p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

被引:74
作者
Sardina, J. L.
Lopez-Ruano, G.
Sanchez-Abarca, L. I. [2 ]
Perez-Simon, J. A. [2 ]
Gaztelumendi, A. [3 ]
Trigueros, C. [3 ]
Llanillo, M.
Sanchez-Yaguee, J.
Hernandez-Hernandez, A. [1 ]
机构
[1] Univ Salamanca, Dept Bioquim & Biol Mol, Lab 106, Salamanca 37007, Spain
[2] Hosp Clin Univ Salamanca, Dept Hematol, Salamanca, Spain
[3] Fdn Inbiomed, Fdn Stem Cell Res, Haematopoiet & Mesenchymal Cell Dept, San Sebastian, Spain
关键词
haematopoiesis; megakaryocytic differentiation; NADPH oxidase; p22phox protein; reactive oxygen species; HEMATOPOIETIC STEM-CELLS; CYCLE PROGRESSION; PI3K/AKT PATHWAY; NOX FAMILY; ACTIVATION; EXPRESSION; PROLIFERATION; GROWTH; LINE; CONTRIBUTES;
D O I
10.1038/cdd.2010.67
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transient reactive oxygen species (ROS) production is currently proving to be an important mechanism in the regulation of intracellular signalling, but reports showing the involvement of ROS in important biological processes, such as cell differentiation, are scarce. In this study, we show for the first time that ROS production is required for megakaryocytic differentiation in K562 and HEL cell lines and also in human CD34(+) cells. ROS production is transiently activated during megakaryocytic differentiation, and such production is abolished by the addition of different antioxidants (such as N-acetyl cysteine, trolox, quercetin) or the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. The inhibition of ROS formation hinders differentiation. RNA interference experiments have shown that a p22(phox) dependent NADPH oxidase activity is responsible for ROS production. In addition, the activation of ERK, AKT and JAK2 is required for differentiation, but the activation of phosphatidylinositol 3-kinase and c-Jun N-terminal kinase seems to be less important. When ROS production is prevented, the activation of these signalling pathways is partly inhibited. Taken together, these results show that NADPH oxidase ROS production is essential for complete activation of the main signalling pathways involved in megakaryocytopoiesis to occur. We suggest that this might also be important for in vivo megakaryocytopoiesis. Cell Death and Differentiation (2010) 17, 1842-1854; doi:10.1038/cdd.2010.67; published online 4 June 2010
引用
收藏
页码:1842 / 1854
页数:13
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