title: Effects of radiation on the maturation of megakaryocytes.
abstract: Megakaryocytes are generated by the differentiation of megakaryocytic progenitors; however, little information has been reported regarding how ionizing radiation affects the differentiation pathway and cellular responses. Human leukemia K562 cells have been used as a model to study megakaryocytic differentiation. In the present study, to investigate the effects of radiation on phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation of K562 cells, the cellular processes responsible for the expression of CD41 antigen (GPIIb/IIIa), which is reported to be expressed early in megakaryocyte maturation, were analyzed. The expression of CD41 antigens was significantly increased 72 h after treatment with both 4 Gy X-irradiation and PMA. In this fraction, two populations, CD41(low) and CD41(high) cells, were detected by flow cytometry. The CD41(high) cells sustained intracellular ROS at the initial level for up to 72 h, but CD41(low) cells had reduced ROS by 48 h. The maximum suppressive effect on CD41 expression was observed when N-acetyl cysteine, which is known to act as a ROS scavenger, was administered 48 h after PMA stimulation. When K562 cells were pretreated with mitogen-activated protein kinase (MAPK) pathway inhibitors, an ERK1/2 inhibitor and a p38 MAPK inhibitor, followed by X-irradiation and PMA stimulation, the reactivity profiles of both inhibitors showed the involvement of MAPK pathway. There is a possibility that the K562 cell population contains at least two types of radiosensitive megakaryocytic progenitors with respect to ROS production mechanisms, and intracellular ROS levels determine the extent of CD41 expression.
authors.affiliation: Department of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Hirose
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.forename: Hironori
authors.initials: H
authors.lastname: Yoshino
authors.forename: Haruka
authors.initials: H
authors.lastname: Sato
authors.forename: Masahiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Yoshiomi
authors.initials: Y
authors.lastname: Hatayama
authors.forename: Hideo
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Mariko
authors.initials: M
authors.lastname: Sato
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Narita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects*; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
chemical_list: D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate
keywords: K562 cells; MAPK; ROS; megakaryocytopoiesis