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-xL and phosphatidylinositol-3 kinase activity.
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 phosphorylation 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.
DiFalco
Marcos R
MR
Department of Medicine, University Health Centre, McGill University, 687 Avenue des Pins, Ouest, Montreal, Quebec, Canada H3A 1A1.
Ali
Suhad
S
Congote
Luis Fernando
LF
D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015398:Signal Transduction; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein; D007335:Insulin-Like Growth Factor II; D019869:Phosphatidylinositol 3-Kinases