Effects of radiation on the maturation of megakaryocytes.
Effects of radiation on the maturation of megakaryocytes.
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DOI：
10.1093/jrr/rrs127
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发表时间：
2013-05
影响因子：
2
通讯作者：
Kashiwakura I
中科院分区：
文献类型：
--
作者：
Hirose K;Monzen S;Yoshino H;Sato H;Aoki M;Hatayama Y;Kawaguchi H;Sato M;Narita Y;Takai Y;Kashiwakura I
巨核细胞是由巨核细胞祖细胞分化产生的;然而，关于电离辐射如何影响分化途径和细胞反应的信息报道甚少。人白血病K562细胞已被用作研究巨核细胞分化的模型。在本研究中，研究辐射对佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的K562细胞巨核细胞分化的影响，负责表达CD 41抗原（GPIIb/IIIa），据报道，这是在巨核细胞成熟的早期表达的细胞过程进行了分析。4戈伊X射线照射和PMA处理72 h后，CD 41抗原表达明显增加。在该部分中，通过流式细胞术检测到两个群体，CD 41低和CD 41高细胞。CD 41 high细胞维持细胞内ROS在初始水平长达72 h，而CD 41 low细胞在48 h时ROS减少。在PMA刺激后48 h给予N-乙酰半胱氨酸（已知其作为ROS清除剂）时，观察到对CD 41表达的最大抑制作用。当用丝裂原活化蛋白激酶（MAPK）通路抑制剂、ERK 1/2抑制剂和p38 MAPK抑制剂预处理K562细胞，然后用X射线照射和PMA刺激时，两种抑制剂的反应谱显示MAPK通路参与。K562细胞群可能含有至少两种类型的放射敏感性巨核细胞祖细胞的ROS产生机制，细胞内ROS水平决定了CD 41表达的程度。
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, CD41low and CD41high cells, were detected by flow cytometry. The CD41high cells sustained intracellular ROS at the initial level for up to 72 h, but CD41low 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.
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影响因子：
3.1
作者：
Conde, Isabel;Pabon, Dina;Gonzalez-Manchon, Consuelo
通讯作者：
Gonzalez-Manchon, Consuelo
影响因子：
12.4
作者：
Sardina, J. L.;Lopez-Ruano, G.;Hernandez-Hernandez, A.
通讯作者：
Hernandez-Hernandez, A.
影响因子：
20.3
作者：
Dorsey, JF;Cunnick, JM;Wu, J
通讯作者：
Wu, J
影响因子：
64.8
作者：
RUTHERFORD, TR;CLEGG, JB;WEATHERALL, DJ
通讯作者：
WEATHERALL, DJ
影响因子：
3.7
作者：
BURGER, SR;ZUTTER, MM;SANTORO, SA
通讯作者：
SANTORO, SA