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The improved survival of hematopoietic cells cultured with a fusion protein of insulin‐like growth factor II (IGF‐II) and interleukin 3 (IL‐3) is associated with increases in Bcl‐x L and phosphatidylinositol‐3 kinase activity
Author(s) -
DiFalco Marcos R.,
Ali Suhad,
Congote Luis Fernando
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0802396
Subject(s) - biology , propidium iodide , haematopoiesis , interleukin 3 , chimera (genetics) , microbiology and biotechnology , protein kinase b , apoptosis , phosphorylation , immunology , stem cell , t cell , biochemistry , programmed cell death , immune system , interleukin 21 , gene
We compared the antiapoptotic activity of a recombinant chimera of insulin‐like growth factor II (IGF‐II) and interleukin (IL)‐3 with the corresponding equimolar mixture of the individual components based on changes in several factors associated with survival in the CD34+ human hematopoietic cell line TF‐1. Propidium iodide‐stained cells analyzed by fluorescein‐activated cell sorter indicated that the chimera was more effective than the corresponding equimolar mixture in decreasing the amounts of apoptotic cells and increasing the proportion of cells in the S‐phase of the cell cycle. The chimera was more effective in increasing the antiapoptotic protein Bclx L and produced a significant increase in signal transducer and activator of transcription‐5 posphorylation and in phosphatidylinositol‐3 kinase (PI‐3K) activity. The PI‐3K inhibitor LY294002 specifically inhibited cell survival in the presence of the chimera, suggesting a key role of this enzyme in the potentiation of survival caused by the linkage of IGF and IL‐3. This potentiation of survival and its preferential inhibition by LY294002 were also observed in a nontransformed, primary culture of human umbilical cord endothelial cells.