Biological Effects And Signal Transduction Pathways Of Hemangiopoietin In Human Megakarytic Leukemia Cell MO7e

Hemangiopoietin (HAPO) is a novel growth factor that significantly stimulates the proliferation of hematopoietic and endothelial stem/progenitor cells in human and murine systems in vitro. In vivo, subcutaneous injection of rh-HAPO into normal mice could result in a significant increase in bone marrow hematopoietic cells. Furthermore, the irradiated mice given with rh-HAPO had an enhanced survival rate and accelerated hematopoiesis.Our data in the following study further demonstrate that HAPO protects human leukemia cell lines M07e cells from apoptosis induced by growth factor withdrawal. The exact molecular mechanics of HAPO and the intracellular signal transduction pathways were our interests and focus of this study.The cell survival role of protein kinase PI3K and its downstream kinase AKT have been demonstrated in multiple cell lineages and have become the hotpoint of the apoptosis study in recent years. Upon activation by stress, oncogene or cytokines, P13K induces the recruitment of AKT to the cellular membrane as well as AKT phosphorylation. In different study models, activated AKT achieves its survival effects by phosphorylate, blocks the actions of pro-apoptotic Bad (a member of the Bcl-2 family), caspase-9, Forkhead transcriptional factors et al, and alters the activity of a number of other anti-apoptotic mediators, including Bcl-2, Mcl-1, IAPs and NF-κ B, et al.In the present study, human leukemia cell lines M07e was employed as an in vitro study model to investigate the role of the PI3K/AKT pathway in the anti-apoptotic action of HAPO and to examine the possible involvement of apoptotic-associated molecules. The followings were the primary results we have acquired:1) HAPO protects M07e cells from apoptosis induced by growth factor withdrawal through a time and concentration-dependent fashion.2) A substantial increase of PI3K activity and phosphorylation of the kinase AKT were observed after addition of HAPO to growth factor-withdrawal MO7e cells,...