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1 August 2003 Protective Effects of Thrombopoietin and Stem Cell Factor on X-Irradiated CD34 Megakaryocytic Progenitor Cells from Human Placental and Umbilical Cord Blood
Ikuo Kashiwakura, Osamu Inanami, Kenji Takahashi, Tsuneo A. Takahashi, Mikinori Kuwabara, Yoshinari Takagi
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Abstract

Kashiwakura, I., Inanami, O., Takahashi, K., Takahashi, T. A., Kuwabara, M. and Takagi, Y. Protective Effects of Thrombopoietin and Stem Cell Factor on X-Irradiated CD34 Megakaryocytic Progenitor Cells from Human Placental and Umbilical Cord Blood. Radiat. Res. 160, 210–216 (2003).

In previous studies we characterized the radiosensitivity of CFU-megakaryocytes from human placental and umbilical cord blood and the effects of various early-acting cytokines. We found that the maximal clonal growth of CFU-megakaryocytes in vitro and maximal protection against X-ray damage were supported by a combination of thrombopoietin and stem cell factor. However, the mechanism by which the two cytokines exert a synergistic effect remained unclear, so we extended these studies to investigate the radioprotective action of synergistic thrombopoietin and stem cell factor on the survival of X-irradiated CD34 CFU-megakaryocytes. A combination of thrombopoietin and stem cell factor led to activation of mitogen-activated protein kinase and extracellular signal-regulated protein kinase and to suppression of caspase 3 in X-irradiated CD34 cells. When PD98059 and various synthetic substrates—specific inhibitors of these proteins—were used, the combination had less effect on the clonal growth of X-irradiated CD34 CFU-megakaryocytes. However, the addition of wortmannin, a specific inhibitor of the phosphatidylinositol-3 kinase pathway, did not alter the synergistic action of thrombopoietin plus stem cell factor. We suggest that part of this synergistic effect can be explained by activation of mitogen-activated protein kinase and extracellular signal-regulated protein kinase and by suppression of the caspase cascade.

Ikuo Kashiwakura, Osamu Inanami, Kenji Takahashi, Tsuneo A. Takahashi, Mikinori Kuwabara, and Yoshinari Takagi "Protective Effects of Thrombopoietin and Stem Cell Factor on X-Irradiated CD34 Megakaryocytic Progenitor Cells from Human Placental and Umbilical Cord Blood," Radiation Research 160(2), 210-216, (1 August 2003). https://doi.org/10.1667/3032
Received: 2 August 2002; Accepted: 1 April 2003; Published: 1 August 2003
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