2-(Trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34 + haematopoietic stem cells
Authors
Limb J.-K.Song D.Jeon M.Han S.-Y.Han G.Jhon G.-J.Bae Y.S.Kim J.
Ewha Authors
전길자배윤수한소엽김재상임진경
SCOPUS Author ID
전길자scopus; 배윤수scopus; 한소엽scopus; 김재상scopus; 임진경scopus
Issue Date
2012
Journal Title
Journal of Tissue Engineering and Regenerative Medicine
ISSN
1932-6254JCR Link
Indexed
SCIE; SCOPUS WOS scopus
Abstract
In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34 + haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. © 2012 John Wiley & Sons, Ltd.
DOI
10.1002/term.1628
Appears in Collections:
자연과학대학 > 화학·나노과학전공 > Journal papers
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